Bio

Clinical Focus


  • Cancer > Lymphoma
  • Cancer > Radiation Oncology
  • Lymphoma
  • Cutaneous Lymphoma
  • Cutaneous Lymphoma - Radiation Oncology
  • Hodgkin's Disease - Radiation Oncology
  • Non-Hodgkin's Lymphoma - Radiation Oncology
  • Mycosis Fungoides - Radiation Oncology
  • Burkitt's Lymphoma - Radiation Oncology
  • Burkitt's Lymphoma
  • Leukemia
  • Leukemia - Radiation Oncology
  • Plasmacytoma
  • Plasmacytoma - Radiation Oncology
  • Radiation Oncology

Professional Education


  • Residency: Stanford University Radiation Oncology Residency (1976) CA
  • Medical Education: Weill Cornell Medical College (1971) NY
  • Board Certification: American Board of Radiology, Radiation Oncology (2016)
  • Internship: Cornell Cooperating Hospitals Northshore and Memorial Hospital (1972) NY
  • Board Certification: American Board of Radiology, Therapeutic Radiology (1976)

Research & Scholarship

Current Research and Scholarly Interests


Irradiation immunosuppression; total body irradiation;, psychosocial effects of cancer treatment; treatment of lymphoma;, mycosis fungoides.

Clinical Trials


  • Combined Blood Stem Cell and Kidney Transplant of One Haplotype Match Living Donor Pairs. Recruiting

    The Stanford Medical Center Program in Multi-Organ Transplantation and the Division of Bone marrow Transplantation are enrolling patients into a research study to determine if donor stem cells given after a living related one Haplotype match kidney transplantation will change the immune system such that immunosuppressive drugs can be completely withdrawn.

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  • Inducing Graft Tolerance in HLA Haplotype Matched Related and 3 Ag Matched Unrelated Living Donor Kidney Transplantation Recruiting

    This research study is to determine if donor blood stem cells given after living, related, HLA antigen (Ag) haplotype match or living, unrelated donor kidney transplantation. Minimal HLA antigen matching will include matching of 2 HLA antigens that can be either HLA A, B, and /or DR. This research will change the immune system such that immunosuppressive drugs can be completely withdrawn or reduced to minimal dose without kidney rejection.

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  • Ph II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma Recruiting

    Non-myeloablative approach for allogeneic transplant is a reasonable option, especially given that the median age at diagnosis is 55-60 years and frequently present compromised skin in these patients, which increases the risk of infection. Therefore, we propose a clinical study with allogeneic HSCT using a unique non-myeloablative preparative regimen, TLI/ATG, to treat advanced MF/SS.

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  • TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas Recruiting

    This phase I trial studies the side effects and best dose of the anti-OX40 antibody BMS-986178 when given together with the TLR9 agonist SD-101 and radiation therapy in treating patients with low-grade B-cell Non-Hodgkin lymphomas. TLR9 agonist SD-101 may stimulate the immune system in different ways and stop cancer cells from growing. Anti-OX40 antibody is a monoclonal antibody that enhances the activation of T cells, immune cells that are important for fighting tumors Radiation therapy uses high energy x-rays to kill cancer cells and may make them more easily detected by the immune system. Giving TLR9 agonist SD-101 together with anti-OX40 antibody BMS 986178 and radiation therapy may work better in treating patients with low-grade B-cell non-hodgkin lymphomas.

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  • A Randomized Phase II Study of Oral Sapacitabine in Patients With Advanced Cutaneous T-cell Lymphoma Not Recruiting

    This is an open label, randomized phase II study designed to evaluate the tolerability and response rate of high-dose and low-dose regimens in patients with advanced cutaneous T-cell lymphoma (CTCL) who have had progressive, recurrent, or persistent disease on or following 2 systemic therapies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Daniel Navi, (650) 736 - 2300.

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  • A Single Agent Phase II Study of Romidepsin (Depsipeptide, FK228) in the Treatment of Cutaneous T-cell Lymphoma (CTCL) Not Recruiting

    GPI-04-0001 was a Phase II, non-randomized, open label, single arm study that was conducted at approximately 30 sites, primarily in the United States, Europe and Russia. It assessed the efficacy, safety, and tolerability of romidepsin as a treatment for cutaneous T-cell lymphoma (CTCL). Study patients (pts) received romidepsin in a dose of 14 mg/m^2 intravenously over 4 hours on Days 1, 8 and 15 of each 28-day cycle. The duration of study treatment was 6 cycles although pts who showed an objective response or stable disease could continue to receive therapy, at the discretion of the investigator, until disease progression or another withdrawal criterion was met.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sunil Arani Reddy, (650) 736 - 1234.

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  • A Study for Patients With Relapsed Cutaneous T-Cell Lymphoma Not Recruiting

    The purpose of the study is to determine the efficacy and safety of enzastaurin in patients with CTCL who failed prior therapies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

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  • Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML Not Recruiting

    Acute myeloid leukemia (AML) is a cancer of the bone marrow that mostly affects older adults. Even with the best chemotherapy, two-year disease-free survival is achieved in a minority of patients. Bone marrow transplantation from a sibling donor may improve cure rates; however, patients over 50 years of age have a high risk of complications and therefore generally are excluded from this treatment option. Recently our group developed a transplantation strategy for older cancer patients that protects against transplant-associated complications, yet does not interfere with the ability of the transplanted donor cells to destroy cancer cells. With this new method, we can now safely evaluate transplantation as a curative therapy for AML patients over the age of 50. We have assembled clinical and scientific researchers throughout the state of California to study and compare bone marrow transplantation using our new approach with the best standard of care chemotherapy in AML patients over the age of 50. The results of this study have the potential to establish a new treatment standard that will improve survival of older AML patients.

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, 650-725-1647.

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  • Allogeneic Transplantation From Related Haploidentical Donors Not Recruiting

    The purpose of the study is to evaluate the feasibility and safety of transplanting CD34+ selected hematopoietic cells from a haploidentical related donor following a nonmyeloablative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG).

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, (650) 723 - 0822.

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  • Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) for Older Patients With Hematologic Malignancies Not Recruiting

    To measure how frequently and to what degree a complication of transplant cell acute graft versus host disease (GvHD) occurs.

    Stanford is currently not accepting patients for this trial. For more information, please contact Physician Referrals, 650-723-0822.

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  • An Open Label Study to Evaluate the Safety and Efficacy of Mechlorethamine(MCH) 0.04% Formulation in Mycosis Fungoides Not Recruiting

    To evaluate the efficacy and safety of topical application of MCH 0.04% in a propylene glycol ointment (PG)in patients with stage I or IIA MF previously treated with MCH 0.02% in a PG or AP ointment who did not achieve a complete response.

    Stanford is currently not accepting patients for this trial. For more information, please contact Kokil Bakshi, (650) 421 - 6370.

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  • Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma Not Recruiting

    The purpose of this trial is to develop an alternative treatment for patients with poor risk non-Hodgkin's lymphoma. This trial uses a combination of high dose chemotherapy with stem cell transplant using the patient's own cells. This is followed with non-myeloablative transplant using stem cells from a related or unrelated donor to try and generate an anti-lymphoma response from the new immune system.

    Stanford is currently not accepting patients for this trial. For more information, please contact Physician Referrals, 650-723-0822.

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  • Brentuximab Vedotin (SGN-35) in Patients With Mycosis Fungoides With Variable CD30 Expression Level Not Recruiting

    The purpose of this study is to learn the effects of brentuximab vedotin (SGN-35), an investigational medication, on patients with cutaneous T cell lymphoma (CTCL), specifically mycosis fungoides (MF) and Sezary syndrome (SS). Despite a wide range of therapeutic options, the treatments are associated with short response duration, thus this condition is largely incurable. This investigational drug may offer less toxicity than standard treatments and have better tumor specific targeting.

    Stanford is currently not accepting patients for this trial. For more information, please contact Kokil Bakshi, 650-421-6370.

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  • Chemotherapy Based on PET Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine, dacarbazine, cyclophosphamide, etoposide, procarbazine hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells. Comparing results of imaging procedures, such as PET scans and CT scans, done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment. PURPOSE: This phase II clinical trial studies how well chemotherapy based on PET/CT scan works in treating patients with stage I or stage II Hodgkin lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Pitsiouni, (650) 721 - 6977.

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  • Combination Chemotherapy Plus Low-Dose Radiation Therapy in Treating Patients With Stage I or Stage IIA Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: This phase 2 trial is studying how well giving combination chemotherapy together with low-dose radiation therapy works in treating patients with stage I or stage IIA Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Anne Wiley, (650) 725 - 6432.

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  • CPG 7909 + Local Radiotherapy in Recurrent Low-Grade Lymphomas Not Recruiting

    Brief summary TBD

    Stanford is currently not accepting patients for this trial. For more information, please contact Cameron Harrison, (650) 721 - 7186.

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  • Extension Study in Subjects Who Relapsed After Complete Response on Study KW-0761-001 Not Recruiting

    This study will enroll subjects with either Peripheral T-Cell Lymphoma (PTCL) or Cutaneous T-Cell Lymphoma(CTCL),including mycosis fungoides (MF) and Sezary Syndrome (SS), who have relapsed after achieving a complete response in study, KW-0761-001.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cutaneous Lymphoma Coordinator, (650) 421 - 6370.

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  • Forodesine in the Treatment of Cutaneous T-Cell Lymphoma Not Recruiting

    This is a Phase II, non-randomized, open-label, single-arm trial that will be conducted at up to 50 sites in North America, Europe and Australia. This study is designed to assess objective response (OR) [complete response (CR) or partial response (PR)] in subjects with cutaneous manifestations of CTCL with a requirement for maintenance of such objective response for at least 28 days in subjects with stage IIB, III, and IVA CTCL. Additionally, this study will evaluate the safety and tolerability of CTCL subjects Stages IB, IIA, IIB, III, or IVA treated with oral forodesine.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

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  • Immunostimulatory CpG SD-101 + RT in Recurrent/Progressive Lymphoma After Allogeneic Hematopoietic Cell Transplantation (HCT) Not Recruiting

    For patients with lymphoma that recurs after chemotherapy, bone marrow transplantation using cells from a healthy donor represents potentially curative treatment. In these individuals, cure is possible because transplantation of healthy donor immune cells can fight the lymphoma in the patient. The goal of this work is to test a strategy that activates the healthy donor immune cells so that they more effectively fight lymphoma and can result in an increased cure rate for these patients. Our group has previously studied CpG, an immune activating medication, in patients with lymphoma and demonstrated modest anti-tumor responses. We now have a more potent form of CpG which we intend to test to see if it will better activate the donor immune cells and result in shrinkage of tumor throughout the entire body, not just at the injected site.

    Stanford is currently not accepting patients for this trial. For more information, please contact Physician Referrals, 650-723-0822.

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  • Lenalidomide in Treating Patients With Relapsed Mycosis Fungoides/Sezary Syndrome Not Recruiting

    RATIONALE: Lenalidomide may stop the growth of mycosis fungoides/Sezary syndrome by blocking blood flow to the cancer. PURPOSE: This phase II trial is studying how well lenalidomide works in treating patients with relapsed mycosis fungoides/Sezary syndrome.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

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  • Low-dose (12 Gy) TSEBT+Vorinostat Versus Low-dose TSEBT Monotherapy in Mycosis Fungoides Not Recruiting

    The purpose of this study is to determine if vorinostat combined with low-dose total skin electron beam therapy (TSEBT) offers superior clinical benefit (efficacy & safety) over low-dose TSEBT alone in participants with mycosis fungoides (MF) Treatment in this study is TSEBT +/- vorinostat, with participants stratified by MF stage.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cutaneous Lymphoma Coordinator, 650-421-6370.

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  • Phase 2 Total Skin Electron Beam Therapy (TSEBT 12 Gy) in Stage IB-IIIA Mycosis Fungoides Not Recruiting

    To examine the efficacy and safety of total skin electron beam therapy to a dose of 12 Gray (TSEBT 12 Gy) in patients who have mycosis fungoides (MF) staged as IB to IIIA.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cameron Harrison, (650) 721 - 7186.

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  • Phase 2 Trial of Prophylactic Rituximab Therapy for Prevention of CGVHD Not Recruiting

    To determine if rituximab administered after allogeneic transplantation decreases the incidence of chronic graft-vs-host disease (cGvHD)

    Stanford is currently not accepting patients for this trial. For more information, please contact Kate Tierney, (650) 725 - 7063.

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  • Phase I/II Study of Intratumoral Injection of CPG 7909, a TLR9 Agonist, Combined With Local Radiation for Patients With Recurrent Mycosis Fungoides. Not Recruiting

    This is a single institution phase I / II trial to evaluate the safety and efficacy of intratumoral CpG injections combined with local radiation in patients with mycosis fungoides. Patients will receive low-dose radiotherapy to a single tumor site on days 1 and 2 (2 Gy each day). CpG injections will be administered into the same tumor site within 24 hours before or 24 hours after each radiation treatment. Weekly doses of (intratumoral or peritumoral injections) CpG will be then administered subcutaneously in the region of previous injections for 23 additional doses. The total treatment duration is 24 weeks.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mayita Romero, (650) 725 - 6452.

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  • Photopheresis as an Interventional Therapy for the Treatment of CTCL (Cutaneous T-Cell Lymphoma, Mycosis Fungoides) Stage 1A, 1B, 2A Not Recruiting

    The study objective is to demonstrate that the UVADEX® Sterile Solution formulation of methoxsalen used in conjunction with the UVAR XTS Photopheresis System can have a clinical effect on the skin manifestations of CTCL (mycosis fungoides) in early stage disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

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  • Pralatrexate and Bexarotene in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma Not Recruiting

    This study is designed to determine the recommended dose, safety, pharmacokinetics, and early efficacy of the combination of pralatrexate plus oral bexarotene in patients with relapsed or refractory CTCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cutaneous Lymphoma Coordinator, (650) 421 - 6370.

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  • Rituximab in Treating Patients With Hodgkin's Lymphoma Not Recruiting

    Phase 2 trial to study the effectiveness of rituximab in treating patients who have lymphocyte-predominant Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Daadi, (650) 725 - 6456.

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  • Rituximab, Bendamustine Hydrochloride, and Bortezomib Followed by Rituximab and Lenalidomide in Treating Older Patients With Previously Untreated Mantle Cell Lymphoma Not Recruiting

    RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma. PURPOSE: This randomized phase II trial studies rituximab, bortezomib, bendamustine, and lenalidomide in treating previously untreated older patients with mantle cell lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ekaterina Dib, 650-723-0503.

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  • Safety and Efficacy of Nitrogen Mustard in Treatment of Mycosis Fungoides Not Recruiting

    This study will evaluate the efficacy, tolerability and safety of the topical application of mechlorethamine (MCH) formulations in patients with stage I or IIA mycosis fungoides (MF).

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

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  • Safety Study to Evaluate Monoclonal Antibody KW-0761 in Subjects With Peripheral T-cell Lymphoma Not Recruiting

    This study will determine the maximum dose of KW-0761 administered intravenously that can be given safely in subjects with previously treated peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma(CTCL)and will see if it is effective in treating the disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Katie Turner, (650) 725 - 1202.

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  • Safety, Pharmacodynamics (PD), Pharmacokinetics (PK) Study of SHP141 in 1A, 1B, or 2A Cutaneous T-Cell Lymphoma (CTCL) Not Recruiting

    The purpose of this study is to investigate the safety and tolerability of topical SHP141 applied directly to skin lesions in patients with Stage IA, IB, or IIA Cutaneous T-cell Lymphoma. This study will also investigate the effect of SHP141 on skin lesions in patients with Stage IA, IB, or IIA CTCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Illisha Rajasansi, 650-421-1397.

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  • Study of Bexxar <Tositumomab> Combined With External Beam Radiation Therapy Not Recruiting

    The purpose of the study is to assess the response rate of patients with relapsed or refractory low-grade or transformed low-grade, CD20-positive, B-cell non-Hodgkin's lymphoma to Iodine-131 (I-131) tositumomab (Bexxar) therapy plus local palliative radiation therapy (XRT).

    Stanford is currently not accepting patients for this trial. For more information, please contact Lucy Schoen, (650) 725 - 1718.

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  • Study of Human Monoclonal Antibody to Treat Mycosis Fungoides and Sezary Syndrome Not Recruiting

    The purpose of this study is to determine the efficacy of the drug, HuMax-CD4, in patients with mycosis fungoides(MF) and sezary syndrome who are intolerant to or do not respond to treatment with Targretin® and one other standard therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Daniel Navi, (650) 736 - 2300.

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  • Study of KW-0761 Versus Vorinostat in Relapsed/Refractory CTCL Not Recruiting

    The purpose of this study is to compare the progression free survival of KW-0761 versus vorinostat for subjects with relapsed or refractory CTCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Illisha Rajasansi, 650-421-1397.

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  • Study of Oral LBH589 in Adult Patients With Refractory/Resistant Cutaneous T-Cell Lymphoma Not Recruiting

    This study will evaluate the safety and efficacy of LBH589B in adult patients with refractory/resistant Cutaneous T-Cell Lymphoma and prior HDAC inhibitor therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

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  • Study of Pralatrexate in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma Not Recruiting

    This study is being conducted to identify how much and how often pralatrexate, given with vitamin B12 and folic acid, can be given safely to patients with cutaneous T-cell lymphoma (CTCL) that has relapsed (returned after responding to previous treatment) or is refractory (has not responded to previous treatment). It is also being conducted to get information on whether or not pralatrexate is effective in treating relapsed or refractory CTCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cameron Harrison, (650) 721 - 7186.

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  • Study of SD-101 in Combination With Localized Low-dose Radiation in Patients With Untreated Low-grade B-cell Lymphoma Not Recruiting

    To assess the safety and tolerability of escalating doses of SD-101 in combination with localized low-dose radiation therapy in adult subjects with untreated low-grade B-cell lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Kathleen McDonald, 650-725-8589.

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  • TLI & ATG for Non-Myeloablative Allogeneic Transplantation for MDS and MPD Not Recruiting

    To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients with advanced stage MDS and MPD.

    Stanford is currently not accepting patients for this trial. For more information, please contact Physician Referrals, 650-723-0822.

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Teaching

2020-21 Courses


Publications

All Publications


  • Hodgkin lymphoma. Nature reviews. Disease primers Connors, J. M., Cozen, W., Steidl, C., Carbone, A., Hoppe, R. T., Flechtner, H., Bartlett, N. L. 2020; 6 (1): 61

    Abstract

    Hodgkin lymphoma (HL) is a B cell lymphoma characterized by few malignant cells and numerous immune effector cells in the tumour microenvironment. The incidence of HL is highest in adolescents and young adults, although HL can affect elderly individuals. Diagnosis is based on histological and immunohistochemical analyses of tissue from a lymph node biopsy; the tissue morphology and antigen expression profile enable classification into one of the four types of classic HL (nodular sclerosis, mixed cellularity, lymphocyte-depleted or lymphocyte-rich HL), which account for the majority of cases, or nodular lymphocyte-predominant HL. Although uncommon, HL remains a crucial test case for progress in cancer treatment. HL was among the first systemic neoplasms shown to be curable with radiation therapy and multiagent chemotherapy. The goal of multimodality therapy is to minimize lifelong residual treatment-associated toxicity while maintaining high levels of effectiveness. Recurrent or refractory disease can be effectively treated or cured with high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation, and prospective trials have demonstrated the potency of immunotherapeutic approaches with antibody-drug conjugates and immune checkpoint inhibitors. This Primer explores the wealth of information that has been assembled to understand HL; these updated observations verify that HL investigation and treatment remain at the leading edge of oncological research.

    View details for DOI 10.1038/s41572-020-0189-6

    View details for PubMedID 32703953

  • Long-term outcomes of patients with unfavorable stage I-II classic Hodgkin lymphoma treated with Stanford V chemotherapy and limited field irradiation. Leukemia & lymphoma Weil, C. R., Qian, Y., Von Eyben, R., Daadi, S. E., Corbelli, K. S., Rosenberg, S. A., Advani, R. H., Hoppe, R. T. 2020: 1–7

    Abstract

    Management of stage I-II unfavorable risk Hodgkin lymphoma (HL) strives to reduce toxicity while maintaining tumor control. Compared to ABVD or BEACOPP, Stanford V chemotherapy contains less doxorubicin and bleomycin. We report long-term outcomes of patients with stage I-II classic HL with European risk factors treated with Stanford V combined modality therapy (CMT). From our institutional cancer registry, we identified 168 patients with ≥1 European risk factor treated with 8-12weeks of Stanford V CMT and consolidative radiotherapy between 1990 and 2016. Outcomes were analyzed after classification by EORTC and GHSG unfavorable criteria. With median follow-up of 8.4years, 10-year overall survival and progression-free survival for the entire cohort were 95% and 88%, respectively. Thirteen of 18 relapses were salvaged successfully. There were no cases of MDS or AML after primary therapy. Long-term outcomes of stage I-II unfavorable risk HL treated with Stanford V CMT are comparable to ABVD or BEACOPP regimens.

    View details for DOI 10.1080/10428194.2020.1768385

    View details for PubMedID 32476541

  • Utility of Routine Surveillance Laboratory Testing in Detecting Relapse in Patients With Classic Hodgkin Lymphoma in First Remission: Results From a Large Single-Institution Study. JCO oncology practice Lynch, R. C., Sundaram, V., Desai, M., Henry, S., Wood, D., Daadi, S., Hoppe, R. T., Advani, R. 2020: JOP1900733

    Abstract

    PURPOSE: Classic Hodgkin lymphoma is highly curable with contemporary therapy. Although the limited role of surveillance imaging to detect early relapse for patients in complete remission at the end of therapy is well established, there is a paucity of data regarding role of laboratory testing in this setting.METHODS: Patients with newly diagnosed classic Hodgkin lymphoma uniformly treated with the Stanford V regimen from 1998-2014 and in complete remission for at least 3 months were identified in a single-center institutional database. Laboratory tests categorized by Common Terminology Criteria for Adverse Events v4.03 as grade 2 or higher were considered abnormal. Primary analysis included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of surveillance laboratory tests for predicting relapse in the first 3 years after end of treatment.RESULTS: Among 235 eligible patients, 24 (10.2%) patients ultimately relapsed. In the first 3 years after end of therapy, the mean number of surveillance blood draws per patient was 7.1, (range, 1-13). These 1,661 surveillance blood draws included 4,684 individual laboratory tests, comprising 1,609 CBCs, 1,578 metabolic panels, and 1,497 erythrocyte sedimentation rates. None of the biopsies confirming relapses were prompted by any abnormal laboratory finding. The sensitivity of any surveillance laboratory test for detecting relapse within 3 years of end of treatment was 72.7% (95% CI, 49.8% to 89.3%), specificity 22.6% (95% CI, 17.2% to 28.9%), yielding a PPV of 8.9% (95% CI, 7.0% to 11.3%) and NPV of 88.9% (95% CI, 79% to 94%).CONCLUSION: Our study found limited clinically meaningful utility for routine surveillance laboratory testing in detecting relapse in patients with complete remission at end of treatment. Our results warrant consideration of modifications to current practice guidelines.

    View details for DOI 10.1200/JOP.19.00733

    View details for PubMedID 32369413

  • Primary Cutaneous Lymphomas Version 2.2020 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Mehta-Shah, N., Horwitz, S. M., Ansell, S., Ai, W. Z., Barnes, J., Berta, S. K., Clemens, M. W., Dogan, A., Fisher, K., Goodman, A. M., Goyal, G., Guitart, J., Halwani, A., Haverkos, B. M., Hoppe, R. T., Jacobsen, E., Jagadeesh, D., Lunning, M. A., Mehta, A., Olsen, E. A., Pro, B., Rajguru, S. A., Shanbhag, S., Shaver, A., Shustov, A., Sokol, L., Torka, P., Torres-Cabala, C., Wilcox, R., William, B. M., Zain, J., Dwyer, M. A., Sundar, H., Kim, Y. H. 2020; 18 (5): 523–36

    Abstract

    Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL), and Sézary syndrome (SS) is a rare erythrodermic and leukemic subtype of CTCL characterized by significant blood involvement. Although early-stage disease can be effectively treated predominantly with skin-directed therapies, systemic therapy is often necessary for the treatment of advanced-stage disease. Systemic therapy options have evolved in recent years with the approval of novel agents such as romidepsin, brentuximab vedotin, and mogamulizumab. These NCCN Guidelines Insights discuss the diagnosis and management of MF and SS (with a focus on systemic therapy).

    View details for DOI 10.6004/jnccn.2020.0022

    View details for Web of Science ID 000531161900007

    View details for PubMedID 32380458

  • Mixed chimerism and acceptance of kidney transplants after immunosuppressive drug withdrawal. Science translational medicine Busque, S., Scandling, J. D., Lowsky, R., Shizuru, J., Jensen, K., Waters, J., Wu, H. H., Sheehan, K., Shori, A., Choi, O., Pham, T., Fernandez Vina, M. A., Hoppe, R., Tamaresis, J., Lavori, P., Engleman, E. G., Meyer, E., Strober, S. 2020; 12 (528)

    Abstract

    Preclinical studies have shown that persistent mixed chimerism is linked to acceptance of organ allografts without immunosuppressive (IS) drugs. Mixed chimerism refers to continued mixing of donor and recipient hematopoietic cells in recipient tissues after transplantation of donor cells. To determine whether persistent mixed chimerism and tolerance can be established in patients undergoing living donor kidney transplantation, we infused allograft recipients with donor T cells and hematopoietic progenitors after posttransplant lymphoid irradiation. In 24 of 29 fully human leukocyte antigen (HLA)-matched patients who had persistent mixed chimerism for at least 6 months, complete IS drug withdrawal was achieved without subsequent evidence of rejection for at least 2 years. In 10 of 22 HLA haplotype-matched patients with persistent mixed chimerism for at least 12 months, reduction of IS drugs to tacrolimus monotherapy was achieved. Withdrawal of tacrolimus during the second year resulted in loss of detectable chimerism and subsequent rejection episodes, unless tacrolimus therapy was reinstituted. Posttransplant immune reconstitution of naïve B cells and B cell precursors was more rapid than the reconstitution of naïve T cells and thymic T cell precursors. Robust chimerism was observed only among naïve T and B cells but not among memory T cells. No evidence of rejection was observed in all surveillance graft biopsies obtained from mixed chimeric patients withdrawn from IS drugs, and none developed graft-versus-host disease. In conclusion, persistent mixed chimerism established in fully HLA- or haplotype-matched patients allowed for complete or partial IS drug withdrawal without rejection.

    View details for DOI 10.1126/scitranslmed.aax8863

    View details for PubMedID 31996467

  • Eli J. Glatstein: A Steward Extraordinaire of Radiation Oncology. International journal of radiation oncology, biology, physics Coleman, C. N., Hoppe, R. T., Metz, J. M. 2020; 107 (1): 1–5

    View details for DOI 10.1016/j.ijrobp.2020.01.016

    View details for PubMedID 32277912

  • Long-Term Outcomes in 10-Year Survivors of Early-Stage Hodgkin Lymphoma. International journal of radiation oncology, biology, physics Bates, J. E., Parikh, R. R., Mendenhall, N. P., Morris, C. G., Hoppe, R. T., Constine, L. S., Hoppe, B. S. 2020

    Abstract

    Although radiotherapy improves progression-free survival in early-stage HL, substantial concerns remain regarding delayed normal tissue effects impacting quality of life and survival. We hypothesized that treatment with combined-modality therapy (CMT, chemotherapy and radiotherapy) improves overall survival among 10-year survivors when compared to treatment with radiotherapy or chemotherapy alone.We compared patients in the SEER database diagnosed with stage I/II Hodgkin lymphoma between 1983 and 2006 who received chemotherapy and/or external-beam radiation and survived at least 10 years. Our primary study outcome was overall survival; we additionally analyzed cause-specific and other-cause-specific survival.Of 10,443 10-year survivors of stage I/II classical Hodgkin lymphoma, 33.6% received chemotherapy alone, 23.8% radiotherapy alone, and 42.6% CMT. Median follow-up was 16.1 years. On multivariate analysis including race, stage, gender, age, and "modern" treatment in 1995+, 10-year survivors who received CMT had improved overall survival relative to survivors who received RT alone (HR=1.41, 95% CI=1.21-1.64, p<0.01) or chemotherapy alone (HR=1.35, 95% CI=1.16-1.57, p<0.01).This survival difference was driven by an increase in death due to both HL and non-HL causes in those treated with chemotherapy alone. Our analysis suggests that CMT offers optimal survivorship for patients with stage I/II Hodgkin lymphoma.

    View details for DOI 10.1016/j.ijrobp.2020.02.642

    View details for PubMedID 32173399

  • Hodgkin Lymphoma, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Hoppe, R. T., Advani, R. H., Ai, W. Z., Ambinder, R. F., Armand, P., Bello, C. M., Benitez, C. M., Bierman, P. J., Boughan, K. M., Dabaja, B., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Herrera, A. F., Hochberg, E. P., Huang, J., Johnston, P. B., Kaminski, M. S., Kenkre, V. P., Khan, N., Lynch, R. C., Maddocks, K., McConathy, J., McKinney, M., Metzger, M., Morgan, D., Mulroney, C., Rabinovitch, R., Rosenspire, K. C., Seropian, S., Tao, R., Winter, J. N., Yahalom, J., Burns, J. L., Ogba, N. 2020; 18 (6): 755–81

    Abstract

    The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. Current management of classic HL involves initial treatment with chemotherapy alone or combined modality therapy followed by restaging with PET/CT to assess treatment response. Overall, the introduction of less toxic and more effective regimens has significantly advanced HL cure rates. This portion of the NCCN Guidelines focuses on the management of classic HL.

    View details for DOI 10.6004/jnccn.2020.0026

    View details for PubMedID 32502987

  • Nonmyeloablative allogeneic transplantation achieves clinical and molecular remission in cutaneous T-cell lymphoma. Blood advances Weng, W. K., Arai, S., Rezvani, A., Johnston, L., Lowsky, R., Miklos, D., Shizuru, J., Muffly, L., Meyer, E., Negrin, R. S., Wang, E., Almazan, T., Million, L., Khodadoust, M., Li, S., Hoppe, R. T., Kim, Y. H. 2020; 4 (18): 4474–82

    Abstract

    The majority of patients with refractory, advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) have a life expectancy of <5 years. Here, we report a phase 2 study of a novel nonmyeloablative allogeneic transplantation strategy tailored for this patient population. This study has completed the enrollment, and 35 patients (13 MF, 22 SS) have undergone transplant as planned. The majority (80%) of the patients had stage IV disease and received multiple previous systemic therapies. All patients had active disease at the time of conditioning using total skin electron beam therapy, total lymphoid irradiation, and antithymocyte globulin, and received allograft infusion as outpatients. Cyclosporine or tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. Patients tolerated the transplant well, with 1- and 2-year nonrelapse mortality of 3% and 14%, respectively. The day +180 cumulative incidence of grade 2 to 4 acute GVHD was 16%, and the 2-year incidence of moderate/severe chronic GVHD was 32%. With a median posttransplant follow-up of 5.4 years, the 2-, 3-, and 5-year overall survival rates were 68%, 62%, and 56%. Using high-throughput sequencing of the T-cell receptor for minimal residual disease monitoring, we observed that 43% achieved molecular remission, which was associated with a lower incidence of disease progression or relapse (9% vs 87%; P = .02). Our study also showed that patients who were aged ≥65 years at the time of allotransplant had similar clinical outcomes compared with younger patients. Thus, we have developed an alternative and potentially curative nonmyeloablative allogeneic transplant regimen for patients with advanced stage MF/SS. This trial was registered at www.clinicaltrials.gov as #NCT00896493.

    View details for DOI 10.1182/bloodadvances.2020001627

    View details for PubMedID 32941647

  • A preliminary report of gonadal-sparing TBI using a VMAT technique. Practical radiation oncology Blomain, E. S., Kovalchuk, N., Neilsen, E., Skinner, L., Hoppe, R. T., Hiniker, S. M. 2020

    Abstract

    Reproductive toxicity is common following total body irradiation and has major quality of life implications for patients. In that context, this is the first report of gonadal-sparing VMAT TBI, successfully delivered in a boy and a girl with aplastic anemia. Both patients' VMAT TBI plans demonstrated improved gonadal sparing versus simulated conventional 2D approach (mean testes dose 0.45 Gy VMAT versus 0.72 Gy 2D; mean ovary dose 0.64 Gy VMAT versus 1.47 Gy 2D). PTV coverage was also improved for both cases with the VMAT plan versus conventional 2D plan (2 Gy D90% versus 1.9 Gy D90%, respectively). Given these dosimetric advantages, the present study can serve as a proof-of-concept for further prospective studies evaluating this technique for wider applications in populations receiving TBI.

    View details for DOI 10.1016/j.prro.2020.07.006

    View details for PubMedID 32795616

  • Stage I-II Nodular Lymphocyte-Predominant Hodgkin Lymphoma: a Multi-institutional Experience of Adult Patients by ILROG. Blood Binkley, M. S., Rauf, M. S., Milgrom, S. A., Pinnix, C. C., Tsang, R. W., Dickinson, M., Ng, A., Roberts, K. B., Gao, S., Balogh, A. G., Ricardi, U., Levis, M., Casulo, C., Stolten, M., Specht, L., Plastaras, J. P., Wright, C., Kelsey, C. R., Brady, J. L., Mikhaeel, N. G., Hoppe, B. S., Terezakis, S., Picardi, M., Della Pepa, R., Kirova, Y., Akhtar, S., Maghfoor, I., Koenig, J. L., Jackson, C., Song, E., Sehgal, S., Advani, R., Natkunam, Y., Constine, L. S., Eich, H. T., Wirth, A., Hoppe, R. T. 2020

    Abstract

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment for stage I-II NLPHL is undefined. We conducted a multi-center retrospective study including patients ≥16 years with stage I-II NLPHL diagnosed from 1995-2018 receiving all forms of management including radiotherapy (RT), combined modality therapy (CMT=RT+chemotherapy), chemotherapy (CT), observation after excision, rituximab and RT, and single agent rituximab (R). End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age 39 years, 72.3% being male, and 54.9% having stage I disease. Median follow up was 5.5 years (IQR=3.1-10.1). 5-year PFS and OS for the entire cohort were 87.1% (95%CI=83.6-90.0%) and 98.3% (95%CI=96.4-99.2%), respectively. Primary management was RT alone (n=257, 46.0%), CMT (n=184, 32.9%), CT alone (n=47, 8.4%), observation (n=37, 6.6%), rituximab and RT (n=19, 3.4%), and rituximab alone (n=15, 2.7%). 5-year PFS rates were 91.1% (95%CI=85.3-94.7%) after RT, 90.5% (95%CI=84.8-94.1%) after CMT, 77.8% (95%CI=61.3-88.0%) after chemotherapy, 73.5% (95%CI=50.6-87.0%) after observation, 80.8% (95%CI=41.0-95.1%) after rituximab and RT, and 38.5% (95%CI=14.0-62.8%) after rituximab alone. For the RT cohort but not the CMT cohort, variant immunoarchitectural pattern and number of sites>2 were associated with worse PFS (P<0.05). Overall, 21 patients (3.8%) developed large cell transformation, with a significantly higher transformation rate for those with variant immunoarchitectural pattern (P=0.049) and number of involved sites >2 (P=0.0006). OS for patients with stage I-II NLPHLwas excellent following all managements.

    View details for DOI 10.1182/blood.2019003877

    View details for PubMedID 32211877

  • Keep the Dose Low. Keep the Fields Tight. International journal of radiation oncology, biology, physics Hoppe, R. T. 2020; 106 (1): 15

    View details for DOI 10.1016/j.ijrobp.2018.04.022

    View details for PubMedID 31836076

  • The Meaningless Meaning of Mean Heart Dose in Mediastinal Lymphoma in the Modern Radiotherapy Era. Practical radiation oncology Hoppe, B. S., Bates, J. E., Mendenhall, N. P., Morris, C. G., Louis, D., Ho, M. W., Hoppe, R., Shaikh, M., L, Z., Flampouri, S. 2019

    Abstract

    BACKGROUND & PURPOSE: Mean heart dose (MHD) correlates with late cardiac toxicity among survivors of lymphoma receiving involved-field radiotherapy (IFRT). We investigated MHD and cardiac substructure dose across older and newer radiation fields and techniques to understand the value of evaluating MHD alone.PATIENTS & METHODS: Following IRB approval, we developed a database of dosimetry plans for 40 mediastinal lymphoma patients, which included IFRT (AP/PA), involved-site radiotherapy (ISRT) + 3-dimensional conformal radiotherapy (3DCRT), ISRT + intensity-modulated radiotherapy (IMRT), and ISRT + proton therapy plans for each patient. Each plan was evaluated for dose to the heart and cardiac substructures, including the right and left ventricles (RV, LV) and atria (RA, LA); tricuspid, mitral, and aortic valves (TV, MV, AV); and left anterior descending coronary artery (LAD). Correlation between MHD and cardiac substructure dose was assessed with linear regression. A correlation was considered very strong, strong, moderate, or weak if the r was > 0.8, 0.6-0.79, 0.4-0.59, and <0.4, respectively.RESULTS: A strong correlation was observed between MHD and the mean cardiac substructure dose for each plan as follows: IFRT-LV, RV, and LAD; ISRT+3DCRT-LV, RV, and LA; ISRT+IMRT-LV and RV; ISRT+proton therapy-none. The following moderate correlations were observed: IFRT-LA and MV; ISRT+3DCRT-LAD, MV, and TV; ISRT+IMRT-LA, LAD, and MV; ISRT+proton therapy-LV only.CONCLUSIONS: In the management of mediastinal lymphoma, more conformal treatment techniques can lead to more heterogeneous dose distributions across the heart, which translate into weaker relationships between mean heart dose and mean cardiac substructure doses. Consequently, models for assessing the risk of cardiac toxicity after radiotherapy that rely on MHD can be misleading when using modern treatment fields and techniques.

    View details for DOI 10.1016/j.prro.2019.09.015

    View details for PubMedID 31586483

  • Role of imaging in low-grade cutaneous B-cell lymphoma presenting in the skin JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Kheterpal, M. K., Dai, J., Geller, S., Pulitzer, M., Ni, A., Myskowski, P. L., Moskowitz, A., Kim, J., Hong, E. K., Fong, S., Hoppe, R. T., Kim, Y. H., Horwitz, S. M. 2019; 81 (4): 970–76
  • Tomayto, tomahto: prescription dose and mean heart dose in evaluating the cardiac impact of involved-field radiation therapy for Hodgkin lymphoma survivors ACTA ONCOLOGICA Bates, J. E., Flampouri, S., Hoppe, R. T., Li, Z., Mendenhall, N. P., Hoppe, B. S. 2019
  • Volumetric Modulated Arc Therapy and 3-Dimensional Printed Bolus in the Treatment of Refractory Primary Cutaneous Gamma Delta Lymphoma of the Bilateral Legs PRACTICAL RADIATION ONCOLOGY Obeid, J., Gutkin, P. M., Lewis, J., Skinner, L., Wang, E. B., Khodadoust, M. S., Kim, Y. H., Weng, W., Hoppe, R. T., Hiniker, S. M. 2019; 9 (4): 220–25
  • Salvage Treatment and Survival for Relapsed Follicular Lymphoma Following Primary Radiation Therapy: A Collaborative Study on Behalf of ILROG INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Binkley, M. S., Brady, J. L., Hajj, C., Chelius, M., Chau, K., Balogh, A., Levis, M., Filippi, A., Jones, M., Ahmed, S., MacManus, M., Wirth, A., Oguchi, M., Vistisen, A., Andraos, T., Ng, A. K., Aleman, B. P., Choi, S., Kirova, Y. M., Hardy, S., Reinartz, G., Eich, H. T., Bratman, S., Constine, L. S., Suh, C., Dabaja, B., El-Galaly, T. C., Hodgson, D. C., Ricardi, U., Yahalom, J., Mikhaeel, G., Hoppe, R. T. 2019; 104 (3): 522–29
  • Low-dose Total Skin Electron Beam Therapy for Refractory Cutaneous CD30 Positive Lymphoproliferative Disorders. The Journal of dermatological treatment Panjwani, N., Yoo, C. H., Wang, E., Khodadoust, M. S., Kim, Y. H., Hoppe, R. T., Hiniker, S. M. 2019: 1–5

    Abstract

    We describe a case of a 48-year-old woman with a refractory cutaneous CD30 positive lymphoproliferative disorder treated successfully with total skin electron beam radiotherapy (TSEBT).

    View details for DOI 10.1080/09546634.2019.1628913

    View details for PubMedID 31179774

  • Salvage treatment and survival for relapsed follicular lymphoma following primary radiotherapy: A collaborative study on behalf of ILROG. International journal of radiation oncology, biology, physics Binkley, M. S., Brady, J. L., Hajj, C., Chelius, M., Chau, K., Balogh, A., Levis, M., Filippi, A. R., Jones, M., Ahmed, S., MacManus, M., Wirth, A., Oguchi, M., Vistisen, A. K., Andraos, T. Y., Ng, A., Aleman, B. M., Choi, S. H., Kirova, Y., Hardy, S., Reinartz, G., Eich, H., Bratman, S., Constine, L. S., Suh, C., Dabaja, B., El-Galaly, T., Hodgson, D., Ricardi, U., Yahalom, J., Mikhaeel, N. G., Hoppe, R. T. 2019

    Abstract

    PURPOSE/OBJECTIVE(S): We previously reported 30% of patients with localized follicular lymphoma (FL) staged by 18F-FDG-PET-CT (PET-CT) receiving primary radiotherapy (RT) will relapse within 5 years. We sought to report outcomes for those who relapsed.MATERIALS/METHODS: We conducted a multicenter retrospective study of patients who received RT≥24Gy for stage I-II FL grade 1-3A FL, with age≥18 years, and PET-CT staging. Observation was defined as >6 months without treatment from relapse. Overall survival (OS) and freedom from progression (FFP) were estimated with Kaplan-Meier, and uni- and multivariable analyses (MVA) with Cox regression.RESULTS: Of 512 patients with median follow up of 52 months, 149 (29.1%) developed recurrent lymphoma at a median 23 months (range, 1-143) after primary RT. Median follow up was 33 months post relapse. 3-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ≤12 months from date of diagnosis versus all others, 88.7% versus 95.8%, respectively (p=0.01), and remained significantly worse on MVA (FLIPI-adjusted HR=3.61, p=0.009). Histology at relapse included: 93 indolent (grade 1-3A), 3 FL grade 3B/NOS, 18 diffuse large B-cell lymphoma (DLBCL); 35 patients were not biopsied. Of those with follow up ≥3 months and biopsied (n=74) or presumed (n=23) indolent recurrence, 58 patients (59.8%) were observed, 19 (19.6%) had systemic therapy, 16 (16.5%) RT, and 4 (4.1%) systemic therapy+RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n=59, including 20 initially observed) 3-year FFP was 73.9%.CONCLUSIONS: Prognosis for patients with relapsed FL following primary radiotherapy is excellent supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (<12 months) have inferior survival to those with longer disease-free interval.

    View details for PubMedID 30858143

  • Volumetric modulated arc therapy and 3-dimensional printed bolus in the treatment of refractory primary cutaneous gamma delta lymphoma of the bilateral legs. Practical radiation oncology Obeid, J., Gutkin, P. M., Lewis, J., Skinner, L., Wang, E. B., Khodadoust, M. S., Kim, Y. H., Weng, W., Hoppe, R. T., Hiniker, S. M. 2019

    Abstract

    Patients with extensive dermal and subcutaneous disease present a technical challenge for treatment with radiation therapy (RT). Volumetric arc therapy (VMAT) can effectively treat disease on circumferential surfaces while minimizing dose to the core structures. However, treatment of extensive areas of the bilateral lower extremities with this technique has not been previously reported. Here we report the successful treatment of a patient with primary cutaneous gamma-delta T-cell lymphoma of the bilateral legs using VMAT and a custom 3-dimensional printed bolus. This approach is applicable for the treatment of cutaneous malignancies of the lower extremities.

    View details for PubMedID 30836188

  • Definitive radiotherapy for localized follicular lymphoma staged by F-18-FDG PET-CT: a collaborative study by ILROG BLOOD Brady, J. L., Binkley, M. S., Hajj, C., Chelius, M., Chau, K., Balogh, A., Levis, M., Filippi, A., Jones, M., Mac Manus, M., Wirth, A., Oguchi, M., Vistisen, A., Andraos, T., Ng, A. K., Aleman, B. P., Choi, S., Kirova, Y., Hardy, S., Reinartz, G., Eich, H. T., Bratman, S. V., Constine, L. S., Suh, C., Dabaja, B., El-Galaly, T. C., Hodgson, D. C., Ricardi, U., Yahalom, J., Hoppe, R. T., Mikhaeel, G. 2019; 133 (3): 237–45
  • Larry Emanuel Kun, March 10, 1946-May 27, 2018. International journal of radiation oncology, biology, physics FitzGerald, T. J., Donaldson, S. S., Wharam, M., Laurie, F., Bishop-Jodoin, M., Moni, J., Tarbell, N., Shulkin, B., McCarville, E., Merchant, T., Krasin, M., Wolden, S., Halperin, E., Constine, L. S., Haas-Kogan, D., Marcus, K., Freeman, C., Wilson, J. F., Hoppe, R., Cox, J., Terezakis, S., Million, L., Smith, M. A., Mendenhall, N. P., Marcus, R. B., Cherlow, J., Kalapurakal, J., Breneman, J., Yock, T., MacDonald, S., Laack, N., Donahue, B., Indelicato, D., Michalski, J., Perkins, S., Kachnic, L., Choy, H., Braunstein, S., Esiashvilli, N., Roberts, K. B. 2019; 103 (1): 8–14

    View details for PubMedID 30563668

  • 20 Gy Versus 30 Gy: Will it Make a Difference? International journal of radiation oncology, biology, physics Hoppe, R. T. 2019; 105 (1): 102–3

    View details for DOI 10.1016/j.ijrobp.2019.06.008

    View details for PubMedID 31422803

  • Nonmyeloablative TLI-ATG conditioning for allogeneic transplantation: mature follow-up from a large single-center cohort. Blood advances Spinner, M. A., Kennedy, V. E., Tamaresis, J. S., Lavori, P. W., Arai, S., Johnston, L. J., Meyer, E. H., Miklos, D. B., Muffly, L. S., Negrin, R. S., Rezvani, A. R., Shizuru, J. A., Weng, W. K., Hoppe, R. T., Strober, S., Lowsky, R. 2019; 3 (16): 2454–64

    Abstract

    Nonmyeloablative total lymphoid irradiation and antithymocyte globulin (TLI-ATG) conditioning is protective against graft-versus-host disease (GVHD), while retaining graft-versus-tumor activity across various hematologic malignancies. We report our comprehensive experience using TLI-ATG conditioning in 612 patients with hematologic malignancies who underwent allogeneic transplantation at Stanford University from 2001 to 2016. All patients received granulocyte colony-stimulating factor-mobilized peripheral blood grafts and cyclosporine and mycophenolate mofetil for GVHD prophylaxis. The median age was 60 years (range, 21-78), with a median follow-up of 6.0 years (range, 1.0-16.4). Common diagnoses included acute myeloid leukemia (AML; n = 193), myelodysplastic syndrome (MDS; n = 94), chronic lymphocytic leukemia (CLL; n = 80), non-Hodgkin lymphoma (NHL; n = 175), and Hodgkin lymphoma (HL; n = 35). Thirty-four percent of patients had a comorbidity index ≥3, 30% had a high to very high disease risk index, and 56% received unrelated donor grafts, including 15% with HLA-mismatched donors. Ninety-eight percent underwent transplant in the outpatient setting, and 57% were never hospitalized from days 0 through 100. The 1-year rates of nonrelapse mortality (NRM), grade II-IV acute GVHD, and extensive chronic GVHD were 9%, 14%, and 22%, respectively. The 4-year estimates for overall and progression-free survival were 42% and 32% for AML, 30% and 21% for MDS, 67% and 43% for CLL, 68% and 45% for NHL, and 78% and 49% for HL. Mixed chimerism correlated with the risk of relapse. TLI-ATG conditioning was well tolerated, with low rates of GVHD and NRM. Durable remissions were observed across hematologic malignancies, with particularly favorable outcomes for heavily pretreated lymphomas. Several efforts are underway to augment donor chimerism and reduce relapse rates while maintaining the favorable safety and tolerability profile of this regimen.

    View details for DOI 10.1182/bloodadvances.2019000297

    View details for PubMedID 31427277

  • Role of imaging in low grade cutaneous B-cell lymphoma presenting in the skin. Journal of the American Academy of Dermatology Kheterpal, M. K., Dai, J., Geller, S., Pulitzer, M., Ni, A., Myskowski, P. L., Moskowitz, A., Kim, J., Hong, E. K., Fong, S., Hoppe, R. T., Kim, Y. H., Horwitz, S. M. 2019

    Abstract

    Whole body imaging is current standard of care for staging all patients presenting with skin lesion(s) of B-cell lymphomas (BCL), regardless of skin disease extent, however supporting data are lacking.To determine the clinical utility of imaging in detection of systemic involvement in low grade cutaneous B-cell lymphoma presenting in the skin.Retrospective cohort analysis of patients presenting with cutaneous lesions of BCLs at Memorial Sloan Kettering Cancer Center (MSKCC) and Stanford University (SU) from 1997-2016.At initial staging, of the 522 patients (306 marginal zone and 216 follicle-center cell histology), extracutaneous disease was noted in 3.6% and 8.8% of patients with MZL and FCL histology respectively. In patients with systemic involvement, imaging alone identified 81.8% (9/11) of MZL and 89.4% of follicular lymphoma (FL) cases. In primary cutaneous MZL (pc-MZL) and primary cutaneous follicle center lymphoma (pc-FCL), 1.7% and 3.0% subsequently developed extracutaneous involvement (median follow-up of 45 and 47 months respectively).Retrospective nature of this study.Imaging is effective in identifying the patients with systemic involvement in indolent BCLs presenting in the skin, however incidence is low. After negative initial staging, pc-MZL patients may be followed clinically without routine imaging.

    View details for PubMedID 30703460

  • Larry Emanuel Kun, March 10, 1946-May 27, 2018 OBITUARY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS FitzGerald, T. J., Donaldson, S. S., Wharam, M., Laurie, F., Bishop-Jodoin, M., Moni, J., Tarbell, N., Shulkin, B., McCarville, E., Merchant, T., Krasin, M., Wolden, S., Halperin, E., Constine, L. S., Haas-Kogan, D., Marcus, K., Freeman, C., Wilson, J., Hoppe, R., Cox, J., Terezakis, S., Million, L., Smith, M. A., Mendenhall, N. P., Marcus, R. B., Cherlow, J., Kalapurakal, J., Breneman, J., Yock, T., MacDonald, S., Laack, N., Donahue, B., Indelicato, D., Michalski, J., Perkins, S., Kachnic, L., Choy, H., Braunstein, S., Esiashvilli, N., Roberts, K. B. 2019; 103 (1): 8–14
  • Tomayto, tomahto: prescription dose and mean heart dose in evaluating the cardiac impact of involved-field radiation therapy for Hodgkin lymphoma survivors. Acta oncologica (Stockholm, Sweden) Bates, J. E., Flampouri, S., Hoppe, R. T., Li, Z., Mendenhall, N. P., Hoppe, B. S. 2019; 58 (12): 1783–85

    View details for DOI 10.1080/0284186X.2019.1657943

    View details for PubMedID 31742489

  • Prognostic factors and patterns of failure in advanced stage Hodgkin lymphoma treated with combined modality therapy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Moding, E. J., Advani, R., Rosenberg, S. A., Hoppe, R. T. 2018; 129 (3): 507–12

    Abstract

    BACKGROUND AND PURPOSE: The role of irradiation to non-bulky and bulky sites of disease in advanced stage Hodgkin lymphoma is controversial. We aimed to review the long-term outcomes of patients treated with combined modality therapy to clarify the role of consolidative radiotherapy.MATERIALS AND METHODS: Patients with stage III or IV Hodgkin lymphoma treated with Stanford V chemotherapy and consolidative radiotherapy to initial sites of disease ≥5 cm were analyzed retrospectively to determine patient outcomes, patterns of failure, and factors associated with treatment failure.RESULTS: A total of 170 patients were analyzed. Overall survival was 91.2%, freedom from progression was 80.6%, and progression-free survival was 78.9% at 10 years. 5 patients (2.9%) had refractory disease and 27 patients (15.9%) relapsed after treatment. Only an International Prognostic Score (IPS) greater than 2 predicted disease progression. 19 out of 27 relapses occurred exclusively outside of the radiation treatment field, and 17 out of 27 relapses occurred exclusively at original sites of disease. However, only 11 of 170 patients (6.5%) relapsed exclusively at original, non-bulky sites of disease not treated with radiation therapy. The cumulative incidence of local failure at 10 years was 4.6% for unirradiated sites and 2.6% for irradiated sites.CONCLUSION: Patients with advanced stage Hodgkin lymphoma treated with combined modality therapy including consolidative radiotherapy to bulky disease sites had excellent long-term outcomes. Given the low frequency of isolated failures at initial sites, our results suggest that selective radiation therapy to sites at high risk of relapse may be feasible.

    View details for PubMedID 30539763

  • Prognostic factors and patterns of failure in advanced stage Hodgkin lymphoma treated with combined modality therapy RADIOTHERAPY AND ONCOLOGY Moding, E. J., Advani, R., Rosenberg, S. A., Hoppe, R. T. 2018; 129 (3): 507–12
  • Nonmyeloablative Allogeneic Transplantation Using TLI-ATG Conditioning for Lymphoid and Myeloid Malignancies: Mature Follow-up from a Large, Single Institution Cohort Spinner, M. A., Kennedy, V. E., Tamaresis, J. S., Lavori, P. W., Elder, L. V., Arai, S., Johnston, L. J., Meyer, E. H., Miklos, D. B., Muffly, L. S., Negrin, R. S., Rezvani, A. R., Shizuru, J. A., Weng, W., Hoppe, R. T., Strober, S., Lowsky, R. AMER SOC HEMATOLOGY. 2018
  • No Utility of Routine Laboratory Testing during Surveillance in Detecting Relapse in Patients with Classic Hodgkin Lymphoma in First Remission Lynch, R. C., Sundaram, V., Desai, M., Henry, S., Wood, D., Daadi, S., Corbelli, K. S., Rosenberg, S., Hoppe, R. T., Advani, R. AMER SOC HEMATOLOGY. 2018
  • Definitive radiotherapy for localized follicular lymphoma staged by 18F-FDG PET-CT: a collaborative study by ILROG. Blood Brady, J. L., Binkley, M. S., Hajj, C., Chelius, M., Chau, K., Balogh, A., Levis, M., Filippi, A. R., Jones, M., Mac Manus, M., Wirth, A., Oguchi, M., Krog Vistisen, A., Andraos, T. Y., Ng, A. K., Aleman, B. M., Choi, S. H., Kirova, Y., Hardy, S., Reinartz, G., Eich, H. T., Bratman, S. V., Constine, L. S., Suh, C., Dabaja, B., El-Galaly, T. C., Hodgson, D. C., Ricardi, U., Yahalom, J., Hoppe, R. T., Mikhaeel, N. G. 2018

    Abstract

    Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40-50%. As 18F-FDG PET-CT upstages 10-60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study. Inclusion criteria were: RT alone for untreated stage I-II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow up ≥3 months. Endpoints were freedom from progression (FFP), local control, and overall survival (OS). FFP and OS were estimated with Kaplan-Meier, and uni- and multivariable analyses of prognostic factors performed with Cox Regression. 512 patients treated from 2000-2017 at 16 centres were eligible for analysis. Median age was 58 years (range 20-90). 410 patients (80.1%) had stage I disease. Median RT dose was 30 Gy (24-52). Median follow up was 52 months (3.2-174.6). 5y-FFP and OS were 68.9% and 95.7%. For stage I, 5y-FFP was 74.1%, vs 49.1% for stage II (p<0.0001). 8 patients relapsed infield (1.6%).4 had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (HR=2.11, 95%CI=1.44-3.10) and BCL2 expression (HR =1.62, 95%CI 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.

    View details for PubMedID 30446493

  • In Situ Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma CANCER DISCOVERY Frank, M. J., Reagan, P. M., Bartlett, N. L., Gordon, L., Friedberg, J. W., Czerwinski, D. K., Long, S. R., Hoppe, R. T., Janssen, R., Candia, A. F., Coffman, R. L., Levy, R. 2018; 8 (10): 1258–69
  • In Situ Vaccination with a TLR 9 Agonist and Local Low Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma. Cancer discovery Frank, M. J., Reagan, P. M., Bartlett, N. L., Gordon, L. I., Friedberg, J. W., Czerwinski, D. K., Long, S. R., Hoppe, R. T., Janssen, R. S., Candia, A. F., Coffman, R. L., Levy, R. 2018

    Abstract

    This multicenter phase 1/2 clinical trial evaluated intratumoral SD-101, a TLR9 agonist, and low-dose radiation in patients with untreated indolent lymphoma. 29 enrolled patients received 4 Gy of radiation followed by five weekly intratumoral injections of SD-101 at a single tumor site. No treatment-related grade 4 or serious adverse events occurred. Nearly all patients had tumor reduction at their treated site. More importantly, 24 patients had tumor reduction at their non-treated sites with 5 patients achieving a partial response and one achieving a complete response. Treatment-related increases of CD8+ and CD4+ effector T-cells and decreases of T Follicular Helper and T regulatory cells (Tregs) were observed in the tumor microenvironment. Low pre-treatment levels of CD4+ Tregs, proliferating CD8+ T-cells, and GranzymeB+ CD8+ T-cells were associated with favorable outcomes. Intratumoral SD-101 in combination with low-dose radiation is well tolerated and results in regression of both treated and untreated sites of disease.

    View details for PubMedID 30154192

  • Relationship Between Mixed Chimerism and Acceptance of HLA-matched and -Mismatched Kidney Transplants after Withdrawal of Immunosuppressive Drugs Busque, S., Scandling, J., Lowsky, R., Shizuru, J., Jensen, K., Shori, A., Hoppe, R., Engleman, E., Meyer, E., Strober, S. LIPPINCOTT WILLIAMS & WILKINS. 2018: S393
  • The Role of Radiation Therapy in Patients With Relapsed or Refractory Hodgkin Lymphoma: Guidelines From the International Lymphoma Radiation Oncology Group INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Constine, L. S., Yahalom, J., Ng, A. K., Hodgson, D. C., Wirth, A., Milgrom, S. A., Mikhaeel, N., Eich, H., Illidge, T., Ricardi, U., Dieckmann, K., Moskowitz, C. H., Advani, R., Mauch, P. M., Specht, L., Hoppe, R. T. 2018; 100 (5): 1100–1118

    Abstract

    Relapsed and refractory Hodgkin lymphoma (HL) challenges clinicians to devise treatment strategies that are effective and safe. This problem is particularly prominent in an era when de-escalation trials are designed to minimize therapeutic toxicities in both early- and advanced-stage disease. Radiation therapy is the single most effective treatment modality for HL, and its integration into salvage regimens, or its independent use in select patients, must be understood to maximize our success in treating these patients. The complexity of treating relapsed or refractory HL derives from the spectrum of primary treatment approaches currently in use that creates heterogeneity in both treatment exposure and the potential toxicities of salvage therapy. Patients can have relapsed or refractory disease after limited or aggressive primary therapy (with or without radiation therapy), at early or delayed time points, with limited or extensive disease volumes, and with varying degrees of residual morbidity from primary therapy. Their response to salvage systemic therapy can be partial or complete, and the use of consolidative stem cell transplantation is variably applied. New biologics and immunotherapeutic approaches have broadened but also complicated salvage treatment approaches. Through all of this, radiation therapy remains an integral component of treatment for many patients, but it must be used effectively and judiciously. The purpose of this review is to describe the different treatment scenarios and provide guidance for radiation dose, volume, and timing in patients with relapsed or refractory HL.

    View details for PubMedID 29722655

  • NCCN Guidelines (R) Insights Hodgkin Lymphoma, Version 1.2018 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Hoppe, R. T., Advani, R. H., Ai, W. Z., Ambinder, R. F., Aoun, P., Armand, P., Bello, C. M., Benitez, C. M., Bierman, P. J., Chen, R., Dabaja, B., Dean, R., Forero, A., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Hochberg, E. P., Huang, J., Johnston, P. B., Kaminski, M. S., Kenkre, V. P., Khan, N., Maddocks, K., Maloney, D. G., Metzger, M., Moore, J. O., Morgan, D., Moskowitz, C. H., Mulroney, C., Rabinovitch, R., Seropian, S., Tao, R., Winter, J. N., Yahalom, J., Burns, J. L., Ogba, N. 2018; 16 (3): 245–54

    Abstract

    The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN Guidelines Panel meets at least annually to review comments from reviewers within the NCCN Member Institutions, examine relevant data, and reevaluate and update the recommendations. These NCCN Guidelines Insights summarize recent updates centered on treatment considerations for relapsed/refractory classic HL.

    View details for DOI 10.6004/jnccn.2018.0013

    View details for Web of Science ID 000427032100007

    View details for PubMedID 29523663

  • NCCN Guidelines (R) Insights T-Cell Lymphomas, Version 2.2018 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Horwitz, S. M., Ansell, S. M., Ai, W. Z., Barnes, J., Barta, S. K., Choi, M., Clemens, M. W., Dogan, A., Greer, J. P., Halwani, A., Haverkos, B. M., Hoppe, R. T., Jacobsen, E., Jagadeesh, D., Kim, Y. H., Lunning, M. A., Mehta, A., Mehta-Shah, N., Oki, Y., Olsen, E. A., Pro, B., Rajguru, S. A., Shanbhag, S., Shustov, A., Sokol, L., Torka, P., Wilcox, R., William, B., Zain, J., Dwyer, M. A., Sundar, H. 2018; 16 (2): 123–35

    Abstract

    Natural killer (NK)/T-cell lymphomas are a rare and distinct subtype of non-Hodgkin's lymphomas. NK/T-cell lymphomas are predominantly extranodal and most of these are nasal type, often localized to the upper aerodigestive tract. Because extranodal NK/T-cell lymphomas (ENKL) are rare malignancies, randomized trials comparing different regimens have not been conducted to date and standard therapy has not yet been established for these patients. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with ENKL as outlined in the NCCN Guidelines for T-Cell Lymphomas.

    View details for DOI 10.6004/jnccn.2018.0007

    View details for Web of Science ID 000424512500005

    View details for PubMedID 29439173

  • Allogeneic transplantation using TLI-ATG conditioning for Hodgkin lymphoma after failure of autologous transplantation. Blood advances Spinner, M. A., Advani, R. H., Hoppe, R. T., Lowsky, R., Muffly, L. S. 2018; 2 (13): 1547–50

    View details for PubMedID 29970391

  • Evidence-based Review on the Use of Proton Therapy in Lymphoma From the Particle Therapy Cooperative Group (PTCOG) Lymphoma Subcommittee INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Tseng, Y. D., Cutter, D. J., Plastaras, J. P., Parikh, R. R., Cahlon, O., Chuong, M. D., Dedeckova, K., Khan, M. K., Lin, S., McGee, L. A., Shen, E., Terezakis, S. A., Badiyan, S. N., Kirova, Y. M., Hoppe, R. T., Mendenhall, N. P., Pankuch, M., Flampouri, S., Ricardi, U., Hoppe, B. S. 2017; 99 (4): 825–42

    View details for PubMedID 28943076

  • Post-treatment surveillance imaging in lymphoma SEMINARS IN ONCOLOGY Hiniker, S. M., Hoppe, R. T. 2017; 44 (5): 310–22

    Abstract

    Appropriate post-treatment management of patients with lymphoma has been controversial, with imaging frequently performed as post-treatment surveillance. The goal of post-treatment imaging is to identify relapse prior to clinical symptoms, when the burden of disease is lower and the possibility of effective salvage therapy and cure are greater. However, little data exist to support the performance of surveillance imaging after completion of treatment, with the vast majority of studies suggesting there is no clinical benefit to surveillance imaging in asymptomatic patients. Ongoing efforts seek to identify a subset of patients with a higher risk of relapse that might benefit from surveillance imaging, though financial and other costs associated with imaging are non-negligible and must be considered. Here we summarize the current data regarding post-treatment surveillance imaging in lymphoma.

    View details for PubMedID 29580433

  • Hodgkin Lymphoma Version 1.2017 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Hoppe, R. T., Advani, R. H., Ai, W. Z., Ambinder, R. F., Aoun, P., Bello, C. M., Benitez, C. M., Bernat, K., Bierman, P. J., Blum, K. A., Chen, R., Dabaja, B., Forero, A., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Hochberg, E. P., Huang, J., Johnston, P. B., Kaminski, M. S., Kenkre, V. P., Khan, N., Maloney, D. G., Mauch, P. M., Metzger, M., Moore, J. O., Morgan, D., Moskowitz, C. H., Mulroney, C., Poppe, M., Rabinovitch, R., Seropian, S., Smith, M., Winter, J. N., Yahalom, J., Burns, J., Ogba, N., Sundar, H. 2017; 15 (5): 608-638

    Abstract

    This portion of the NCCN Guidelines for Hodgkin lymphoma (HL) focuses on the management of classical HL. Current management of classical HL involves initial treatment with chemotherapy or combined modality therapy followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale). The introduction of less toxic and more effective regimens has significantly advanced HL cure rates. However, long-term follow-up after completion of treatment is essential to determine potential long-term effects.

    View details for Web of Science ID 000401120200011

  • Hodgkin Lymphoma: Current Status and Clinical Trial Recommendations JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Diefenbach, C. S., Connors, J. M., Friedberg, J. W., Leonard, J. P., Kahl, B. S., Little, R. F., Baizer, L., Evens, A. M., Hoppe, R. T., Kelly, K. M., Persky, D. O., Younes, A., Kostakaglu, L., Bartlett, N. L. 2017; 109 (4)

    Abstract

    The National Clinical Trials Network lymphoid malignancies Clinical Trials Planning Meeting (CTPM) occurred in November of 2014. The scope of the CTPM was to prioritize across the lymphoid tumors clinically significant questions and to foster strategies leading to biologically informed and potentially practice changing clinical trials. This review from the Hodgkin lymphoma (HL) subcommittee of the CTPM discusses the ongoing clinical challenges in HL, outlines the current standard of care for HL patients from early to advanced stage, and surveys the current science with respect to biomarkers and the landscape of ongoing clinical trials. Finally, we suggest areas of unmet need in HL and elucidate promising therapeutic strategies to guide future HL clinical trials planning across the NCTN.

    View details for PubMedID 28040700

  • NCCN Guidelines (R) Insights Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia, Version 1.2017 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Wierda, W. G., Zelenetz, A. D., Gordon, L. I., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Byrd, J. C., Caimi, P., Fayad, L. E., Fisher, R. I., Glenn, M. J., Habermann, T. M., Harris, N. L., Hernandez-Ilizaliturri, F., Hoppe, R. T., Horwitz, S. M., Kaminski, M. S., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Martin, M. G., Nademanee, A., Porcu, P., Press, O., Rabinovitch, R., Reddy, N., Reid, E., Roberts, K., Saad, A. A., Snyder, E. D., Sokol, L., Swinnen, L. J., Vose, J. M., Yahalom, J., Dwyer, M. A., Sundar, H. 2017; 15 (3): 293-311

    Abstract

    Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are different manifestations of the same disease and managed in much the same way. The advent of novel CD20 monoclonal antibodies led to the development of effective chemoimmunotherapy regimens. More recently, small molecule inhibitors targeting kinases involved in a number of critical signaling pathways and a small molecule inhibitor of the BCL-2 family of proteins have demonstrated activity for the treatment of patients with CLL/SLL. These NCCN Guidelines Insights highlight important updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for CLL/SLL for the treatment of patients with newly diagnosed or relapsed/refractory CLL/SLL.

    View details for Web of Science ID 000395889300004

  • Remarkable Advances in the Management of Mycosis Fungoides and the Sezary Syndrome ONCOLOGY RESEARCH AND TREATMENT Hoppe, R. T. 2017; 40 (5): 242–43

    View details for DOI 10.1159/000475528

    View details for Web of Science ID 000400924600001

    View details for PubMedID 28423383

  • Localized skin-limited blastic plasmacytoid dendritic cell neoplasm: A subset with possible durable remission without transplantation. JAAD case reports Amitay-Laish, I., Sundram, U., Hoppe, R. T., Hodak, E., Medeiros, B. C., Kim, Y. H. 2017; 3 (4): 310–15

    View details for DOI 10.1016/j.jdcr.2017.03.015

    View details for PubMedID 28752118

    View details for PubMedCentralID PMC5517837

  • A Single-Arm PHASE 2A Study of NM-IL-12 (rHu-IL12) in Patients with Mycosis Fungoides-Type CTCL (MF) Undergoing Low-Dose TOTAL Skin Electron BEAM Therapy (LD-TSEBT) Kim, Y. H., Hoppe, R. T., Rook, A. H., Maity, A., Geskin, L. J., Horowitz, D. P., Finnegan, G., Khodadoust, M., Weng, W., Lares, A., Hong, E., Buchanan, M., Ma, V., Kha, H., Lawrence, C. E., Vainstein, V., Basile, L. A. AMER SOC HEMATOLOGY. 2016
  • Classical Hodgkin Lymphoma with Reduced ß2M/MHC Class I Expression Is Associated with Inferior Outcome Independent of 9p24.1 Status. Cancer immunology research Roemer, M. G., Advani, R. H., Redd, R. A., Pinkus, G. S., Natkunam, Y., Ligon, A. H., Connelly, C. F., Pak, C. J., Carey, C. D., Daadi, S. E., Chapuy, B., De Jong, D., Hoppe, R. T., Neuberg, D. S., Shipp, M. A., Rodig, S. J. 2016; 4 (11): 910-916

    Abstract

    In classical Hodgkin lymphoma (cHL), malignant Hodgkin Reed-Sternberg (HRS) cells evade antitumor immunity by multiple mechanisms, including perturbed antigen presentation and enhanced PD-1 signaling. HRS cell expression of the PD-1 ligands is attributable, in part, to copy number alterations of 9p24.1/CD274(PD-L1)/PDCD1LG2(PD-L2) Amplification of PD-L1/PD-L2 is associated with advanced clinical stage and inferior progression-free survival (PFS) following first-line (induction) therapy. The relationships between altered expression of β2-microglobulin (β2M), MHC class I, and MHC class II by HRS cells, PD-L1/PD-L2 amplification, and clinical outcome in cHL are poorly defined. We assessed these variables in diagnostic biopsy specimens from 108 patients with cHL who received uniform treatment and had long-term follow-up and found decreased/absent expression of β2M/MHC class I in 79% (85/108) and decreased/absent expression of MHC class II in 67% (72/108) of cases. Patients with decreased/absent β2M/MHC class I had shorter PFS, independent of PD-L1/PD-L2 amplification and advanced stage. Decreased or absent MHC class II was unrelated to outcome. These results suggest that MHC class I-mediated antigen presentation by HRS cells is an important component of the biological response to standard chemo/radiotherapy. The paucity of β2M/MHC class I expression on HRS cells also prompts speculation regarding alternative mechanisms of action of PD-1 blockade in cHL. Cancer Immunol Res; 4(11); 910-6. ©2016 AACR.

    View details for PubMedID 27737878

  • 2 Gy?×?2 for palliative treatment of mantle cell lymphoma. Leukemia & lymphoma White, E. C., Advani, R., Hoppe, R. T. 2016; 57 (9): 2219-2221

    View details for DOI 10.3109/10428194.2015.1131274

    View details for PubMedID 26763352

  • Non-Hodgkin's Lymphomas, Version 3.2016 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Horwitz, S. M., Zelenetz, A. D., Gordon, L. I., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Byrd, J. C., Fayad, L. E., Fisher, R. I., Glenn, M. J., Habermann, T. M., Harris, N. L., Hernandez-Ilizaliturri, F., Hoppe, R. T., Kaminski, M. S., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Lunning, M., Nademanee, A., Press, O., Rabinovitch, R., Reddy, N., Reid, E., Roberts, K., Saad, A. A., Sokol, L., Swinnen, L. J., Vose, J. M., Yahalom, J., Zafar, N., Dwyer, M., Sundar, H., Porcu, P. 2016; 14 (9): 1067-1079

    Abstract

    Peripheral T-cell lymphomas (PTCLs) represent a relatively uncommon heterogeneous group of non-Hodgkin's lymphomas (NHLs) with an aggressive clinical course and poor prognosis. Anthracycline-based multiagent chemotherapy with or without radiation therapy followed by first-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is the standard approach to most of the patients with newly diagnosed PTCL. Relapsed or refractory disease is managed with second-line systemic therapy followed by HDT/ASCR or allogeneic stem cell transplant, based on the patient's eligibility for transplant. In recent years, several newer agents have shown significant activity in patients with relapsed or refractory disease across all 4 subtypes of PTCL. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for NHL, specific to the management of patients with relapsed or refractory PTCL.

    View details for Web of Science ID 000382903900004

  • NCCN Guidelines Insights: Non-Hodgkin's Lymphomas, Version 3.2016. Journal of the National Comprehensive Cancer Network Horwitz, S. M., Zelenetz, A. D., Gordon, L. I., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Byrd, J. C., Fayad, L. E., Fisher, R. I., Glenn, M. J., Habermann, T. M., Lee Harris, N., Hernandez-Ilizaliturri, F., Hoppe, R. T., Kaminski, M. S., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Lunning, M., Nademanee, A., Press, O., Rabinovitch, R., Reddy, N., Reid, E., Roberts, K., Saad, A. A., Sokol, L., Swinnen, L. J., Vose, J. M., Yahalom, J., Zafar, N., Dwyer, M., Sundar, H., Porcu, P. 2016; 14 (9): 1067-1079

    Abstract

    Peripheral T-cell lymphomas (PTCLs) represent a relatively uncommon heterogeneous group of non-Hodgkin's lymphomas (NHLs) with an aggressive clinical course and poor prognosis. Anthracycline-based multiagent chemotherapy with or without radiation therapy followed by first-line consolidation with high-dose therapy followed by autologous stem cell rescue (HDT/ASCR) is the standard approach to most of the patients with newly diagnosed PTCL. Relapsed or refractory disease is managed with second-line systemic therapy followed by HDT/ASCR or allogeneic stem cell transplant, based on the patient's eligibility for transplant. In recent years, several newer agents have shown significant activity in patients with relapsed or refractory disease across all 4 subtypes of PTCL. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for NHL, specific to the management of patients with relapsed or refractory PTCL.

    View details for PubMedID 27587620

  • PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome. Journal of clinical oncology Roemer, M. G., Advani, R. H., Ligon, A. H., Natkunam, Y., Redd, R. A., Homer, H., Connelly, C. F., Sun, H. H., Daadi, S. E., Freeman, G. J., Armand, P., Chapuy, B., De Jong, D., Hoppe, R. T., Neuberg, D. S., Rodig, S. J., Shipp, M. A. 2016; 34 (23): 2690-2697

    Abstract

    Classical Hodgkin lymphomas (cHLs) include small numbers of malignant Reed-Sternberg cells within an extensive but ineffective inflammatory/immune cell infiltrate. In cHL, chromosome 9p24.1/PD-L1/PD-L2 alterations increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and their further induction through Janus kinase 2-signal transducers and activators of transcription signaling. The unique composition of cHL limits its analysis with high-throughput genomic assays. Therefore, the precise incidence, nature, and prognostic significance of PD-L1/PD-L2 alterations in cHL remain undefined.We used a fluorescent in situ hybridization assay to evaluate CD274/PD-L1 and PDCD1LG2/PD-L2 alterations in 108 biopsy specimens from patients with newly diagnosed cHL who were treated with the Stanford V regimen and had long-term follow-up. In each case, the frequency and magnitude of 9p24.1 alterations-polysomy, copy gain, and amplification-were determined, and the expression of PD-L1 and PD-L2 was evaluated by immunohistochemistry. We also assessed the association of 9p24.1 alterations with clinical parameters, which included stage (early stage I/II favorable risk, early stage unfavorable risk, advanced stage [AS] III/IV) and progression-free survival (PFS).Ninety-seven percent of all evaluated cHLs had concordant alterations of the PD-L1 and PD-L2 loci (polysomy, 5% [five of 108]; copy gain, 56% [61 of 108]; amplification, 36% [39 of 108]). There was an association between PD-L1 protein expression and relative genetic alterations in this series. PFS was significantly shorter for patients with 9p24.1 amplification, and the incidence of 9p24.1 amplification was increased in patients with AS cHL.PD-L1/PD-L2 alterations are a defining feature of cHL. Amplification of 9p24.1 is more common in patients with AS disease and associated with shorter PFS in this series. Further analyses of 9p24.1 alterations in patients treated with standard cHL induction regimens or checkpoint blockade are warranted.

    View details for DOI 10.1200/JCO.2016.66.4482

    View details for PubMedID 27069084

  • Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: An International Lymphoma Radiation Oncology Group Multi-institutional Experience. International journal of radiation oncology, biology, physics Million, L., Yi, E. J., Wu, F., von Eyben, R., Campbell, B. A., Dabaja, B., Tsang, R. W., Ng, A., Wilson, L. D., Ricardi, U., Kirova, Y., Hoppe, R. T. 2016; 95 (5): 1454-1459

    Abstract

    To collect response rates of primary cutaneous anaplastic large cell lymphoma, a rare cutaneous T-cell lymphoma, to radiation therapy (RT), and to determine potential prognostic factors predictive of outcome.The study was a retrospective analysis of patients with primary cutaneous anaplastic large cell lymphoma who received RT as primary therapy or after surgical excision. Data collected include initial stage of disease, RT modality (electron/photon), total dose, fractionation, response to treatment, and local recurrence. Radiation therapy was delivered at 8 participating International Lymphoma Radiation Oncology Group institutions worldwide.Fifty-six patients met the eligibility criteria, and 63 tumors were treated: head and neck (27%), trunk (14%), upper extremities (27%), and lower extremities (32%). Median tumor size was 2.25 cm (range, 0.6-12 cm). T classification included T1, 40 patients (71%); T2, 12 patients (21%); and T3, 4 patients (7%). The median radiation dose was 35 Gy (range, 6-45 Gy). Complete clinical response (CCR) was achieved in 60 of 63 tumors (95%) and partial response in 3 tumors (5%). After CCR, 1 tumor recurred locally (1.7%) after 36 Gy and 7 months after RT. This was the only patient to die of disease.Primary cutaneous anaplastic large cell lymphoma is a rare, indolent cutaneous lymphoma with a low death rate. This analysis, which was restricted to patients selected for treatment with radiation, indicates that achieving CCR was independent of radiation dose. Because there were too few failures (<2%) for statistical analysis on dose response, 30 Gy seems to be adequate for local control, and even lower doses may suffice.

    View details for DOI 10.1016/j.ijrobp.2016.03.023

    View details for PubMedID 27315663

  • Partial orbit irradiation achieves excellent outcomes for primary orbital lymphoma. Practical radiation oncology Binkley, M. S., Hiniker, S. M., Donaldson, S. S., Hoppe, R. T. 2016; 6 (4): 255-261

    Abstract

    Primary radiation therapy (RT) achieves excellent local control and overall survival when treating localized orbital lymphoma. However, evidence supporting irradiation of partial orbit volumes to spare nearby critical structures is lacking. We sought to investigate outcomes for patients with localized orbital lymphoma treated with partial orbit irradiation.We retrospectively reviewed patients with orbital lymphoma treated with RT at our institution who met our inclusion criteria: biopsy-confirmed, low-grade lymphoma, localized disease, partial orbit treatment volumes, and follow-up >3months. The Kaplan-Meier method was used to measure overall survival (OS), and the cumulative incidence function adjusted for the competing risk of death was used to measure local failure (LF), contralateral orbit recurrence (COR), and progression. Patient characteristics were compared with outcomes using Fisher exact test for dichotomous variables and Wilcoxon rank-sum test for continuous variables.Thirty-two patients meeting inclusion criteria were identified with median follow-up of 45.8months (range, 3.6-171.9). The majority had stage IEA disease; their sites included conjunctiva (n=20) and retrobulbar or lacrimal gland (n=12). Median partial orbit RT dose was 30.6Gy (range, 22.5-36). Five-year OS was 100%. Five-year cumulative incidence of LF, COR, and overall disease progression was 5.3%, 5.9%, and 21.4%, respectively. Five-year cumulative incidence of LF was 8.3% for conjunctival disease versus 0.0% for retrobulbar or lacrimal gland involvement (P=.15). No significant association was observed between the outcomes of LF, COR, or progression and pretreatment characteristics. Acute and late toxicity included grade 2 periorbital edema (n=3, 9.4%), dry eye (n=3, 9.4%), retinal vascular disorder (n=1, 3.1%), conjunctivitis (n=2, 6.3%), and grade 3 cataract (n=1, 3.1%).Use of partial orbit irradiation in treating low-grade, localized orbital lymphoma achieves excellent survival with low rates of LF, COR, or progression.

    View details for DOI 10.1016/j.prro.2015.11.013

    View details for PubMedID 26935235

  • How I treat mycosis fungoides and Sezary syndrome BLOOD Whittaker, S., Hoppe, R., Prince, H. M. 2016; 127 (25): 3142-3153

    Abstract

    Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma variant and is closely related to a rare leukemic variant, Sézary syndrome (SS). MF patients at risk of disease progression can now be identified and an international consortium has been established to address the prognostic relevance of specific biologic factors and define a prognostic index. There are a lack of randomized clinical trial data in MF/SS and evidence is based on a traditional "stage-based" approach; treatment of early-stage disease (IA-IIA) involves skin directed therapies which include topical corticosteroids, phototherapy (psoralen with UVA or UVB), topical chemotherapy, topical bexarotene, and radiotherapy including total skin electron beam therapy. Systemic approaches are used for refractory early-stage and advanced-stage disease (IIB-IV) and include bexarotene, interferon α, extracorporeal photopheresis, histone deacetylase inhibitors, and antibody therapies such as alemtuzumab, systemic chemotherapy, and allogeneic transplantation. However, despite the number of biologic agents available, the treatment of advanced-stage disease still represents an unmet medical need with short duration of responses. Encouragingly, randomized phase 3 trials are assessing novel agents, including brentuximab vedotin and the anti-CCR4 antibody, mogamulizumab. A broader understanding of the biology of MF/SS will hopefully identify more effective targeted therapies.

    View details for DOI 10.1182/blood-2015-12-611830

    View details for Web of Science ID 000378337700008

    View details for PubMedID 27151889

  • Re-Examining the Role of Radiation Therapy for Diffuse Large B-Cell Lymphoma in the Modern Era JOURNAL OF CLINICAL ONCOLOGY Ng, A. K., Dabaja, B., Hoppe, R. T., Illidge, T., Yahalom, J. 2016; 34 (13): 1443-+

    View details for PubMedID 26903576

  • Breast Imaging in Women Previously Irradiated for Hodgkin Lymphoma. American journal of clinical oncology Horst, K. C., Fero, K. E., Hancock, S. L., Advani, R. H., Ikeda, D. M., Daniel, B., Rosenberg, S. A., Donaldson, S. S., Hoppe, R. T. 2016; 39 (2): 114-119

    Abstract

    Women treated with mantle irradiation for Hodgkin lymphoma (HL) are at an increased risk of developing breast cancer (BC). Current guidelines recommend screening breast magnetic resonance imaging (MRI) as an adjunct to mammography (M) in these patients. There are limited data, however, as to the impact of breast MRI on cancer detection rates. The aim of the current study is to evaluate the use of breast MRI in survivors of HL treated and followed at a single institution.We retrospectively reviewed 980 female patients treated with mantle irradiation for HL between 1961 and 2008. Records were reviewed to determine age at radiotherapy treatment, radiotherapy dose, breast imaging (including M and breast MRI), biopsy results if applicable, and incidence of BC.A total of 118 patients had breast imaging performed at our institution. Median age at HL diagnosis was 28 years (range, 10 to 69 y). Median radiotherapy dose was 36 Gy (range, 20 to 45 Gy). Seventy-nine patients (67%) underwent M screening only, 1 (1%) breast MRI only, and 38 (32%) both M and breast MRI. Of these 38, 19 (50%) underwent 54 screening MRI studies (range per patient=1 to 8), 13 (34%) underwent preoperative MRI for workup of BC, and 6 (16%) initiated screening MRI of the contralateral breast only after diagnosed with BC. Fifty-nine biopsies were performed: 47 were prompted by suspicious M findings only, 10 by palpable findings on physical examination (PE), and 2 by suspicious breast MRI findings. Of the 47 biopsies prompted by M, 24 revealed malignant disease, whereas 23 proved to be benign. All 10 biopsies performed by palpation were malignant. Both biopsies prompted by MRI findings were benign. With M, there were 34 true-positive findings in 32 patients, 23 false-positive findings, and 1 false-negative finding. With screening MRI, there were 2 false-positive findings, 1 false-negative finding, and no true-positive findings.The role of screening breast MRI in women previously irradiated for HL is evolving. Further education of patients and physicians is important to increase awareness of more sensitive BC screening modalities in this high-risk population. Future studies are necessary to determine the appropriate integration of screening breast MRI into the ongoing follow-up of these women.

    View details for DOI 10.1097/COC.0000000000000025

    View details for PubMedID 24390271

  • A single-institution retrospective analysis of outcomes for stage I-II primary mediastinal large B-cell lymphoma treated with immunochemotherapy with or without radiotherapy LEUKEMIA & LYMPHOMA Binkley, M. S., Hiniker, S. M., Wu, S., Natkunam, Y., Mittra, E. S., Advani, R. H., Hoppe, R. T. 2016; 57 (3): 604-608

    Abstract

    As the optimal treatment for primary mediastinal large B-cell lymphoma (PMBCL) remains undefined, we evaluated outcomes of patients treated with standard and dose-intense rituximab-chemotherapy (R-CT) with and without radiotherapy (RT). We retrospectively identified 28 patients with stage I-II PMBCL in our lymphoma database, re-reviewed pathology slides and scored interim or post-chemotherapy PET/CTs using the Deauville scale. Fourteen patients received RT (36-45 Gy) preceded by either six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or 12 weeks of rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin (R-VACOP-B) with median follow-up of 94 months. Fourteen patients received 4-8 cycles of dose-adjusted etoposide, vincristine, doxorubicin, cyclophosphamide and rituximab (DA-EPOCH-R) with median follow-up of 38 months; one of these received RT (36 Gy) due to post-chemotherapy PET/CT Deauville score 4. Following R-CT and RT or DA-EPOCH-R, 5-year and 3-year FFP and OS were both 100%. Both R-CHOP/R-VACOP-B with RT and DA-EPOCH-R demonstrate excellent outcomes.

    View details for DOI 10.3109/10428194.2015.1067700

    View details for Web of Science ID 000372499800016

  • A single-institution retrospective analysis of outcomes for stage I-II primary mediastinal large B-cell lymphoma treated with immunochemotherapy with or without radiotherapy. Leukemia & lymphoma Binkley, M. S., Hiniker, S. M., Wu, S., Natkunam, Y., Mittra, E. S., Advani, R. H., Hoppe, R. T. 2016; 57 (3): 604-608

    Abstract

    As the optimal treatment for primary mediastinal large B-cell lymphoma (PMBCL) remains undefined, we evaluated outcomes of patients treated with standard and dose-intense rituximab-chemotherapy (R-CT) with and without radiotherapy (RT). We retrospectively identified 28 patients with stage I-II PMBCL in our lymphoma database, re-reviewed pathology slides and scored interim or post-chemotherapy PET/CTs using the Deauville scale. Fourteen patients received RT (36-45 Gy) preceded by either six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or 12 weeks of rituximab, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin (R-VACOP-B) with median follow-up of 94 months. Fourteen patients received 4-8 cycles of dose-adjusted etoposide, vincristine, doxorubicin, cyclophosphamide and rituximab (DA-EPOCH-R) with median follow-up of 38 months; one of these received RT (36 Gy) due to post-chemotherapy PET/CT Deauville score 4. Following R-CT and RT or DA-EPOCH-R, 5-year and 3-year FFP and OS were both 100%. Both R-CHOP/R-VACOP-B with RT and DA-EPOCH-R demonstrate excellent outcomes.

    View details for DOI 10.3109/10428194.2015.1067700

    View details for PubMedID 26159046

  • Diffuse Large B-Cell Lymphoma Version 1.2016 Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Zelenetz, A. D., Gordon, L. I., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Byrd, J. C., Fayad, L. E., Fisher, R. I., Glenn, M. J., Habermann, T. M., Harris, N. L., Hernandez-Ilizaliturri, F., Hoppe, R. T., Horwitz, S. M., Kaminski, M. S., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Lunning, M., Nademanee, A., Porcu, P., Press, O., Rabinovitch, R., Reddy, N., Reid, E., Roberts, K., Saad, A. A., Sokol, L., Swinnen, L. J., Vose, J. M., Yahalom, J., Zafar, N., Dwyer, M., Sundar, H. 2016; 14 (2): 196-231

    Abstract

    Diffuse large B-cell lymphomas (DLBCL) are now considered a heterogeneous group of distinct molecular subtypes (germinal center B-cell DLBCL, activated B-cell DLBCL, and primary mediastinal large B-cell lymphoma (PMBL) with varied natural history and response to therapy. In addition, a subset of patients with DLBCL have concurrent MYC and/or BCL2 gene rearrangements (double-hit lymphomas; DHL) and others have a dual expression of both MYC and BCL2 proteins (double-expressing DLBCL; DEL). The standard of care for the treatment of patients with PMBL, DHL, or DEL has not been established. Adequate immunophenotyping and molecular testing (in selected circumstances) are necessary for the accurate diagnosis of different subtypes of DLBCL. The NCCN Guidelines included in this issue, part of the NCCN Guidelines for non-Hodgkin's lymphomas, address the diagnosis and management of DLBCL and its subtypes.

    View details for Web of Science ID 000369634300011

  • Are Advanced Radiation Therapy Technologies Required for Treating Patients With Hodgkin Lymphoma? JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Hoppe, R. T. 2016; 14 (1): 2–3

    View details for DOI 10.6004/jnccn.2016.0002

    View details for Web of Science ID 000367629000003

    View details for PubMedID 26733550

  • PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome Roemer, M. M., Advani, R. H., Ligon, A. H., Natkunam, Y., Redd, R. A., Homer, H., Connelly, C., Sun, H. H., Daadi, S. E., Chapuy, B., de Jong, D., Hoppe, R. T., Neuberg, D. S., Rodig, S. J., Shipp, M. A. AMER SOC HEMATOLOGY. 2015
  • Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. Journal of clinical oncology Kim, Y. H., Tavallaee, M., Sundram, U., Salva, K. A., Wood, G. S., Li, S., Rozati, S., Nagpal, S., Krathen, M., Reddy, S., Hoppe, R. T., Nguyen-Lin, A., Weng, W., Armstrong, R., Pulitzer, M., Advani, R. H., Horwitz, S. M. 2015; 33 (32): 3750-3758

    Abstract

    In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored.In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety.Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event.Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin.

    View details for DOI 10.1200/JCO.2014.60.3969

    View details for PubMedID 26195720

  • Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model. Journal of clinical oncology Scarisbrick, J. J., Prince, H. M., Vermeer, M. H., Quaglino, P., Horwitz, S., Porcu, P., Stadler, R., Wood, G. S., Beylot-Barry, M., Pham-Ledard, A., Foss, F., Girardi, M., Bagot, M., Michel, L., Battistella, M., Guitart, J., Kuzel, T. M., Martinez-Escala, M. E., Estrach, T., Papadavid, E., Antoniou, C., Rigopoulos, D., Nikolaou, V., Sugaya, M., Miyagaki, T., Gniadecki, R., Sanches, J. A., Cury-Martins, J., Miyashiro, D., Servitje, O., Muniesa, C., Berti, E., Onida, F., Corti, L., Hodak, E., Amitay-Laish, I., Ortiz-Romero, P. L., Rodríguez-Peralto, J. L., Knobler, R., Porkert, S., Bauer, W., Pimpinelli, N., Grandi, V., Cowan, R., Rook, A., Kim, E., Pileri, A., Patrizi, A., Pujol, R. M., Wong, H., Tyler, K., Stranzenbach, R., Querfeld, C., Fava, P., Maule, M., Willemze, R., Evison, F., Morris, S., Twigger, R., Talpur, R., Kim, J., Ognibene, G., Li, S., Tavallaee, M., Hoppe, R. T., Duvic, M., Whittaker, S. J., Kim, Y. H. 2015; 33 (32): 3766-3773

    Abstract

    Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers.Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS).Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%).To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value, which, used together in a prognostic index, may be useful to stratify advanced-stage patients.

    View details for DOI 10.1200/JCO.2015.61.7142

    View details for PubMedID 26438120

  • Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project. Journal of clinical oncology Kim, Y. H., Tavallaee, M., Sundram, U., Salva, K. A., Wood, G. S., Li, S., Rozati, S., Nagpal, S., Krathen, M., Reddy, S., Hoppe, R. T., Nguyen-Lin, A., Weng, W., Armstrong, R., Pulitzer, M., Advani, R. H., Horwitz, S. M. 2015; 33 (32): 3750-3758

    View details for DOI 10.1200/JCO.2014.60.3969

    View details for PubMedID 26195720

  • Evaluation of the International Prognostic Score (IPS-7) and a Simpler Prognostic Score (IPS-3) for advanced Hodgkin lymphoma in the modern era BRITISH JOURNAL OF HAEMATOLOGY Diefenbach, C. S., Li, H., Hong, F., Gordon, L. I., Fisher, R. I., Bartlett, N. L., Crump, M., Gascoyne, R. D., Wagner, H., Stiff, P. J., Cheson, B. D., Stewart, D. A., Kahl, B. S., Friedberg, J. W., Blum, K. A., Habermann, T. M., Tuscano, J. M., Hoppe, R. T., Horning, S. J., Advani, R. H. 2015; 171 (4): 530-538

    Abstract

    The International Prognostic Score (IPS-7) is the most commonly used risk stratification tool for advanced Hodgkin lymphoma (HL), however recent studies suggest the IPS-7 is less discriminating due to improved outcomes with contemporary therapy. We evaluated the seven variables for IPS-7 recorded at study entry for 854 patients enrolled on Eastern Cooperative Oncology Group 2496 trial. Univariate and multivariate Cox models were used to assess their prognostic ability for freedom from progression (FFP) and overall survival (OS). The IPS-7 remained prognostic however its prognostic range has narrowed. On multivariate analysis, two factors (age, stage) remained significant for FFP and three factors (age, stage, haemoglobin level) for OS. An alternative prognostic index, the IPS-3, was constructed using age, stage and haemoglobin level, which provided four distinct risk groups [FFP (P = 0·0001) and OS (P < 0·0001)]. IPS-3 outperformed the IPS-7 on risk prediction for both FFP and OS by model fit and discrimination criteria. Using reclassification calibration, 18% of IPS-7 low risk patients were re-classified as intermediate risk and 13% of IPS-7 intermediate risk patients as low risk. For patients with advanced HL, the IPS-3 may provide a simpler and more accurate framework for risk assessment in the modern era. Validation of these findings in other large data sets is planned.

    View details for DOI 10.1111/bjh.13634

    View details for PubMedID 26343802

  • Hodgkin Lymphoma: the Changing Role of Radiation Therapy in Early-Stage Disease-the Role of Functional Imaging. Current treatment options in oncology Iberri, D. J., Hoppe, R. T., Advani, R. H. 2015; 16 (9): 360-?

    View details for DOI 10.1007/s11864-015-0360-6

    View details for PubMedID 26187795

  • Hodgkin Lymphoma: the Changing Role of Radiation Therapy in Early-Stage Disease—the Role of Functional Imaging. Current treatment options in oncology Iberri, D. J., Hoppe, R. T., Advani, R. H. 2015; 16 (9): 45-?

    Abstract

    Early-stage classical Hodgkin lymphoma (CHL) is a highly curable malignancy. Historically, extended-field radiotherapy (EFRT) alone showed excellent cure rates, but the risk of radiotherapy (RT)-associated toxicities led to combined modality therapy (CMT) replacing RT alone. RT has subsequently evolved further with significant reductions of dose and field size, and is currently restricted to involved sites only (ISRT). Contemporary CMT yields cure rates in excess of 85 %, and most studies do not have adequate follow-up required to evaluate the risk reduction in late effects. In an effort to avoid RT altogether, response-adapted treatment approaches utilizing results of interim [(18)F]fluorodeoxyglucose (FDG) positron emission tomography with fused computed tomography (PET/CT) imaging have been studied. Results from two studies in favorable-risk (UK RAPID and EORTC H10F) and one in unfavorable-risk patients (EORTC H10U) suggest that omission of RT in patients with a negative interim PET/CT response (Deauville score ≤2) yields slightly inferior progression-free survival (PFS) compared to conventional CMT, but with no difference in overall survival (OS) albeit with short-term follow-up. In order to extrapolate results to daily practice, it is critical to understand the selection of patients entered on trials since definitions of favorable and unfavorable disease vary between study groups. Currently, CMT continues to be the standard of care for the vast majority of patients with early-stage CHL and RT is an integral part of therapy in patients with bulky disease. However, for selected patients with favorable characteristics, emerging data suggest that a chemotherapy-alone approach is reasonable.

    View details for DOI 10.1007/s11864-015-0360-6

    View details for PubMedID 26187795

  • Biological characterization of stage I follicular lymphoma according to extranodal or nodal primary origin and t(14;18) status using high-resolution array-based comparative genomic hybridization AMERICAN JOURNAL OF HEMATOLOGY Weinberg, O. K., Ma, L., Hoppe, R. T., Arber, D. A. 2015; 90 (8): E151

    View details for PubMedID 25963736

  • Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial. Journal of clinical oncology Advani, R. H., Hong, F., Fisher, R. I., Bartlett, N. L., Robinson, K. S., Gascoyne, R. D., Wagner, H., Stiff, P. J., Cheson, B. D., Stewart, D. A., Gordon, L. I., Kahl, B. S., Friedberg, J. W., Blum, K. A., Habermann, T. M., Tuscano, J. M., Hoppe, R. T., Horning, S. J. 2015; 33 (17): 1936-1942

    Abstract

    The phase III North American Intergroup E2496 Trial (Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma) compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V). We report results of a planned subgroup analysis in patients with stage I or II bulky mediastinal Hodgkin lymphoma (HL).Patients were randomly assigned to six to eight cycles of ABVD every 28 days or Stanford V once per week for 12 weeks. Two to 3 weeks after completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT) to the mediastinum, hila, and supraclavicular regions. Patients on the Stanford V arm received IFRT to additional sites ≥ 5 cm at diagnosis. Primary end points were failure-free survival (FFS) and overall survival (OS).Of 794 eligible patients, 264 had stage I or II bulky disease, 135 received ABVD, and 129 received Stanford V. Patient characteristics were matched. The overall response rate was 83% with ABVD and 88% with Stanford V. At a median follow-up of 6.5 years, the study excluded a difference of more than 21% in 5-year FFS and more than 16% in 5-year OS between ABVD and Stanford V (5-year FFS: 85% v 79%; HR, 0.68; 95% CI, 0.37 to 1.25; P = .22; 5-year OS: 96% v 92%; HR, 0.49; 95% CI, 0.16 to 1.47; P = .19). In-field relapses occurred in < 10% of the patients in each arm.For patients with stage I or II bulky mediastinal HL, no substantial statistically significant differences were detected between the two regimens, although power was limited. To the best of our knowledge, this is the first prospective trial reporting outcomes specific to this subgroup, and it sets a benchmark for comparison of ongoing and future studies.

    View details for DOI 10.1200/JCO.2014.57.8138

    View details for PubMedID 25897153

  • Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial JOURNAL OF CLINICAL ONCOLOGY Advani, R. H., Hong, F., Fisher, R. I., Bartlett, N. L., Robinson, K. S., Gascoyne, R. D., Wagner, H., Stiff, P. J., Cheson, B. D., Stewart, D. A., Gordon, L. I., Kahl, B. S., Friedberg, J. W., Blum, K. A., Habermann, T. M., Tuscano, J. M., Hoppe, R. T., Horning, S. J. 2015; 33 (17): 1936-U111

    Abstract

    The phase III North American Intergroup E2496 Trial (Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma) compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V). We report results of a planned subgroup analysis in patients with stage I or II bulky mediastinal Hodgkin lymphoma (HL).Patients were randomly assigned to six to eight cycles of ABVD every 28 days or Stanford V once per week for 12 weeks. Two to 3 weeks after completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT) to the mediastinum, hila, and supraclavicular regions. Patients on the Stanford V arm received IFRT to additional sites ≥ 5 cm at diagnosis. Primary end points were failure-free survival (FFS) and overall survival (OS).Of 794 eligible patients, 264 had stage I or II bulky disease, 135 received ABVD, and 129 received Stanford V. Patient characteristics were matched. The overall response rate was 83% with ABVD and 88% with Stanford V. At a median follow-up of 6.5 years, the study excluded a difference of more than 21% in 5-year FFS and more than 16% in 5-year OS between ABVD and Stanford V (5-year FFS: 85% v 79%; HR, 0.68; 95% CI, 0.37 to 1.25; P = .22; 5-year OS: 96% v 92%; HR, 0.49; 95% CI, 0.16 to 1.47; P = .19). In-field relapses occurred in < 10% of the patients in each arm.For patients with stage I or II bulky mediastinal HL, no substantial statistically significant differences were detected between the two regimens, although power was limited. To the best of our knowledge, this is the first prospective trial reporting outcomes specific to this subgroup, and it sets a benchmark for comparison of ongoing and future studies.

    View details for DOI 10.1200/JCO.2014.57.8138

    View details for Web of Science ID 000355999800014

    View details for PubMedID 25897153

    View details for PubMedCentralID PMC4451176

  • Management of nodular lymphocyte predominant Hodgkin lymphoma HEMATOLOGICAL ONCOLOGY Advani, R. H., Hoppe, R. T. 2015; 33: 90-95

    View details for DOI 10.1002/hon.2226

    View details for Web of Science ID 000356094300017

    View details for PubMedID 26062064

  • Phase I/II study of intratumoral injection of SD-101, an immunostimulatory CpG, and intratumoral injection of ipillumumab, an anti-CTLA-4 monoclonal antibody, in combination with local radiation in low-grade B-cell lymphomas. Khodadoust, M., Chu, M., Czerwinski, D., McDonald, K., Long, S., Kohrt, H., Hoppe, R. T., Advani, R. H., Lowsky, R., Levy, R. AMER SOC CLINICAL ONCOLOGY. 2015
  • Value of Surveillance Studies for Patients With Stage I to II Diffuse Large B-Cell Lymphoma in the Rituximab Era. International journal of radiation oncology, biology, physics Hiniker, S. M., Pollom, E. L., Khodadoust, M. S., Kozak, M. M., Xu, G., Quon, A., Advani, R. H., Hoppe, R. T. 2015; 92 (1): 99-106

    Abstract

    The role of surveillance studies in limited-stage diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been well defined. We sought to evaluate the use of imaging (computed tomography [CT] and positron emission tomography [PET]-CT) scans and lactate dehydrogenase (LDH) in surveillance of patients with stage I to II DLBCL.A retrospective analysis was performed of patients who received definitive treatment between 2000 and 2013.One hundred sixty-two consecutive patients with stage I to II DLBCL were treated with chemotherapy +/- rituximab, radiation, or combined modality therapy. The 5-year rates of overall survival (OS) and freedom from progression (FFP) were 81.2% and 80.8%, respectively. Of the 162 patients, 124 (77%) were followed up with at least 1 surveillance PET scan beyond end-of-treatment scans; of those, 94 of 124 (76%) achieved a complete metabolic response on PET scan after completion of chemotherapy, and this was associated with superior FFP (P=.01, HR=0.3) and OS (P=.01, HR 0.3). Eighteen patients experienced relapse after initial response to therapy. Nine relapses were initially suspected by surveillance imaging studies (8 PET, 1 CT), and 9 were suspected clinically (5 by patient-reported symptoms and 4 by symptoms and physical examination). No relapses were detected by surveillance LDH. The median duration from initiation of treatment to relapse was 14.3 months among patients with relapses suspected by imaging, and 59.8 months among patients with relapses suspected clinically (P=.077). There was no significant difference in OS from date of first therapy or OS after relapse between patients whose relapse was suspected by imaging versus clinically. Thirteen of 18 patients underwent successful salvage therapy after relapse.A complete response on PET scan immediately after initial chemotherapy is associated with superior FFP and OS in stage I to II DLBCL. The use of PET scans as posttreatment surveillance is not associated with a survival advantage. LDH is not a sensitive marker for relapse. Our results argue for limiting the use of posttreatment surveillance in patients with limited-stage DLBCL.

    View details for DOI 10.1016/j.ijrobp.2015.01.039

    View details for PubMedID 25863757

  • The Paris Conference "La Radiothérapie de la Maladie de Hodgkin": A First Step in the Cure of Hodgkin Disease. International journal of radiation oncology, biology, physics Hoppe, R. T., Rosenberg, S. A. 2015; 92 (1): 3-4

    View details for DOI 10.1016/j.ijrobp.2015.01.027

    View details for PubMedID 25863747

  • Modern Radiation Therapy for Extranodal Lymphomas: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Yahalom, J., Illidge, T., Specht, L., Hoppe, R. T., Li, Y., Tsang, R., Wirth, A., Int Lymphoma Radiation Oncology Gr 2015; 92 (1): 11–31

    Abstract

    Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL). Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL), consolidation after systemic therapy, salvage treatment, or palliation. The wide range of presentations of ENL, involving any organ in the body and the spectrum of histological sub-types, poses a challenge both for routine clinical care and for the conduct of prospective and retrospective studies. This has led to uncertainty and lack of consistency in RT approaches between centers and clinicians. Thus far there is a lack of guidelines for the use of RT in the management of ENL. This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL, and to address the technical challenges of simulation, volume definition and treatment planning for the most frequently involved organs. Specifically, detailed recommendations for RT volumes are provided. We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL. We have adopted RT volume definitions based on the International Commission on Radiation Units and Measurements (ICRU), as has been widely adopted by the field of radiation oncology for solid tumors. Organ-specific recommendations take into account histological subtype, anatomy, the treatment intent, and other treatment modalities that may be have been used before RT.

    View details for PubMedID 25863750

  • Hodgkin Lymphoma, Version 2.2015 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Hoppe, R. T., Advani, R. H., Ai, W. Z., Ambinder, R. F., Aoun, P., Bello, C. M., Benitez, C. M., Bierman, P. J., Blum, K. A., Chen, R., Dabaja, B., Forero, A., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Hochberg, E. P., Huang, J., Johnston, P. B., Khan, N., Maloney, D. G., Mauch, P. M., Metzger, M., Moore, J. O., Morgan, D., Moskowitz, C. H., Mulroney, C., Poppe, M., Rabinovitch, R., Seropian, S., Tsien, C., Winter, J. N., Yahalom, J., Burns, J. L., Sundar, H. 2015; 13 (5): 554-586

    Abstract

    Hodgkin lymphoma (HL) is an uncommon malignancy involving lymph nodes and the lymphatic system. Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma are the 2 main types of HL. CHL accounts for most HL diagnosed in the Western countries. Chemotherapy or combined modality therapy, followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale), is the standard initial treatment for patients with newly diagnosed CHL. Brentuximab vedotin, a CD30-directed antibody-drug conjugate, has produced encouraging results in the treatment of relapsed or refractory disease. The potential long-term effects of treatment remain an important consideration, and long-term follow-up is essential after completion of treatment.

    View details for Web of Science ID 000354283800008

    View details for PubMedID 25964641

    View details for PubMedCentralID PMC4898052

  • Expert Radiation Oncologist Interpretations of Involved-Site Radiation Therapy Guidelines in the Management of Hodgkin Lymphoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hoppe, B. S., Hoppe, R. T. 2015; 92 (1): 40-45

    Abstract

    Recently, involved-site radiation therapy (ISRT) guidelines have been developed and published to replace the previous concept of involved-field radiation therapy for patients with lymphoma. However, these ISRT guidelines may be interpreted in different ways, posing difficulties for prospective clinical trials. This study reports survey results regarding interpretation of the ISRT guidelines.Forty-four expert lymphoma radiation oncologists were asked to participate in a survey that included 7 different cases associated with 9 questions. The questions pertained to ISRT contouring and asked respondents to choose between 2 different answers (no "correct" answer) and a third write-in option allowed.Fifty-two percent of those surveyed responded to the questionnaire. Among those who responded, 72% have practiced for >10 years, 46% have treated >20 Hodgkin lymphoma cases annually, and 100% were familiar with the ISRT concept. Among the 9 questions associated with the 7 cases, 3 had concordance among the expert radiation oncologists of greater than 70%. Six of the questions had less than 70% concordance (range, 56%-67%).Even among expert radiation oncologists, interpretation of ISRT guidelines is variable. Further guidance for ISRT field design will be needed to reduce variability among practicing physicians.

    View details for DOI 10.1016/j.ijrobp.2015.02.008

    View details for Web of Science ID 000353988200007

    View details for PubMedID 25863752

  • Modern Radiation Therapy for Primary Cutaneous Lymphomas: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Specht, L., Dabaja, B., Illidge, T., Wilson, L. D., Hoppe, R. T. 2015; 92 (1): 32-39

    Abstract

    Primary cutaneous lymphomas are a heterogeneous group of diseases. They often remain localized, and they generally have a more indolent course and a better prognosis than lymphomas in other locations. They are highly radiosensitive, and radiation therapy is an important part of the treatment, either as the sole treatment or as part of a multimodality approach. Radiation therapy of primary cutaneous lymphomas requires the use of special techniques that form the focus of these guidelines. The International Lymphoma Radiation Oncology Group has developed these guidelines after multinational meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the International Lymphoma Radiation Oncology Group steering committee on the use of radiation therapy in primary cutaneous lymphomas in the modern era.

    View details for DOI 10.1016/j.ijrobp.2015.01.008

    View details for Web of Science ID 000353988200006

    View details for PubMedID 25863751

  • Management of Nodular Lymphocyte Predominant Hodgkin Lymphoma in the Modern Era INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS King, M. T., Donaldson, S. S., Link, M. P., Natkunam, Y., Advani, R. H., Hoppe, R. T. 2015; 92 (1): 67-75

    Abstract

    To analyze treatment outcomes for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) at a single institution.Patients with newly diagnosed NLPHL between 1996 and 2013 were reviewed retrospectively. Patients treated before 1996 were excluded because the majority received extended field radiation therapy (RT) alone.Fifty-five patients (22 ≤ 21 years old) were identified. The median follow-up time was 6.8 years. Among 37 patients with limited-stage (I-II) disease, treatments included involved field RT at a median dose of 36 Gy (n=9), rituximab monotherapy (n=9), observation (n=3), and response-adaptive therapy (n=16), in which the RT dose was reduced from 25.5 Gy to 15 Gy or was eliminated based on interim imaging after chemotherapy. The 5-year progression-free survival (PFS) was 76.4% (95% confidence interval [CI], 63.1-92.4). Nine patients experienced progression, including 5 receiving rituximab, 2 undergoing observation, and 2 receiving response-adaptive therapy. Rituximab was associated with an inferior PFS compared with RT alone (P=.02). The difference in PFS between response-adaptive therapy and RT alone was not statistically significant (P=.39). Among 18 patients with advanced-stage (III-IV) disease, treatments included chemotherapy alone (n=3), combined modality therapy (CMT) (n=2), response-adaptive therapy (n=2), rituximab (n=7), and observation (n=4). The 5-year PFS was 29.9% (CI, 13.3-67.4). Twelve patients experienced progression, including 1 receiving chemotherapy, 1 receiving CMT, 6 receiving rituximab, and 4 undergoing observation. There was no significant PFS difference between rituximab and non-rituximab therapies (P=.19) within the caveat of small sample sizes. In the entire cohort, 9 patients (3 with limited disease, 6 with advanced disease) experienced large cell transformation (LCT). Seven patients died; of those, 5 died with LCT.For limited disease, response-adaptive therapy demonstrated comparable outcomes with RT alone. Rituximab monotherapy resulted in inferior outcomes for limited disease and a high relapse rate for advanced disease.

    View details for DOI 10.1016/j.ijrobp.2015.02.001

    View details for Web of Science ID 000353988200011

    View details for PubMedID 25863755

  • Low-dose total skin electron beam therapy as an effective modality to reduce disease burden in patients with mycosis fungoides: Results of a pooled analysis from 3 phase-II clinical trials. Journal of the American Academy of Dermatology Hoppe, R. T., Harrison, C., Tavallaee, M., Bashey, S., Sundram, U., Li, S., Million, L., Dabaja, B., Gangar, P., Duvic, M., Kim, Y. H. 2015; 72 (2): 286-292

    Abstract

    Standard-dose (36-Gy) total skin electron beam therapy (TSEBT) is a highly effective treatment in mycosis fungoides. However, the regimen is time-intensive and may be associated with significant toxicity.We sought to evaluate the efficacy and tolerability associated with low-dose (12-Gy) TSEBT.Data from 3 clinical trials using low-dose (12-Gy) TSEBT were pooled. In all trials, TSEBT-naïve patients with stage IB to IIIA mycosis fungoides were treated with TSEBT (12 Gy, 1 Gy per fraction over 3 weeks). The primary end point was clinical response rate. Secondary end points included time to response and duration of clinical benefit.In all, 33 patients enrolled. Eighteen were male; stages were 22 IB, 2 IIA, 7 IIB, and 2 IIIA. Overall response rate was 88% (29/33), including 9 patients with complete response. Median time to response was 7.6 weeks (3-12.4 weeks). Median duration of clinical benefit was 70.7 weeks (95% confidence interval 41.8-133.8 weeks). Toxicities from TSEBT were mild and reversible.Conclusions are limited because of the small number of patients.Low-dose TSEBT provides reliable and rapid reduction of disease burden in patients with mycosis fungoides, which could be administered safely multiple times during the course of a patient's disease with acceptable toxicity profile.

    View details for DOI 10.1016/j.jaad.2014.10.014

    View details for PubMedID 25476993

  • Use of High-Throughput Sequencing (HTS) of TCR beta to Determine the Kinetics of Graft-Versus-Lymphoma (GVL) Effect and T-Cell Repertoire Profiles after Allogeneic Transplant Weng, W., Armstrong, R., Arai, S., Hoppe, R. T., Meyer, E. H., Kim, Y. H. AMER SOC HEMATOLOGY. 2014
  • Non-Myeloablative Allogeneic Transplantation Resulting in Clinical and Molecular Remission with Low Non-Relapse Mortality (NRM) in Patients with Advanced Stage Mycosis Fungoides (MF) and Sezary Syndrome (SS) Weng, W., Armstrong, R., Arai, S., Johnston, L., Laport, G. G., Lowsky, R., Miklos, D. B., Shizuru, J. A., Benjamin, J. E., Negrin, R. S., Reddy, S., Million, L., Hoppe, R. T., Kim, Y. H. AMER SOC HEMATOLOGY. 2014
  • Dose-Escalated, Intratumoral TLR9 Agonist and Low-Dose Radiation Induce Abscopal Effects in Follicular Lymphoma Kohrt, H. E., Chu, J., Brody, J., Czerwinski, D. K., Chester, C., Sadaram, M., Advani, R., Kim, Y. H., Hoppe, R. T., Knox, S. J., Wapnir, I., Tibshirani, R. J., Levy, R. AMER SOC HEMATOLOGY. 2014
  • Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides or Sezary Syndrome: Final Results Show Significant Clinical Activity and Suggest Correlation with CD30 Expression Kim, Y. H., Tavallaee, M., Rozati, S., Sundram, U., Salva, K., Wood, G. S., Li, S., Krathen, M., Nagpal, S., Reddy, S., Armstrong, R., Hoppe, R. T., Pulitzer, M., Advani, R. H., Horwitz, S. M. AMER SOC HEMATOLOGY. 2014
  • A Cutaneous Lymphoma International Consortium 'CLIC' study of Prognostic Parameters in Advanced Stages of Mycosis Fungoides and Sezary Syndrome: Progress Towards Establishing a Prognostic Index to Augment Clinical Staging Scarisbrick, J. J., Quaglino, P., Vermeer, M., Whittaker, S., Wood, G. S., Duvic, M., Prince, M., Horwitz, S. M., Hoppe, R. T., Porcu, P., Stadler, R., Evison, F., Kim, Y. H. AMER SOC HEMATOLOGY. 2014
  • Comment on: "clinical features, management, and prognosis of an international series of 161 patients with limited-stage diffuse large B-cell lymphoma of the bone (the IELSG-14 Study)". oncologist Hoppe, R., Illidge, T., Specht, L., Vogelius, I., Yahalom, J. 2014; 19 (12): 1289-?

    View details for DOI 10.1634/theoncologist.2014-0200

    View details for PubMedID 25480339

    View details for PubMedCentralID PMC4257744

  • Non-Hodgkin's Lymphomas, Version 4.2014. Journal of the National Comprehensive Cancer Network Zelenetz, A. D., Gordon, L. I., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Byrd, J. C., Czuczman, M. S., Fayad, L. E., Fisher, R. I., Glenn, M. J., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Rabinovitch, R., Reddy, N., Reid, E., Saad, A. A., Sokol, L., Swinnen, L. J., Tsien, C., Vose, J. M., Yahalom, J., Zafar, N., Dwyer, M., Sundar, H. 2014; 12 (9): 1282-1303

    Abstract

    Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer cells. Mantle cell lymphoma (MCL) accounts for approximately 6% of all newly diagnosed NHL cases. Radiation therapy with or without systemic therapy is a reasonable approach for the few patients who present with early-stage disease. Rituximab-based chemoimmunotherapy followed by high-dose therapy and autologous stem cell rescue (HDT/ASCR) is recommended for patients presenting with advanced-stage disease. Induction therapy followed by rituximab maintenance may provide extended disease control for those who are not candidates for HDT/ASCR. Ibrutinib, a Bruton tyrosine kinase inhibitor, was recently approved for the treatment of relapsed or refractory disease. This manuscript discusses the recommendations outlined in the NCCN Guidelines for NHL regarding the diagnosis and management of patients with MCL.

    View details for PubMedID 25190696

  • Low Dose (12 Gy) Total Skin Electron Beam Therapy (TSEBT) for Mycosis Fungoides (mf): Results of Three Phase 2 Clinical Trials 56th Annual Meeting of the American-Society-for-Radiation-Oncology Hoppe, R. T., Harrison, C., Tavallaee, M., Bashey, S., Li, S., Million, L., Dabaja, B., Duvic, M., Kim, Y. H. ELSEVIER SCIENCE INC. 2014: S151–S151
  • Feasibility of a Table-Top Total Body Irradiation Technique using Robotic Couch Motion Chin, E., Otto, K., Hoppe, R., Hsu, A., Loo, B., Million, L., Xing, L., Fahimian, B. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2014: 15

    View details for DOI 10.1118/1.4894898

    View details for Web of Science ID 000341068100118

  • Modern Radiation Therapy for Hodgkin Lymphoma: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group (ILROG) INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Specht, L., Yahalom, J., Illidge, T., Berthelsen, A. K., Constine, L. S., Eich, H. T., Girinsky, T., Hoppe, R. T., Mauch, P., Mikhaeel, N. G., Ng, A. 2014; 89 (4): 854-862

    Abstract

    Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced volumes and doses is addressed, integrating modern imaging with 3-dimensional (3D) planning and advanced techniques of treatment delivery. The previously applied extended field (EF) and original involved field (IF) techniques, which treated larger volumes based on nodal stations, have now been replaced by the use of limited volumes, based solely on detectable nodal (and extranodal extension) involvement at presentation, using contrast-enhanced computed tomography, positron emission tomography/computed tomography, magnetic resonance imaging, or a combination of these techniques. The International Commission on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom optimal imaging is available, is explained. A new concept, involved site radiation therapy (ISRT), is introduced as the standard conformal therapy for the scenario, commonly encountered, wherein optimal imaging is not available. There is increasing evidence that RT doses used in the past are higher than necessary for disease control in this era of combined modality therapy. The use of INRT and of lower doses in early-stage HL is supported by available data. Although the use of ISRT has not yet been validated in a formal study, it is more conservative than INRT, accounting for suboptimal information and appropriately designed for safe local disease control. The goal of modern smaller field radiation therapy is to reduce both treatment volume and treatment dose while maintaining efficacy and minimizing acute and late sequelae. This review is a consensus of the International Lymphoma Radiation Oncology Group (ILROG) Steering Committee regarding the modern approach to RT in the treatment of HL, outlining a new concept of ISRT in which reduced treatment volumes are planned for the effective control of involved sites of HL. Nodal and extranodal non-Hodgkin lymphomas (NHL) are covered separately by ILROG guidelines.

    View details for DOI 10.1016/j.ijrobp.2013.05.005

    View details for Web of Science ID 000338707700020

    View details for PubMedID 23790512

  • Non-Hodgkin's lymphomas, version 2.2014. Journal of the National Comprehensive Cancer Network Zelenetz, A. D., Gordon, L. I., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Bellam, N., Byrd, J. C., Czuczman, M. S., Fayad, L. E., Fisher, R. I., Glenn, M. J., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Rabinovitch, R., Reddy, N., Reid, E., Sokol, L., Swinnen, L. J., Tsien, C., Vose, J. M., Yahalom, J., Zafar, N., Dwyer, M., Sundar, H. 2014; 12 (6): 916-946

    Abstract

    Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer cells. Follicular lymphoma (FL) is the most common subtype of indolent NHL, accounting for approximately 22% of all newly diagnosed cases of NHL. The incorporation of rituximab to chemotherapy regimens has become a widely accepted standard of care for first-line therapy for patients with FL. Maintenance and consolidation therapy with rituximab and radioimmunotherapy have also been associated with improved progression-free survival in patients experiencing response to first-line therapy. Despite therapeutic advances that have improved outcomes, FL is generally considered a chronic disease characterized by multiple recurrences with current therapies. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with FL.

    View details for PubMedID 24925202

  • Non-Hodgkin's Lymphomas, Version 2.2014. Journal of the National Comprehensive Cancer Network Zelenetz, A. D., Gordon, L. I., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Bellam, N., Byrd, J. C., Czuczman, M. S., Fayad, L. E., Fisher, R. I., Glenn, M. J., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Rabinovitch, R., Reddy, N., Reid, E., Sokol, L., Swinnen, L. J., Tsien, C., Vose, J. M., Yahalom, J., Zafar, N., Dwyer, M., Sundar, H. 2014; 12 (6): 916-946

    View details for PubMedID 24925202

  • Value of surveillance studies for patients (pts) with stage I-II diffuse large B-cell lymphoma (DLBCL) in the rituximab (R) era. Hiniker, S. M., Pollom, E. L., Khodadoust, M. S., Kozak, M. M., Advani, R. H., Hoppe, R. T. AMER SOC CLINICAL ONCOLOGY. 2014
  • Histologic subtypes of breast cancer following radiotherapy for Hodgkin lymphoma. Annals of oncology Horst, K. C., Hancock, S. L., OGNIBENE, G., Chen, C., Advani, R. H., Rosenberg, S. A., Donaldson, S. S., Hoppe, R. T. 2014; 25 (4): 848-851

    Abstract

    The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC.We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs.One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003).BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.

    View details for DOI 10.1093/annonc/mdu017

    View details for PubMedID 24608191

  • Mature results of a phase II study of rituximab therapy for nodular lymphocyte-predominant Hodgkin lymphoma. Journal of clinical oncology Advani, R. H., Horning, S. J., Hoppe, R. T., Daadi, S., Allen, J., Natkunam, Y., Bartlett, N. L. 2014; 32 (9): 912-918

    Abstract

    Universal expression of CD20 by malignant cells in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) led us to evaluate rituximab (R) as a therapeutic option.Patients with previously treated or newly diagnosed NLPHL were treated with R (375 mg/m(2) once per week for 4 weeks) or, after a protocol amendment, with R plus R maintenance (MR; administered once every 6 months for 2 years). Primary and secondary outcome measures were progression-free survival (PFS) and overall response rate (ORR), respectively.A total of 39 patients were enrolled (R, n = 23; R + MR, n = 16). After four once-per-week treatments, ORR was 100% (complete response, 67%; partial response, 33%). At median follow-ups of 9.8 years for R and 5 years for R + MR, median PFS were 3 and 5.6 years (P = .26), respectively; median overall survival (OS) was not reached. Estimated 5-year PFS and OS for patients treated with R versus R + MR were 39.1% (95% CI, 23.5 to 65.1) and 95.7% (95% CI, 87.7 to 100) versus 58.9% (95% CI, 38.0 to 91.2) and 85.7% (95% CI, 69.2 to 100), respectively. Nine of 23 patients experiencing relapse had evidence of transformation to aggressive B-cell lymphoma; six of these patients had infradiaphragmatic involvement at study entry.R is an active agent in NLPHL. Although responses are not durable in most patients, a significant minority experience remissions lasting > 5 years. R + MR results in a nonsignificant increase in PFS compared with R. R may be considered in the relapsed setting for NLPHL. The potential for transformation of NLPHL to aggressive B-cell lymphoma underscores the importance of rebiopsy and long-term follow-up.

    View details for DOI 10.1200/JCO.2013.53.2069

    View details for PubMedID 24516013

  • Mature Results of a Phase II Study of Rituximab Therapy for Nodular Lymphocyte-Predominant Hodgkin Lymphoma. Journal of clinical oncology Advani, R. H., Horning, S. J., Hoppe, R. T., Daadi, S., Allen, J., Natkunam, Y., Bartlett, N. L. 2014; 32 (9): 912-918

    View details for DOI 10.1200/JCO.2013.53.2069

    View details for PubMedID 24516013

  • Bulky Mediastinal Classical Hodgkin Lymphoma in Young Women ONCOLOGY-NEW YORK Percival, M. M., Hoppe, R. T., Advani, R. H. 2014; 28 (3): 253-+

    View details for Web of Science ID 000333550900015

    View details for PubMedID 24855735

  • Outcome of Tandem Autologous/Allogeneic Hematopoietic Cell Transplantation in High-Risk Non Hodgkin's Lymphoma Patients: Stanford University Experience Wudhikarn, K., Lavori, P., Arai, S., Johnston, L., Laport, G. G., Lowsky, R., Miklos, D. B., Shizuru, J. A., Hoppe, R. T., Benjamin, J., Meyer, E., Negrin, R., Weng, W. ELSEVIER SCIENCE INC. 2014: S164
  • How I treat nodular lymphocyte predominant Hodgkin lymphoma BLOOD Advani, R. H., Hoppe, R. T. 2013; 122 (26): 4182-4188

    Abstract

    Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon entity that, in contrast to classical Hodgkin lymphoma (cHL), universally expresses CD20, a hallmark of the disease. The majority of the patients present with early-stage disease, and treatment with local radiation provides excellent disease control and overall survival (OS). For locally extensive or advanced stages, paradigms used for cHL have been employed, with similar outcomes. Unlike cHL, late relapses may occur, as well as a propensity to transform to an aggressive B-cell non-Hodgkin lymphoma that underscores the importance of long-term follow-up and rebiopsy at the time of relapse. Deaths caused by NLPHL are uncommon, and in older series, secondary malignancies and other treatment-related toxicities contributed appreciably to overall mortality. Expression of CD20 in NLPHL has led to the evaluation of rituximab as a therapeutic option. Although results with single-agent rituximab in the front-line setting are inferior to conventional therapy, rituximab is a reasonable choice for relapsed disease because of the high overall response rate and excellent tolerability. Most patients have a long OS; therefore, overall goals of therapy should be to minimize the risk for relapse and long-term toxicity.

    View details for DOI 10.1182/blood-2013-07-453241

    View details for Web of Science ID 000329741000012

    View details for PubMedID 24215035

  • Minimal Residual Disease Monitoring with High-Throughput Sequencing of T Cell Receptors in Cutaneous T Cell Lymphoma SCIENCE TRANSLATIONAL MEDICINE Weng, W., Armstrong, R., Arai, S., Desmarais, C., Hoppe, R., Kim, Y. H. 2013; 5 (214)

    Abstract

    Mycosis fungoides (MF) and the leukemic presentation Sézary syndrome (SS) are clonal T cell lymphomas arising from the skin and are considered noncurable with standard therapies. To develop a specific and sensitive monitoring tool, we tested the ability of high-throughput sequencing (HTS) of T cell receptors (TCRB) to monitor minimal residual disease (MRD) after allogeneic hematopoietic cell transplantation. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) or skin samples. The rearranged TCRβ loci were amplified using Vβ- and Jβ-specific primers, followed by HTS, to generate up to 1,000,000 reads spanning the CDR3 region of individual cells. Malignant clones were identified in diagnostic samples in all cases by a dominant CDR3 sequence. Before transplant, four patients had circulating Sézary cells by the routine flow cytometry, which was confirmed by TCRB HTS. Although the flow cytometry found no detectable Sézary cells, malignant clones were detected by TCRB HTS in all other six cases. Five patients achieved "molecular remission" in blood between +30 and +540 days after transplant. Four of these patients also achieved molecular clearance in skin after transplant. Experiments using blood samples spiked with purified Sézary cells demonstrated that TCRB HTS can detect Sézary cells at the level of 1 in 50,000 PBMCs, which is more sensitive than standard diagnostics. We have thus demonstrated the utility of TCRB HTS to assess MRD with increased sensitivity and specificity compared to other current methodologies, and to monitor response to therapy in this MF/SS patient population.

    View details for Web of Science ID 000328057800011

    View details for PubMedID 24307695

  • Minimal residual disease monitoring with high-throughput sequencing of T cell receptors in cutaneous T cell lymphoma. Science translational medicine Weng, W., Armstrong, R., Arai, S., Desmarais, C., Hoppe, R., Kim, Y. H. 2013; 5 (214): 214ra171-?

    Abstract

    Mycosis fungoides (MF) and the leukemic presentation Sézary syndrome (SS) are clonal T cell lymphomas arising from the skin and are considered noncurable with standard therapies. To develop a specific and sensitive monitoring tool, we tested the ability of high-throughput sequencing (HTS) of T cell receptors (TCRB) to monitor minimal residual disease (MRD) after allogeneic hematopoietic cell transplantation. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) or skin samples. The rearranged TCRβ loci were amplified using Vβ- and Jβ-specific primers, followed by HTS, to generate up to 1,000,000 reads spanning the CDR3 region of individual cells. Malignant clones were identified in diagnostic samples in all cases by a dominant CDR3 sequence. Before transplant, four patients had circulating Sézary cells by the routine flow cytometry, which was confirmed by TCRB HTS. Although the flow cytometry found no detectable Sézary cells, malignant clones were detected by TCRB HTS in all other six cases. Five patients achieved "molecular remission" in blood between +30 and +540 days after transplant. Four of these patients also achieved molecular clearance in skin after transplant. Experiments using blood samples spiked with purified Sézary cells demonstrated that TCRB HTS can detect Sézary cells at the level of 1 in 50,000 PBMCs, which is more sensitive than standard diagnostics. We have thus demonstrated the utility of TCRB HTS to assess MRD with increased sensitivity and specificity compared to other current methodologies, and to monitor response to therapy in this MF/SS patient population.

    View details for DOI 10.1126/scitranslmed.3007420

    View details for PubMedID 24307695

  • Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience. Blood Tan, D., Horning, S. J., Hoppe, R. T., Levy, R., Rosenberg, S. A., Sigal, B. M., Warnke, R. A., Natkunam, Y., Han, S. S., Yuen, A., Plevritis, S. K., Advani, R. H. 2013; 122 (6): 981-987

    Abstract

    Recent studies report an improvement in overall survival (OS) of patients with follicular lymphoma (FL). Previously untreated patients with grade 1-2 FL referred from 1960-2003 and treated at Stanford were identified. Four eras were considered: era 1, pre-anthracycline (1960-1975, n=180); era 2, anthracycline (1976-1986, n=426), era 3, aggressive chemotherapy/purine analogs (1987-1996, n=471) and era 4, rituximab (1997-2003, n=257). Clinical characteristics, patterns of care and survival outcomes were assessed. Observed OS was compared with the expected OS calculated from Berkeley Mortality Database life tables derived from population matched by gender and age at time of diagnosis. The median OS was 13.6 years. Age, gender and stage did not differ across the eras. Although primary treatment varied, event free survival after the first treatment did not differ between eras (p=0.17). Median OS improved from approximately 11 years in eras 1 and 2 to 18.4 years in era 3 and has not yet been reached for era 4 (p<0.001) with no suggestion of a plateau in any era. These improvements in OS exceeded improvements in survival in the general population during the same time period. Several factors, including better supportive care and effective therapies for relapsed disease, are likely responsible for this improvement.

    View details for DOI 10.1182/blood-2013-03-491514

    View details for PubMedID 23777769

  • Low-dose radiation therapy (2 Gy × 2) in the treatment of orbital lymphoma. International journal of radiation oncology, biology, physics Fasola, C. E., Jones, J. C., Huang, D. D., Le, Q., Hoppe, R. T., Donaldson, S. S. 2013; 86 (5): 930-935

    Abstract

    Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa.We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR).At a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity.Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.

    View details for DOI 10.1016/j.ijrobp.2013.04.035

    View details for PubMedID 23726002

  • Low-Dose Radiation Therapy (2 Gy x 2) in the Treatment of Orbital Lymphoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Fasola, C. E., Jones, J. C., Huang, D. D., Quynh-Thu Le, Q. T., Hoppe, R. T., Donaldson, S. S. 2013; 86 (5): 930-935

    Abstract

    Low-dose radiation has become increasingly used in the management of indolent non-Hodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa.We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR).At a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity.Low-dose radiation with 2 Gy × 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse.

    View details for DOI 10.1016/j.ijrobp.2013.04.035

    View details for Web of Science ID 000321743600028

  • Evolution of the techniques of radiation therapy in the management of lymphoma INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY Hoppe, R. T. 2013; 18 (3): 359-363

    Abstract

    Radiation techniques for the treatment of Hodgkin's disease have evolved dramatically in the past century. Shortly after the discovery of X-rays, the lymphomas in general, and Hodgkin's disease in particular, were noted to be radiosensitive. However, equipment limitations restricted the ability to administer sufficient doses to adequate depth to ensure long-term control. This situation improved sequentially with the development of the Coolidge tube, (60)Co machine, and medical linear accelerators. With megavoltage radiation it was possible to demonstrate cures of stage I-II disease with high-dose extended-field irradiation. When combined modality therapy programs were introduced, this permitted restriction of radiation fields and doses in order to decrease toxicity. Innovative advanced technologies such as PET simulation, 3-D treatment planning, intensity-modulated radiotherapy, active breathing control, and proton therapy have further improved the outcomes for patients treated with irradiation.

    View details for DOI 10.1007/s10147-013-0556-3

    View details for Web of Science ID 000320456500002

    View details for PubMedID 23575469

  • Efficacy of abbreviated Stanford V chemotherapy and involved-field radiotherapy in early-stage Hodgkin lymphoma: mature results of the G4 trial ANNALS OF ONCOLOGY Advani, R. H., Hoppe, R. T., Baer, D., Mason, J., Warnke, R., Allen, J., Daadi, S., Rosenberg, S. A., Horning, S. J. 2013; 24 (4): 1044-1048

    Abstract

    To assess the efficacy of an abbreviated Stanford V regimen in patients with early-stage Hodgkin lymphoma (HL). PATIENTS AND METHODS PATIENTS: with untreated nonbulky stage I-IIA supradiaphragmatic HL were eligible for the G4 study. Stanford V chemotherapy was administered for 8 weeks followed by radiation therapy (RT) 30 Gy to involved fields (IF). Freedom from progression (FFP), disease-specific survival (DSS) and overall survival (OS) were estimated.All 87 enrolled patients completed the abbreviated regimen. At a median follow-up of 10 years, FFP, DSS and OS are 94%, 99% and 94%, respectively. Therapy was well tolerated with no treatment-related deaths.Mature results of the abbreviated Stanford V regimen in nonbulky early-stage HL are excellent and comparable to the results from other contemporary therapies.

    View details for DOI 10.1093/annonc/mds542

    View details for PubMedID 23136225

  • The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496 BRITISH JOURNAL OF HAEMATOLOGY Evens, A. M., Hong, F., Gordon, L. I., Fisher, R. I., Bartlett, N. L., Connors, J. M., Gascoyne, R. D., Wagner, H., Gospodarowicz, M., Cheson, B. D., Stiff, P. J., Advani, R., Miller, T. P., Hoppe, R. T., Kahl, B. S., Horning, S. J. 2013; 161 (1): 76-86

    Abstract

    There is a lack of contemporary prospective data examining the adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) and Stanford V (SV; doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone) regimens in older Hodgkin lymphoma (HL) patients. Forty-four advanced-stage, older HL patients (aged ≥60 years) were treated on the randomized study, E2496. Toxicities were mostly similar between chemotherapy regimens, although 24% of older patients developed bleomycin lung toxicity (BLT), which occurred mainly with ABVD (91%). Further, the BLT-related mortality rate was 18%. The overall treatment-related mortality for older HL patients was 9% vs. 0·3% for patients aged <60 years (P < 0·001). Among older patients, there were no survival differences between ABVD and SV. According to age, outcomes were significantly inferior for older versus younger patients (5-year failure-free survival: 48% vs. 74%, respectively, P = 0·002; 5-year overall survival: 58% and 90%, respectively, P < 0·0001), although time-to-progression (TTP) was not significantly different (5-year TTP: 68% vs. 78%, respectively, P = 0·37). Furthermore, considering progression and death without progression as competing risks, the risk of progression was not different between older and younger HL patients (5 years: 30% and 23%, respectively, P = 0·30); however, the incidence of death without progression was significantly increased for older HL patients (22% vs. 9%, respectively, P < 0·0001). Altogether, the marked HL age-dependent survival differences appeared attributable primarily to non-HL events.

    View details for DOI 10.1111/bjh.12222

    View details for Web of Science ID 000316333300009

    View details for PubMedID 23356491

  • Non-Hodgkin's Lymphomas, Version 1.2013 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Zelenetz, A. D., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Bellam, N., Byrd, J. C., Czuczman, M. S., Fayad, L. E., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Pro, B., Reddy, N., Sokol, L., Swinnen, L., Tsien, C., Vose, J. M., Yahalom, J., Zafar, N., Dwyer, M. A., Naganuma, M. 2013; 11 (3): 257-273

    Abstract

    These NCCN Guidelines Insights summarize several key updates to the NCCN Guidelines for Non-Hodgkin's Lymphomas (NHL) and provide a discussion of the clinical evidence that support the updates. The updates discussed in this article feature recommendations for additional treatment options in patients with chronic lymphocytic leukemia and guidance surrounding the management of hepatitis virus reactivation/infections in high-risk patients with NHL undergoing antitumor therapy.

    View details for Web of Science ID 000316037400005

  • Randomized Phase III Trial of ABVD Versus Stanford V With or Without Radiation Therapy in Locally Extensive and Advanced-Stage Hodgkin Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperative Oncology Group (E2496) JOURNAL OF CLINICAL ONCOLOGY Gordon, L. I., Hong, F., Fisher, R. I., Bartlett, N. L., Connors, J. M., Gascoyne, R. D., Wagner, H., Stiff, P. J., Cheson, B. D., Gospodarowicz, M., Advani, R., Kahl, B. S., Friedberg, J. W., Blum, K. A., Habermann, T. M., Tuscano, J. M., Hoppe, R. T., Horning, S. J. 2013; 31 (6): 684-691

    Abstract

    Although ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been established as the standard of care in patients with advanced Hodgkin lymphoma, newer regimens have been investigated, which have appeared superior in early phase II studies. Our aim was to determine if failure-free survival was superior in patients treated with the Stanford V regimen compared with ABVD.The Eastern Cooperative Oncology Group, along with the Cancer and Leukemia Group B, the Southwest Oncology Group, and the Canadian NCIC Clinical Trials Group, conducted this randomized phase III trial in patients with advanced Hodgkin lymphoma. Stratification factors included extent of disease (localized v extensive) and International Prognostic Factors Project Score (0 to 2 v 3 to 7). The primary end point was failure-free survival (FFS), defined as the time from random assignment to progression, relapse, or death, whichever occurred first. Overall survival, a secondary end point, was measured from random assignment to death as a result of any cause. This design provided 87% power to detect a 33% reduction in FFS hazard rate, or a difference in 5-year FFS of 64% versus 74% at two-sided .05 significance level.There was no significant difference in the overall response rate between the two arms, with complete remission and clinical complete remission rates of 73% for ABVD and 69% for Stanford V. At a median follow-up of 6.4 years, there was no difference in FFS: 74% for ABVD and 71% for Stanford V at 5 years (P = .32).ABVD remains the standard of care for patients with advanced Hodgkin lymphoma.

    View details for DOI 10.1200/JCO.2012.43.4803

    View details for Web of Science ID 000315086400016

    View details for PubMedID 23182987

    View details for PubMedCentralID PMC3574266

  • Risk of Therapy-Related Secondary Leukemia in Hodgkin Lymphoma: The Stanford University Experience Over Three Generations of Clinical Trials JOURNAL OF CLINICAL ONCOLOGY Koontz, M. Z., Horning, S. J., Balise, R., Greenberg, P. L., Rosenberg, S. A., Hoppe, R. T., Advani, R. H. 2013; 31 (5): 592-598

    Abstract

    To assess therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) risk in patients treated for Hodgkin lymphoma (HL) on successive generations of Stanford clinical trials.Patients with HL treated at Stanford with at least 5 years of follow-up after completing therapy were identified from our database. Records were reviewed for outcome and development of t-AML/MDS.Seven hundred fifty-four patients treated from 1974 to 2003 were identified. Therapy varied across studies. Radiotherapy evolved from extended fields (S and C studies) to involved fields (G studies). Primary chemotherapy was mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or procarbazine, mechlorethamine, and vinblastine (PAVe) in S studies; MOPP, PAVe, vinblastine, bleomycin, and methotrexate (VBM), or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in C studies; and VbM (reduced dose of bleomycin compared with VBM) or mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) in G studies. Cumulative exposure to alkylating agent (AA) was notably lower in the G studies compared with the S and C studies, with a 75% to 83% lower dose of nitrogen mustard in addition to omission of procarbazine and melphalan. Twenty-four (3.2%) of 754 patients developed t-AML/MDS, 15 after primary chemotherapy and nine after salvage chemotherapy for relapsed HL. The incidence of t-AML/MDS was significantly lower in the G studies (0.3%) compared with the S (5.7%) or C (5.2%) studies (P < .001). Additionally, in the G studies, no t-AML/MDS was noted after primary therapy, and the only patient who developed t-AML/MDS did so after second-line therapy.Our data demonstrate the relationship between the cumulative AA dose and t-AML/MDS. Limiting the dose of AA and decreased need for secondary treatments have significantly reduced the incidence of t-AML/MDS, which was extremely rare in the G studies (Stanford V era).

    View details for DOI 10.1200/JCO.2012.44.5791

    View details for PubMedID 23295809

  • Non-Hodgkin's Lymphomas, Version 3.2012 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Zelenetz, A. D., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Bellam, N., Byrd, J. C., Czuczman, M. S., Fayad, L., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Pro, B., Reddy, N., Sokol, L., Swinnen, L., Tsien, C., Vose, J. M., Yahalom, J., Zafar, N., Naganuma, M., Dwyer, M. A. 2012; 10 (12): 1487-1498

    Abstract

    These NCCN Guidelines Insights summarize several key updates to the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin's Lymphomas (NHL) and describe the clinical evidence supporting the updates. The featured updates include changes to the recommendations for treatment options in patients with chronic lymphocytic leukemia (including in elderly or frail patients and patients with poor-risk cytogenetics), guidance surrounding surveillance imaging for follow-up of patients with NHL, and the addition of first-line consolidation options for patients with mantle cell lymphoma.

    View details for Web of Science ID 000312114200005

  • Point/counterpoint: early-stage Hodgkin lymphoma and the role of radiation therapy HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM Meyer, R. M., Hoppe, R. T. 2012: 313-321

    Abstract

    The results of recent clinical trials for the management of limited-stage Hodgkin lymphoma have led to considerable debate, especially regarding the role of radiation therapy. This review highlights those recent trials and provides perspectives regarding their interpretation from a radiation oncologist and a hematologist. The trial protocol is available at http://www.nejm.org/doi/suppl/10.1056/NEJMoa1111961/suppl_file/nejmoa1111961_protocol.pdf.

    View details for DOI 10.1182/asheducation-2012.1.313

    View details for Web of Science ID 000323755900046

  • Point/counterpoint: early-stage Hodgkin lymphoma and the role of radiation therapy BLOOD Meyer, R. M., Hoppe, R. T. 2012; 120 (23): 4488-4495

    Abstract

    The results of recent clinical trials for the management of limited-stage Hodgkin lymphoma have led to considerable debate, especially regarding the role of radiation therapy. This review highlights those recent trials and provides perspectives regarding their interpretation from a radiation oncologist and a hematologist. The trial protocol is available at http://www.nejm.org/doi/suppl/10.1056/NEJMoa1111961/suppl_file/nejmoa1111961_protocol.pdf.

    View details for DOI 10.1182/blood-2012-05-423236

    View details for Web of Science ID 000313113300011

    View details for PubMedID 22821764

    View details for PubMedCentralID PMC3512228

  • in Situ Vaccination for Patients with Previously Untreated Follicular Lymphoma: Analysis of Immune Responses 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Czerwinski, D. K., Brody, J., Kohrt, H. E., Hoppe, R. T., Advani, R. H., Levy, R. AMER SOC HEMATOLOGY. 2012
  • Brentuximab Vedotin Demonstrates Significant Clinical Activity in Relapsed or Refractory Mycosis Fungoides with Variable CD30 Expression 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Krathen, M., Sundram, U., Bashey, S., Sutherland, K., Salva, K., Wood, G. S., Advani, R. H., Hoppe, R. T., Reddy, S., Armstrong, R., Nagpal, S., Pulitzer, M., Horwitz, S. M., Kim, Y. H. AMER SOC HEMATOLOGY. 2012
  • Second Cancers After Treatment with Stanford V Regimen in Eastern Cooperative Oncology Group (ECOG) Pilot Study E1492 At a Median Follow up of 17 Years 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Advani, R. H., Li, H., Hoppe, R. T., Bartlett, N. L., Bennett, J. M., Neuberg, D. S., Cassileth, P. A., Kahl, B. S., Horning, S. J. AMER SOC HEMATOLOGY. 2012
  • Long-term outcomes after high dose therapy and autologous haematopoietic cell rescue for refractory/relapsed Hodgkin lymphoma BRITISH JOURNAL OF HAEMATOLOGY Minn, A. Y., Riedel, E., Halpern, J., Johnston, L. J., Horning, S. J., Hoppe, R. T., Goodman, K. A. 2012; 159 (3): 329-339

    Abstract

    The standard treatment for patients with refractory or relapsed Hodgkin lymphoma (HL) is high-dose chemotherapy and/or radiation with autologous haematopoietic cell rescue (AHCR). In this study, we assessed quality of life and evaluated the risk of late morbidity and mortality for HL patients who underwent AHCR. One hundred and fifty-four patients who underwent AHCR at Stanford University from 1988 to 2002 and survived ≥2 years were evaluated. Median follow-up was 10·2 years. There were 54 deaths, 34 from HL, 20 from other causes. The 10-year cumulative incidence of death from HL or other causes was 21·7% and 12·7%, respectively. Thirteen deaths were from second malignancies. The risk ratio of second malignancies was 8·0 [95% confidence interval (CI), 4·7-12·6] compared with the general population, and 3·0 (95% CI, 1·8-4·8) compared with HL patients not undergoing AHCR. The risk ratio of second malignancies was 1·5 (95% CI, 0·9-2·4) compared with HL patients receiving non-AHCR therapy. Overall quality of life did not differ from the general population, but AHCR survivors did note reduced functioning and some worse symptoms. AHCR survivors may be at increased risk of death from HL and other causes compared with the general population, but not compared with the HL population as a whole.

    View details for DOI 10.1111/bjh.12038

    View details for Web of Science ID 000309717500009

    View details for PubMedID 22966754

  • A Tribute to Malcolm A. Bagshaw-An Innovative Physician Who Soared to Success INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hoppe, R. T., Donaldson, S. S. 2012; 83 (1): 6-7

    View details for DOI 10.1016/j.ijrobp.2012.02.010

    View details for Web of Science ID 000302993900023

    View details for PubMedID 22516381

  • Exploratory study of brentuximab vedotin (SGN-35), a novel monoclonal antibody-drug-conjugate against CD30, in mycosis fungoides (MF) and Sezary syndrome (SS) demonstrates clinical responses regardless of CD30 expression levels 75th Annual Meeting of the Society-for-Investigative-Dermatology Bashey, S., Krathen, M., Sutherland, K., Sundram, U., Lingala, B., Horwitz, S., Hoppe, R., Pulitzer, M., Advani, R., Kim, Y. NATURE PUBLISHING GROUP. 2012: S95–S95
  • Hodgkin Lymphoma, Version 2.2012 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Hoppe, R. T., Advani, R. H., Ai, W. Z., Ambinder, R. F., Aoun, P., Bello, C. M., Bierman, P. J., Blum, K. A., Chen, R., Dabaja, B., Duron, Y., Forero, A., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Hochberg, E. P., Maloney, D. G., Mansur, D., Mauch, P. M., Metzger, M., Moore, J. O., Morgan, D., Moskowitz, C. H., Poppe, M., Pro, B., Winter, J. N., Yahalom, J., Sundar, H. 2012; 10 (5): 589-597

    Abstract

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin Lymphoma (HL) include the clinical management of classical HL and lymphocyte-predominant HL (LPHL). Major changes have been incorporated into these guidelines since their inception. In the 2012 NCCN Guidelines for HL, PET scans are not recommended for interim restaging of patients with stage I to II favorable disease. After reevaluating the available evidence on the use of interim PET imaging, the panel recommends the use of diagnostic CT scan of involved sites for interim restaging after completion of chemotherapy for this group of patients. Maintenance rituximab for 2 years is included as an option for patients with stage IB to IIB or stage III to IV LPHL treated with rituximab alone in the first-line setting. Brentuximab vedotin is included as an option for patients with progressive disease or relapsed disease after second-line chemotherapy or high-dose therapy with autologous stem cell rescue.

    View details for Web of Science ID 000303557700005

    View details for PubMedID 22570290

  • Interim-treatment quantitative PET parameters predict progression and death among patients with hodgkin's disease RADIATION ONCOLOGY Tseng, D., Rachakonda, L. P., Su, Z., Advani, R., Horning, S., Hoppe, R. T., Quon, A., Graves, E. E., Loo, B. W., Tran, P. T. 2012; 7

    Abstract

    We hypothesized that quantitative PET parameters may have predictive value beyond that of traditional clinical factors such as the International Prognostic Score (IPS) among Hodgkin's disease (HD) patients.Thirty HD patients treated at presentation or relapse had staging and interim-treatment PET-CT scans. The majority of patients (53%) had stage III-IV disease and 67% had IPS ≥ 2. Interim-treatment scans were performed at a median of 55 days from the staging PET-CT. Chemotherapy regimens used: Stanford V (67%), ABVD (17%), VAMP (10%), or BEACOPP (7%). Hypermetabolic tumor regions were segmented semiautomatically and the metabolic tumor volume (MTV), mean standardized uptake value (SUV mean), maximum SUV (SUV max) and integrated SUV (iSUV) were recorded. We analyzed whether IPS, absolute value PET parameters or the calculated ratio of interim- to pre-treatment PET parameters were associated with progression free survival (PFS) or overall survival (OS).Median follow-up of the study group was 50 months. Six of the 30 patients progressed clinically. Absolute value PET parameters from pre-treatment scans were not significant. Absolute value SUV max from interim-treatment scans was associated with OS as determined by univariate analysis (p < 0.01). All four calculated PET parameters (interim/pre-treatment values) were associated with OS: MTV int/pre (p < 0.01), SUV mean int/pre (p < 0.05), SUV max int/pre (p = 0.01), and iSUV int/pre (p < 0.01). Absolute value SUV max from interim-treatment scans was associated with PFS (p = 0.01). Three calculated PET parameters (int/pre-treatment values) were associated with PFS: MTV int/pre (p = 0.01), SUV max int/pre (p = 0.02) and iSUV int/pre (p = 0.01). IPS was associated with PFS (p < 0.05) and OS (p < 0.01).Calculated PET metrics may provide predictive information beyond that of traditional clinical factors and may identify patients at high risk of treatment failure early for treatment intensification.

    View details for DOI 10.1186/1748-717X-7-5

    View details for PubMedID 22260710

  • In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study BLOOD Kim, Y. H., Gratzinger, D., Harrison, C., Brody, J. D., Czerwinski, D. K., Ai, W. Z., Morales, A., Abdulla, F., Xing, L., Navi, D., Tibshirani, R. J., Advani, R. H., Lingala, B., Shah, S., Hoppe, R. T., Levy, R. 2012; 119 (2): 355-363

    Abstract

    We have developed and previously reported on a therapeutic vaccination strategy for indolent B-cell lymphoma that combines local radiation to enhance tumor immunogenicity with the injection into the tumor of a TLR9 agonist. As a result, antitumor CD8(+) T cells are induced, and systemic tumor regression was documented. Because the vaccination occurs in situ, there is no need to manufacture a vaccine product. We have now explored this strategy in a second disease: mycosis fungoides (MF). We treated 15 patients. Clinical responses were assessed at the distant, untreated sites as a measure of systemic antitumor activity. Five clinically meaningful responses were observed. The procedure was well tolerated and adverse effects consisted mostly of mild and transient injection site or flu-like symptoms. The immunized sites showed a significant reduction of CD25(+), Foxp3(+) T cells that could be either MF cells or tissue regulatory T cells and a similar reduction in S100(+), CD1a(+) dendritic cells. There was a trend toward greater reduction of CD25(+) T cells and skin dendritic cells in clinical responders versus nonresponders. Our in situ vaccination strategy is feasible also in MF and the clinical responses that occurred in a subset of patients warrant further study with modifications to augment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993.

    View details for DOI 10.1182/blood-2011-05-355222

    View details for PubMedID 22045986

  • STAGE I-IIIA NON-BULKY HODGKIN'S LYMPHOMA. IS FURTHER DISTINCTION BASED ON PROGNOSTIC FACTORS USEFUL? THE STANFORD EXPERIENCE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Advani, R. H., Hoppe, R. T., Maeda, L. S., Baer, D. M., Mason, J., Rosenberg, S. A., Horning, S. J. 2011; 81 (5): 1374-1379

    Abstract

    In the United States, early-stage Hodgkin's lymphoma (HL) is defined as asymptomatic stage I/II non-bulky disease. European groups stratify patients to more intense treatment by considering additional unfavorable factors, such as age, number of nodal sites, sedimentation rate, extranodal disease, and elements of the international prognostic score for advanced HL. We sought to determine the prognostic significance of these factors in patients with early-stage disease treated at Stanford University Medical Center.This study was a retrospective analysis of 101 patients treated with abbreviated Stanford V chemotherapy (8 weeks) and 30-Gy (n=84 patients) or 20-Gy (n=17 patients) radiotherapy to involved sites. Outcomes were assessed after applying European risk factors.At a median follow-up of 8.5 years, freedom from progression (FFP) and overall survival (OS) rates were 94% and 97%, respectively. From 33% to 60% of our patients were unfavorable per European criteria (i.e., German Hodgkin Study Group [GHSG], n=55%; European Organization for Research and Treatment of Cancer, n=33%; and Groupe d'Etudes des Lymphomes de l'Adulte, n=61%). Differences in FFP rates between favorable and unfavorable patients were significant only for GHSG criteria (p=0.02) with there were no differences in OS rates for any criteria. Five of 6 patients who relapsed were successfully salvaged.The majority of our patients deemed unfavorable had an excellent outcome despite undergoing a significantly abbreviated regimen. Application of factors used by the GHSG defined a less favorable subset for FFP but with no impact on OS. As therapy for early-stage disease moves to further reductions in therapy, these factors take on added importance in the interpretation of current trial results and design of future studies.

    View details for DOI 10.1016/j.ijrobp.2010.07.041

    View details for PubMedID 20934280

  • Patterns of Failure in Patients with Stage I/II Bulky Mediastinal Hodgkin Lymphoma (HL) Treated with ABVD plus Radiotherapy or the Stanford V Regimen in the Randomized Phase III North American Intergroup Trial: E2496 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Advani, R., Hong, F., Gordon, L. I., Gascoyne, R. D., Wagner, H., Hoppe, R. T., Fisher, R. I., Bartlett, N. L., Kahl, B. S., Stiff, P., Cheson, B. D., Belch, A. R., Friedberg, J. W., Kassis, J., Blum, K. A., Habermann, T. M., Tuscano, J., Horning, S. J. AMER SOC HEMATOLOGY. 2011: 696–97
  • Frontline Therapy of Nodular Lymphocyte Predominant Hodgkin Lymphoma with Rituximab: The Stanford University Experience Advani, R. H., Horning, S. J., Hoppe, R. T., Daadi, S., Allen, J., Natkunam, Y., McMillan, A., Bartlett, N. L. AMER SOC HEMATOLOGY. 2011: 1154
  • Graft-Versus-Lymphoma Effect After Non-Myeloablative Allogeneic Transplant Induces Molecular Remission Assessed by High-Throughput Sequencing of T Cell Receptor in Patients with Advanced Stage Mycosis Fungoides and Sezary Syndrome Weng, W., Armstrong, R., Arai, S., Sutherland, K., Hoppe, R. T., Kim, Y. H. AMER SOC HEMATOLOGY. 2011: 1346
  • REVISITING LOW-DOSE TOTAL SKIN ELECTRON BEAM THERAPY IN MYCOSIS FUNGOIDES INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Harrison, C., Young, J., Navi, D., Riaz, N., Lingala, B., Kim, Y., Hoppe, R. 2011; 81 (4): E651-E657

    Abstract

    Total skin electron beam therapy (TSEBT) is a highly effective treatment for mycosis fungoides (MF). The standard course consists of 30 to 36 Gy delivered over an 8- to 10-week period. This regimen is time intensive and associated with significant treatment-related toxicities including erythema, desquamation, anhydrosis, alopecia, and xerosis. The aim of this study was to identify a lower dose alternative while retaining a favorable efficacy profile.One hundred two MF patients were identified who had been treated with an initial course of low-dose TSEBT (5-<30 Gy) between 1958 and 1995. Patients had a T stage classification of T2 (generalized patch/plaque, n = 51), T3 (tumor, n = 29), and T4 (erythrodermic, n = 22). Those with extracutaneous disease were excluded.Overall response (OR) rates (>50% improvement) were 90% among patients with T2 to T4 disease receiving 5 to <10 Gy (n = 19). In comparison, OR rates between the 10 to <20 Gy and 20 to <30 Gy subgroups were 98% and 97%, respectively. There was no significant difference in median progression free survival (PFS) in T2 and T3 patients when stratified by dose group, and PFS in each was comparable to that of the standard dose.OR rates associated with low-dose TSEBT in the ranges of 10 to <20 Gy and 20 to <30 Gy are comparable to that of the standard dose (≥ 30 Gy). Efficacy measures including OS, PFS, and RFS are also favorable. Given that the efficacy profile is similar between 10 and <20 Gy and 20 and <30 Gy, the utility of TSEBT within the lower dose range of 10 to <20 Gy merits further investigation, especially in the context of combined modality treatment.

    View details for DOI 10.1016/j.ijrobp.2011.01.023

    View details for Web of Science ID 000309412300060

    View details for PubMedID 21489711

  • NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Hoppe, R. T., Advani, R. H., Ai, W. Z., Ambinder, R. F., Bello, C. M., Bierman, P. J., Blum, K. A., Dabaja, B., Duron, Y., Forero, A., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Hochberg, E. P., Maloney, D. G., Mansur, D., Mauch, P. M., Metzger, M., Moore, J. O., Morgan, D., Moskowitz, C. H., Poppe, M., Pro, B., Weiss, L., Winter, J. N., Yahalom, J. 2011; 9 (9): 1020-1058
  • Clinical End Points and Response Criteria in Mycosis Fungoides and Sezary Syndrome: A Consensus Statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer JOURNAL OF CLINICAL ONCOLOGY Olsen, E. A., Whittaker, S., Kim, Y. H., Duvic, M., Prince, H. M., Lessin, S. R., Wood, G. S., Willemze, R., Demierre, M., Pimpinelli, N., Bernengo, M. G., Ortiz-Romero, P. L., Bagot, M., Estrach, T., Guitart, J., Knobler, R., Sanches, J. A., Iwatsuki, K., Sugaya, M., Dummer, R., Pittelkow, M., Hoppe, R., Parker, S., Geskin, L., Pinter-Brown, L., Girardi, M., Burg, G., Ranki, A., Vermeer, M., Horwitz, S., Heald, P., Rosen, S., Cerroni, L., Dreno, B., Vonderheid, E. C. 2011; 29 (18): 2598-2607

    Abstract

    Mycosis fungoides (MF) and Sézary syndrome (SS), the major forms of cutaneous T-cell lymphoma, have unique characteristics that distinguish them from other types of non-Hodgkin's lymphomas. Clinical trials in MF/SS have suffered from a lack of standardization in evaluation, staging, assessment, end points, and response criteria. Recently defined criteria for the diagnosis of early MF, guidelines for initial evaluation, and revised staging and classification criteria for MF and SS now offer the potential for uniform staging of patients enrolled in clinical trials for MF/SS. This article presents consensus recommendations for the general conduct of clinical trials of patients with MF/SS as well as methods for standardized assessment of potential disease manifestations in skin, lymph nodes, blood, and visceral organs, and definition of end points and response criteria. These guidelines should facilitate collaboration among investigators and collation of data from sponsor-generated or investigator-initiated clinical trials involving patients with MF or SS.

    View details for DOI 10.1200/JCO.2010.32.0630

    View details for Web of Science ID 000291684600038

    View details for PubMedID 21576639

    View details for PubMedCentralID PMC3422534

  • Treatment strategies in limited stage follicular NHL BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY Hoppe, R. T. 2011; 24 (2): 179-186

    Abstract

    Limited stage (I-II) follicular lymphoma is an uncommon entity, since most patients with this disease have generalized adenopathy (stage III) or bone marrow involvement (stage IV). Although patients who present with stage III-IV disease often are considered to be incurable, ~50% of patients with limited disease will enjoy long-term freedom-from progression, usually following treatment with radiation therapy. Relapse among these patients is uncommon after 10 years and exceedingly rare after 15 years. Radiation treatment is generally restricted to the involved nodal region(s) with modest (~5 cm.) extension proximally and distally. Radiation dose is generally 30 Gy, but may be boosted slightly (36 Gy total) in the presence of bulky disease. Randomized clinical trials have been insufficiently powered to define the value of any additional treatment beyond radiation therapy, although single arm studies suggest a benefit to the addition of chemotherapy. There have been no reported experiences with chemo-immunotherapy or radioimmunotherapy. Patients should be monitored during follow up to identify transformation to a more aggressive lymphoma.

    View details for DOI 10.1016/j.beha.2011.02.008

    View details for Web of Science ID 000292355200008

    View details for PubMedID 21658617

  • The Stanford University Experience With Conventional-Dose, Total Skin Electron-Beam Therapy in the Treatment of Generalized Patch or Plaque (T2) and Tumor (T3) Mycosis Fungoides ARCHIVES OF DERMATOLOGY Navi, D., Riaz, N., Levin, Y. S., Sullivan, N. C., Kim, Y. H., Hoppe, R. T. 2011; 147 (5): 561-567

    Abstract

    To review the Stanford University experience with total skin electron-beam therapy (TSEBT) of 30 Gy or greater as monotherapy in patients with mycosis fungoides (MF) and compare with subgroups receiving adjuvant nitrogen mustard (HN2), and further update our experience with repeated courses of TSEBT.Retrospective study.Academic referral center, multidisciplinary clinic.A total of 180 patients with MF treated from 1970 through 2007 with T2 MF (103 with generalized patch or plaque disease) or T3 MF (77 with tumor disease). Patients with extracutaneous disease were excluded.Total skin electron-beam therapy with or without adjuvant topical HN2.Clinical response rate, freedom from relapse (FFR), overall survival (OS), and progression-free survival (PFS) after TSEBT.The overall response rate (ORR) was 100%; 60% of patients achieved a complete clinical response (patients with T2 MF = 75%, those with T3 MF = 47%). The 5- and 10-year OS rates of the entire cohort were 59% and 40%, respectively. There were no significant differences in FFR (P = .30 for T2 disease; P = .50 for T3 disease), PFS (P = .10 for T2 disease; P = .40 for T3 disease), or OS (P = .30 for T2 disease; P = .50 for T3 disease) between adjuvant HN2 and TSEBT monotherapy cohorts. The ORR was 100% in patients receiving a second course of TSEBT with median FFR of 6 months.A TSEBT of 30 Gy or greater is highly effective in treating T2-T3 MF, with better outcomes in T2 disease. There was no clinical advantage to adjuvant HN2 as used in our cohort. Second courses of TSEBT are safe and efficacious and provide clinically meaningful palliation for select patients.

    View details for Web of Science ID 000290632100008

    View details for PubMedID 21576575

  • Non-Hodgkin's Lymphomas JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Zelenetz, A. D., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Bellam, N., Byrd, J. C., Czuczman, M. S., Fayad, L. E., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kelsey, C. R., Kim, Y. H., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Pro, B., Reddy, N., Sokol, L., Swinnen, L. J., Tsien, C., Vose, J. M., Wierda, W. G., Yahalom, J., Zafar, N. 2011; 9 (5): 484-560

    View details for Web of Science ID 000290292400005

    View details for PubMedID 21550968

  • Radiotherapy Planning for the Lymphomas: Expanding Roles for Biologic Imaging IMRT IGRT SBRT- ADVANCES IN THE TREATMENT PLANNING AND DELIVERY OF RADIOTHERAPY Hoppe, R. 2011; 43: 331-343

    Abstract

    Radiotherapy planning now uses advanced technologies to accurately image and assess the extent of disease for treatment. PET scanning has become established as perhaps the most important imaging study for patients with Hodgkin's disease. With respect to initial staging, FDG-PET is more sensitive overall than CT scanning. PET can detect disease at sites that do not meet size criteria by CT. Also, PET is more specific than CT alone because of the functional information that it provides. However, some disease may still escape PET imaging, and false negative results can occur. With respect to treatment response, PET has now become accepted as the most important response measure for the lymphomas. Current protocols are investigating the benefit of this information for radiotherapy planning, and even the possible elimination of radiotherapy in patients completely responding to chemotherapy. For radiotherapy planning, PET/CT should be obtained prior to and after chemotherapy; both scans give important information for the design of the radiation treatment. This chapter will review specific guidelines for planning radiotherapy based on these new imaging capabilities.

    View details for Web of Science ID 000292117400016

    View details for PubMedID 21625161

  • Principles of Radiation Techniques in Hodgkin Lymphoma HODGKIN LYMPHOMA: A COMPREHENSIVE UPDATE ON DIAGNOSTICS AND CLINICS Yahalom, J., Hoppe, R. T., Engert, A., Horning, S. J. 2011: 117–39
  • In Situ Vaccination with TLR9 Agonist Combined with Local Radiation In Mycosis Fungoides: Analysis of Phase I/II Study 52nd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Kim, Y. H., Gratzinger, D., Harrison, C., Brody, J., Czerwinski, D., Xing, L., Morales, A., Ai, W., Abdulla, F., Navi, D., Tibshirani, R. J., Advani, R., Natkunam, Y., Hoppe, R. T., Levy, R. AMER SOC HEMATOLOGY. 2010: 130–30
  • A Randomized Phase III Trial of ABVD Vs. Stanford V +/- Radiation Therapy In Locally Extensive and Advanced Stage Hodgkin's Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperatve Oncology Group (E2496) Gordon, L. I., Hong, F., Fisher, R. I., Bartlett, N. L., Connors, J. M., Gascoyne, R. D., Wagner, H., Stiff, P. J., Cheson, B. D., Gospodarowicz, M., Advani, R., Kahl, B., Friedberg, J. W., Blum, K. A., Habermann, T. M., Tuscano, J., Hoppe, R., Horning, S. J. AMER SOC HEMATOLOGY. 2010: 185
  • Randomized Phase III Trial Comparing ABVD plus Radiotherapy and the Stanford V.Regimen In Patients with Stage I/II Bulky Mediastinal Hodgkin Lymphoma: A-Subset Analysis of the US Intergroup Trial E2496 Advani, R., Hong, F., Fisher, R. I., Bartlett, N. L., Robinson, S., Gascoyne, R. D., Wagner, H., Stiff, P. J., Cheson, B. D., Stewart, D. A., Gordon, L. I., Kahl, B., Friedberg, J. W., Blum, K. A., Habermann, T. M., Tuscano, J., Hoppe, R., Horning, S. J. AMER SOC HEMATOLOGY. 2010: 185–86
  • Classical Hodgkin Lymphoma in First Complete Remission: Is There a Role for F-18 FDG PET/CT Surveillance? 23rd Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) Lagaru, A., Maeda, L. S., Lin, F. I., Hoppe, R. T., Rosenberg, S. A., Gambhir, S. S., Advani, R. H. SPRINGER. 2010: S212–S213
  • In Situ Vaccination With a TLR9 Agonist Induces Systemic Lymphoma Regression: A Phase I/II Study JOURNAL OF CLINICAL ONCOLOGY Brody, J. D., Ai, W. Z., Czerwinski, D. K., Torchia, J. A., Levy, M., Advani, R. H., Kim, Y. H., Hoppe, R. T., Knox, S. J., Shin, L. K., Wapnir, I., Tibshirani, R. J., Levy, R. 2010; 28 (28): 4324-4332

    Abstract

    Combining tumor antigens with an immunostimulant can induce the immune system to specifically eliminate cancer cells. Generally, this combination is accomplished in an ex vivo, customized manner. In a preclinical lymphoma model, intratumoral injection of a Toll-like receptor 9 (TLR9) agonist induced systemic antitumor immunity and cured large, disseminated tumors.We treated 15 patients with low-grade B-cell lymphoma using low-dose radiotherapy to a single tumor site and-at that same site-injected the C-G enriched, synthetic oligodeoxynucleotide (also referred to as CpG) TLR9 agonist PF-3512676. Clinical responses were assessed at distant, untreated tumor sites. Immune responses were evaluated by measuring T-cell activation after in vitro restimulation with autologous tumor cells.This in situ vaccination maneuver was well-tolerated with only grade 1 to 2 local or systemic reactions and no treatment-limiting adverse events. One patient had a complete clinical response, three others had partial responses, and two patients had stable but continually regressing disease for periods significantly longer than that achieved with prior therapies. Vaccination induced tumor-reactive memory CD8 T cells. Some patients' tumors were able to induce a suppressive, regulatory phenotype in autologous T cells in vitro; these patients tended to have a shorter time to disease progression. One clinically responding patient received a second course of vaccination after relapse resulting in a second, more rapid clinical response.In situ tumor vaccination with a TLR9 agonist induces systemic antilymphoma clinical responses. This maneuver is clinically feasible and does not require the production of a customized vaccine product.

    View details for DOI 10.1200/JCO.2010.28.9793

    View details for Web of Science ID 000282272700032

    View details for PubMedID 20697067

    View details for PubMedCentralID PMC2954133

  • Non-Hodgkin's Lymphomas JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Zelenetz, A. D., Abramson, J. S., Advani, R. H., Andreadis, C. B., Byrd, J. C., Czuczman, M. S., Fayad, L., Forero, A., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kaminski, M. S., Kim, Y. H., LaCasce, A. S., Mughal, T. I., Nademanee, A., Porcu, P., Press, O., Prosnitz, L., Reddy, N., Smith, M. R., Sokol, L., Swinnen, L., Vose, J. M., Wierda, W. G., Yahalom, J., Yunus, F. 2010; 8 (3): 288-334
  • Mid-treatment Metabolic Tumor Volume Predicts Progression and Death among Patients with Hodgkin's Disease 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Tseng, D., Rachakonda, L. P., Su, Z., Advani, R., Horning, S., Rosenberg, S. A., Hoppe, R. T., Quon, A., Graves, E. E., Loo, B. W., Tran, P. T. ELSEVIER SCIENCE INC. 2010: S546–S547
  • Efficacy of Abbreviated Stanford V Chemotherapy and Involved Field Radiotherapy in Early Stage Hodgkin's Disease: Mature Results of the G4 Trial. 51st Annual Meeting and Exposition of the American-Society-of-Hematology Advani, R. H., Hoppe, R. T., Baer, D. M., Mason, J., Rosenberg, S. A., Horning, S. J. AMER SOC HEMATOLOGY. 2009: 666–67
  • Role or FDG-PET/CT Surveillance for Patients with Classical Hodgkin's Disease in First Complete Response: The Stanford University Experience. 51st Annual Meeting and Exposition of the American-Society-of-Hematology Maeda, L. S., Horning, S. J., Iagaru, A. H., Lin, F. I., Hoppe, R. T., Rosenberg, S. A., Advani, R. H. AMER SOC HEMATOLOGY. 2009: 626–26
  • How I treat mycosis fungoides and Sezary syndrome BLOOD Prince, H. M., Whittaker, S., Hoppe, R. T. 2009; 114 (20): 4337-4353

    Abstract

    The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a "stage-based" approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-alpha, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used.

    View details for DOI 10.1182/blood-2009-07-202895

    View details for Web of Science ID 000271727500005

    View details for PubMedID 19696197

  • Salvage Allogeneic Hematopoietic Cell Transplantation with Fludarabine and Low-Dose Total Body Irradiation after Rejection of First Allografts 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium Gyurkocza, B., Cao, T. M., Storb, R. F., Lange, T., Leisenring, W., Franke, G. N., Sorror, M., Hoppe, R., Maloney, D. G., Negrin, R. S., Shizuru, J. A., Sandmaier, B. M. ELSEVIER SCIENCE INC. 2009: 1314–22

    Abstract

    We summarized results in 38 consecutive patients (median age=56 years) with hematologic malignancies (n=35), aplastic anemia (n=2), or renal cell carcinoma (n=1), who underwent salvage hematopoietic cell transplantation (HCT) for allograft rejection. In 14 patients, the original donors were used for salvage HCT, and, in 24 cases, different donors were used. Conditioning for salvage HCT consisted of fludarabine (Flu) and either 3 or 4 Gy total body irradiation (TBI). Sustained engraftment was achieved in 33 patients (87%). Grafts were rejected in 5 patients (13%), 4 of whom had myelofibrosis. With a median follow-up of 2 years (range: 0.3 to 7.8 years), the 2- and 4-year estimated survivals were 49% and 42%, respectively. The 2-year relapse rate and nonrelapse mortality (NRM) were 36% and 24%, respectively. The 2-year cumulative incidences of grades II-IV acute and moderate-severe chronic graft-versus-host disease (aGVHD, cGVHD) were 42% and 41%, respectively. In this cohort, TBI dose, grafts from original versus different donors, related versus unrelated donors, and HCT comorbidity scores did not have an impact on outcomes. We concluded that graft rejection after allogeneic HCT could be overcome by salvage transplantation using conditioning with Flu and low-dose TBI.

    View details for DOI 10.1016/j.bbmt.2009.06.011

    View details for Web of Science ID 000270257200012

    View details for PubMedID 19747640

    View details for PubMedCentralID PMC2757150

  • A Meta-analysis of Patients Receiving Allogeneic or Autologous Hematopoietic Stem Cell Transplant in Mycosis Fungoides and Sezary Syndrome BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Wu, P. A., Kim, Y. H., Lavori, P. W., Hoppe, R. T., Stockerl-Goldstein, K. E. 2009; 15 (8): 982-990

    Abstract

    The survival outlook in advanced mycosis fungoides (MF) is poor. Autologous and allogeneic stem cell transplants (SCT) have been shown, in small case series and case reports, to have the potential for long-term remission or to alter disease course. Allogeneic SCT is thought to have a curative potential secondary to a graft-versus-lymphoma (GVL) effect. A patient-level meta-analysis was performed to compare the outcome of allogeneic versus autologous SCT in patients with MF/Sézary syndrome (SS) using 39 cases from the literature. There were a total of 20 allogeneic and 19 autologous transplant cases. The gender, age, and stage distribution was similar between the transplant groups. The allogeneic group received significantly more systemic therapies prior to transplant (P < .0005) and had longer follow-up after transplant. Overall survival (OS) results showed a more favorable outcome of patients who received allogeneic SCT (P = .027). Event-free survival (EFS) demonstrated a more durable response in patients who received allogeneic SCT (P = .002). In the allogeneic group, the majority (70%) of patients experienced persistent graft-versus-host disease (GVHD), mostly with mild to moderate severity, and 2 of 4 deaths were related to GVHD. Meanwhile, the majority of the deaths (8 of 10) in the autologous group were because of progressive disease. These results support the belief that allogeneic SCT offers a better survival and disease-free outcome versus autologous SCT in MF/SS, likely because of a GVL effect.

    View details for DOI 10.1016/j.bbmt.2009.04.017

    View details for Web of Science ID 000268530500011

    View details for PubMedID 19589488

  • TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors BLOOD Kohrt, H. E., Turnbull, B. B., Heydari, K., Shizuru, J. A., Laport, G. G., Miklos, D. B., Johnston, L. J., Arai, S., Weng, W., Hoppe, R. T., Lavori, P. W., Blume, K. G., Negrin, R. S., Strober, S., Lowsky, R. 2009; 114 (5): 1099-1109

    Abstract

    A hematopoietic cell transplantation regimen was adapted from a preclinical model that used reduced-intensity conditioning (RIC) and protected against graft-versus-host disease (GVHD) by skewing residual host T-cell subsets to favor regulatory natural killer T cells. One hundred eleven patients with lymphoid (64) and myeloid (47) malignancies received RIC using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) followed by the infusion of granulocyte colony-stimulating factor-mobilized grafts. Included were 34 patients at least 60 years of age, 32 patients at high risk of lymphoma relapse after disease recurrence following prior autologous transplantation, and 51 patients at high risk of developing GVHD due to lack of a fully human leukocyte antigen (HLA)-matched related donor. Durable chimerism was achieved in 97% of patients. Cumulative probabilities of acute GVHD (grades II-IV) were 2 and 10% of patients receiving related and unrelated donor grafts. Nonrelapse mortality (NRM) at 1 year was less than 4%. Cumulative incidence of chronic GVHD was 27%. The 36-month probability of overall and event-free survival was 60% and 40%, respectively. Disease status at start of conditioning and the level of chimerism achieved after transplantation significantly impacted clinical outcome. The high incidence of sustained remission among patients with active disease at time of transplantation suggests retained graft-versus-tumor reactions. Active trial registration currently at clinicaltrials.gov under IDs of NCT00185640 and NCT00186615.

    View details for DOI 10.1182/blood-2009-03-211441

    View details for PubMedID 19423725

  • Cutaneous Peripheral T-Cell Lymphoma Associated With a Proliferation of B Cells AMERICAN JOURNAL OF CLINICAL PATHOLOGY Mattoch, I. W., Fulton, R., Kim, Y., Hoppe, R., Warnke, R. A., Sundram, U. N. 2009; 131 (6): 810-819

    Abstract

    Although the new World Health Organization-European Organization for Research and Treatment of Cancer classification focuses on providing uniformity in the diagnosis of cutaneous lymphomas, cutaneous peripheral T-cell lymphoma (PTL) remains a poorly defined subgroup. As follow-up to a study of systemic PTL complicated by a proliferation of B cells, we studied 16 cases of cutaneous PTL that contained morphologically atypical T cells associated with a significant infiltrate of B cells (about 20%-50%). A clonal T-cell receptor gamma chain gene rearrangement was present in all cases. In contrast, a clonal immunoglobulin heavy chain gene rearrangement was present in only 1 case. Clinical staging in 14 cases identified systemic involvement in 2. At last follow-up, both patients with systemic involvement had died of disease, and the majority of patients with primary cutaneous disease were alive (11/12). The presence of numerous atypical B cells and T cells caused diagnostic confusion in these cases. Comprehensive pathologic studies, coupled with clinical staging, are necessary for the accurate diagnosis of this unusual manifestation of cutaneous PTL.

    View details for DOI 10.1309/AJCP5W0VOCSVOBRA

    View details for Web of Science ID 000266238600010

    View details for PubMedID 19461087

  • Prognostic Factors in Primary Cutaneous Anaplastic Large Cell Lymphoma Characterization of Clinical Subset With Worse Outcome 49th Annual Meeting of the American-Society-of-Hematology Woo, D. K., Jones, C. R., Vanoli-Storz, M. N., Kohler, S., Reddy, S., Advani, R., Hoppe, R. T., Kim, Y. H. AMER MEDICAL ASSOC. 2009: 667–74

    Abstract

    To identify prognostic factors in primary cutaneous anaplastic large cell lymphoma (pcALCL), focusing on extensive limb disease (ELD), defined as initial presentation or progression to multiple skin tumors in 1 limb or contiguous body regions, and to study gene expression profiles of patients with pcALCL.Retrospective cohort study.The Stanford Comprehensive Cancer Center and dermatology ambulatory clinics.A total of 48 patients with pcALCL evaluated from 1990 through 2005.Hazard ratios (HRs) for prognostic factors for overall survival (OS) and disease-specific survival (DSS) and risk factors for progression to extracutaneous disease were identified using Cox regression. Gene expression profiles of 9 typical pcALCL and 3 ELD samples were investigated using complementary DNA microarrays.Univariate analysis demonstrated age, ELD, and progression to extracutaneous disease as significant prognostic factors for OS, whereas ELD and progression to extracutaneous disease were significant for DSS. In multivariate analysis, age (HR, 1.83; 95% confidence interval [CI], 1.02-3.26) and progression to extracutaneous disease (HR, 6.42; 95% CI, 1.39-29.68) remained significant for OS, whereas ELD (HR, 29.31; 95% CI, 1.72-500.82) and progression to extracutaneous disease (HR, 13.12; 95% CI, 1.03-167.96) remained independent prognostic factors for DSS. Presentation with T3 disease was a risk factor for progression to extracutaneous disease (HR, 10.20; 95% CI, 1.84-56.72). Microarray data revealed that patients with ELD and typical pcALCL formed distinct clusters.Patients with ELD have a more aggressive course associated with a differential gene expression profile. More aggressive treatments may be indicated for patients with ELD and those whose disease progresses to extracutaneous disease because they have poorer outcomes.

    View details for PubMedID 19528422

  • Dynamic CD8 T-cell responses to tumor-associated Epstein-Barr virus (EBV) antigens in patients with EBV-negative Hodgkin's disease 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Kohrt, H. E., Advani, R., Hoppe, R., Rosenberg, S., Horning, S., Lee, P. P. AMER SOC CLINICAL ONCOLOGY. 2009
  • Low Stage Follicular Lymphoma: Biologic and Clinical Characterization According to Nodal or Extranodal Primary Origin AMERICAN JOURNAL OF SURGICAL PATHOLOGY Weinberg, O. K., Ma, L., Seo, K., Beck, A. H., Pai, R. K., Morales, A., Kim, Y., Sundram, U., Tan, D., Horning, S. J., Hoppe, R. T., Natkunam, Y., Arber, D. A. 2009; 33 (4): 591-598

    Abstract

    Studies suggest that primary extranodal follicular lymphoma (FL) is not infrequent but it remains poorly characterized with variable histologic, molecular, and clinical outcome findings. We compared 27 extranodal FL to 44 nodal FL using morphologic, immunohistochemical, and molecular genetic techniques and evaluated the clinical outcome of these 2 similarly staged groups. Eight cases of primary cutaneous follicle center lymphoma were also studied. In comparison to nodal FL, a greater number of extranodal FL contained a diffuse growth pattern (P=0.004) and lacked CD10 expression (P=0.014). Fifty-four percent of extranodal and 42% of nodal FL cases showed evidence of t(14;18), with minor breakpoints (icr, 3'BCL2, 5'mcr) more commonly found in extranodal cases (P=0.003). Outcome data showed no significant differences in overall survival (P=0.565) and progression-free survival (P=0.627) among extranodal, nodal, and primary cutaneous follicle center lymphoma cases. Analysis of all cases by t(14;18) status indicate that the translocation-negative group is characterized by a diffuse growth pattern (P=0.043) and lower BCL2 expression (P=0.018). The t(14;18)-positive group showed significantly better overall survival (P=0.019) and disease-specific survival (P=0.006) in comparison with the t(14;18)-negative group. In low stage FL, the status of t(14;18) seems to be more predictive of outcome than origin from an extranodal versus nodal site.

    View details for Web of Science ID 000264818800014

    View details for PubMedID 19065102

  • Dynamic CD8 T-Cell Responses to Tumor-Associated Epstein-Barr Virus Antigens in Patients With Epstein-Barr Virus-Negative Hodgkin's Disease ONCOLOGY RESEARCH Kohrt, H., Johannsen, A., Hoppe, R., Horning, S. J., Rosenberg, S. A., Advani, R., Lee, P. P. 2009; 18 (5-6): 287-292

    Abstract

    In almost half of patients diagnosed with Hodgkin's disease (HD), the malignant Reed-Sternberg (RS) cells express Epstein-Barr virus (EBV) antigens. Multiple translational efforts are actively investigating antitumor immune strategies by stimulating cytotoxic T lymphocytes (CTL) against tumor-associated EBV antigens. It has previously been believed that this therapeutic strategy and presence of EBV-specific CTLs are limited to EBV-positive HD. In an effort to explore the EBV-specific immune response, here we characterize EBV-specific CTL responses to lytic and latent EBV antigens in 12 consecutive EBV carriers with EBV-negative HD. Compared to healthy donors, we detected weak, baseline EBV-specific responses to both lytic and latent antigens by IFN-gamma ELISPOT in patients with EBV-negative HD at diagnosis. Chemoradiotherapy was associated temporally with a decrease EBV-specific responses. At final follow-up (24 months), recovery of EBV-specific CTL responses was observed with robustness of lytic-specific response equivalent to healthy controls. We confirm evidence of EBV-specific CTLs in patients with EBV-negative HD and provide the first report of dynamic variance in this population during treatment. Our observation challenges prior belief that patients with HD remain immunodeficient following therapy and argues that the clinical significance of the EBV-specific immune response in EBV-negative HD should be further investigated.

    View details for DOI 10.3727/096504009X12596189659169

    View details for PubMedID 20225766

  • Indolent primary cutaneous B-cell lymphoma: Experience using systemic rituximab JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Morales, A. V., Advani, R., Horwitz, S. M., Riaz, N., Reddy, S., Hoppe, R. T., Kim, Y. H. 2008; 59 (6): 953-957

    Abstract

    Optimal treatment of indolent primary cutaneous B-cell lymphoma (CBCL), marginal zone lymphoma, and follicle center lymphoma, presenting as multiple lesions, has yet to be established. Rituximab is a chimeric monoclonal IgG1 antibody directed against the CD20 antigen of B cells. Clinical efficacy of systemic rituximab in CBCL has yet to be established.We sought to assess the efficacy of systemic rituximab in the treatment of CBCL.This was a retrospective study of 15 patients with indolent CBCL treated with intravenous rituximab (375 mg/m(2)) as a single agent. Variable maintenance regimen was used in a subset of patients. Responses were categorized as complete response, partial response, stable disease, or progressive disease. The efficacy end points included were objective response rate, time to response, time to progression, and duration of response.Ten patients with follicle center lymphoma and 5 with marginal zone lymphoma were included. The objective response rate was 87% (60% complete response, 27% partial response). All patients with follicle center lymphoma had a response with 80% achieving complete response. Of the patients with marginal zone lymphoma, 3 had a response, one stable disease, and one progressive disease. Median follow-up was 36 months. Median time to response, duration of response, and time to progression was 30 days, 24 months, and 24 months, respectively.The study was limited by the small sample size and retrospective design.This study, although small, suggests that rituximab is a reasonable first-line treatment option for indolent CBCL with multiple lesions where local treatment is not effective or desirable.

    View details for DOI 10.1016/j.jaad.2008.08.005

    View details for Web of Science ID 000261141600006

    View details for PubMedID 18817999

  • Clinicopathologic features and treatment outcomes in Woringer-Kolopp disease JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Lee, J., Viakhireva, N., Cesca, C., Lee, P., Kohler, S., Hoppe, R. I., Kim, Y. H. 2008; 59 (4): 706-712

    Abstract

    Woringer-Kolopp disease, also known as pagetoid reticulosis, is an exceedingly rare variant of mycosis fungoides. Accurate diagnosis and effective treatment is essential to prevent progression to debilitating disease. We identified 7 patients with Woringer-Kolopp disease treated at our institution. We review the major clinical and pathologic characteristics of this disease, focusing on treatment strategies and patient outcomes. All of our patients were successfully treated with skin-directed therapies including topical steroids, topical nitrogen mustard, psoralen plus ultraviolet A, narrow-band ultraviolet B, and radiation therapy. Our observations confirm that Woringer-Kolopp disease carries an excellent prognosis, and support that the most effective and appropriate treatment for recalcitrant or severe Woringer-Kolopp disease is localized radiation therapy.

    View details for DOI 10.1016/j.jaad.2008.04.018

    View details for PubMedID 18550209

  • European Organization for Research and Treatment of Cancer and International Society for Cutaneous Lymphoma consensus recommendations for the management of cutaneous B-cell lymphomas BLOOD Senff, N. J., Noordijk, E. M., Kim, Y. H., Bagot, M., Berti, E., Cerroni, L., Dummer, R., Duvic, M., Hoppe, R. T., Pimpinelli, N., Rosen, S. T., Vermeer, M. H., Whittaker, S., Willemze, R. 2008; 112 (5): 1600-1609

    Abstract

    Primary cutaneous B-cell lymphomas (CBCL) represent approximately 20% to 25% of all primary cutaneous lymphomas. With the advent of the World Health Organization-European Organization for Research and Treatment of Cancer (EORTC) Consensus Classification for Cutaneous Lymphomas in 2005, uniform terminology and classification for this rare group of neoplasms were introduced. However, staging procedures and treatment strategies still vary between different cutaneous lymphoma centers, which may be because consensus recommendations for the management of CBCL have never been published. Based on an extensive literature search and discussions within the EORTC Cutaneous Lymphoma Group and the International Society for Cutaneous Lymphomas, the present report aims to provide uniform recommendations for the management of the 3 main groups of CBCL. Because no systematic reviews or (randomized) controlled trials were available, these recommendations are mainly based on retrospective studies and small cohort studies. Despite these limitations, there was consensus among the members of the multidisciplinary expert panel that these recommendations reflect the state-of-the-art management as currently practiced in major cutaneous lymphoma centers. They may therefore contribute to uniform staging and treatment and form the basis for future clinical trials in patients with a CBCL.

    View details for DOI 10.1182/blood-2008-04-152850

    View details for Web of Science ID 000258956200013

    View details for PubMedID 18567836

  • Hodgkin disease/lymphoma. Journal of the National Comprehensive Cancer Network Hoppe, R. T., Advani, R. H., Ambinder, R. F., Bierman, P. J., Bloomfield, C. D., Blum, K., Dabaja, B., Djulbegovic, B., Forero, A., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Hudson, M. M., Kaminski, M. S., Love, G., Maloney, D. G., Mansur, D., Mauch, P. M., Moore, J. O., Schilder, R. J., Weiss, L. M., Winter, J. N., Yahalom, J., Zelenetz, A. D. 2008; 6 (6): 594-622

    View details for PubMedID 18597713

  • Clinical and immunologic responses to a novel in situ lymphoma vaccine maneuver: Results of a phase II trial of intra-tumoral CPG-[PF-3512676] 10th International Conference on Malignant Lymphoma Brody, J. D., Ai, W. Z., Czerwinski, D. K., Advani, R., Horning, S. J., Hoppe, R. T., Levy, R. OXFORD UNIV PRESS. 2008: 158–158
  • Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma MODERN PATHOLOGY Xie, X., Sundram, U., Natkunam, Y., Kohler, S., Hoppe, R. T., Kim, Y. H., Cook, J. R., Hammel, J., Swerdlow, S. H., Guitart, J., Smith, M. D., Bosler, D., Listinsky, C., Lossos, I. S., Hsi, E. D. 2008; 21 (6): 653-659

    Abstract

    The classification of primary cutaneous large B-cell lymphoma (PCLBCL) is based on standard morphology, immunohistochemistry, and clinical presentation. There are two major subtypes in the current WHO-EORTC classification: follicle center lymphoma and diffuse large B-cell lymphoma, leg-type (DLBCL-LT). The goals of this study were to examine a series of DLBCLs to determine (1) whether the immunohistochemical paradigm of germinal center B-cell and non-germinal center B-cell types of systemic DLBCL could be applied to PCLBCL; (2) whether application of the newly described germinal center B-cell marker, human germinal center-associated lymphoma (HGAL) also discriminates between these types as a further support for germinal center B-cell origin for primary cutaneous center lymphoma; and (3) whether any of these biologic markers were of prognostic significance. To this end, 32 cases of diffuse PCLBCL (22 primary cutaneous follicular center lymphomas and 10 DLBCL-LT) were classified based on the WHO-EORTC criteria and studied for expression of CD20, BCL2, BCL6, CD10, MUM-1, and HGAL by immunohistochemistry. Results were correlated with clinical features. HGAL and BCL6 expression and germinal center B-cell phenotype were associated with primary cutaneous follicular center lymphoma. The combination of HGAL and BCL6 positivity had the highest sensitivity (88%) and specificity (100%) for predicting subtype compared to either marker alone. Both HGAL and BCL6 were associated with the germinal center B-cell phenotype. The correlation of HGAL expression with the germinal center B-cell phenotype demonstrates the role of this marker in the classification of cutaneous large B-cell lymphomas. BCL6 expression was the only immunohistochemical marker associated with overall survival. Characterizing PCLBCLs with markers of B-cell maturation stage is a useful framework for studying, classifying, and clinically stratifying these lymphomas.

    View details for DOI 10.1038/modpathol.2008.30

    View details for Web of Science ID 000256112900002

    View details for PubMedID 18264083

  • Improved prognosis after histologic transformation (HT) of follicular lymphoma (FL): The Stanford experience 1960-2003 10th International Conference on Malignant Lymphoma Tan, D., Rosenberg, S. A., Lavori, P., Levy, R., Hoppe, R., Warnke, R., Advani, R., Natkuunam, Y., Yuen, A., Horning, S. J. OXFORD UNIV PRESS. 2008: 111–112
  • Attitudes and beliefs towards surviorship issues in Hodgkin's disease (HD). Results of focus group discussions with patients treated at stanford university 10th International Conference on Malignant Lymphoma Advani, R., Rosenberg, S., Talreja, N., Hoppe, R., Horning, S. OXFORD UNIV PRESS. 2008: 137–137
  • Closing the gap: A comparison of observed versus expected survival in follicular lymphoma (FL) at Stanford University from 1960-2003 Tan, D., Rosenberg, S. A., Lavori, P., Sigal, B. M., Levy, R., Hoppe, R. T., Warnke, R., Advani, R., Natkunam, Y., Plevritis, S. K., Horning, S. J. AMER SOC CLINICAL ONCOLOGY. 2008
  • Tolerance and chimerism after renal and hematopoietic-cell transplantation. New England journal of medicine Scandling, J. D., Busque, S., Dejbakhsh-Jones, S., Benike, C., Millan, M. T., Shizuru, J. A., Hoppe, R. T., Lowsky, R., Engleman, E. G., Strober, S. 2008; 358 (4): 362-368

    Abstract

    We describe a recipient of combined kidney and hematopoietic-cell transplants from an HLA-matched donor. A post-transplantation conditioning regimen of total lymphoid irradiation and antithymocyte globulin allowed engraftment of the donor's hematopoietic cells. The patient had persistent mixed chimerism, and the function of the kidney allograft has been normal for more than 28 months since discontinuation of all immunosuppressive drugs. Adverse events requiring hospitalization were limited to a 2-day episode of fever with neutropenia. The patient has had neither rejection episodes nor clinical manifestations of graft-versus-host disease.

    View details for DOI 10.1056/NEJMoa074191

    View details for PubMedID 18216356

  • Brief report: Tolerance and chimerism after renal and hematopoietic-cell transplantation NEW ENGLAND JOURNAL OF MEDICINE Scandling, J. D., Busque, S., Dejbakhsh-Jones, S., Benike, C., Millan, M. T., Shizuru, J. A., Hoppe, R. T., Lowsky, R., Engleman, E. G., Strober, S. 2008; 358 (4): 362-368

    Abstract

    We describe a recipient of combined kidney and hematopoietic-cell transplants from an HLA-matched donor. A post-transplantation conditioning regimen of total lymphoid irradiation and antithymocyte globulin allowed engraftment of the donor's hematopoietic cells. The patient had persistent mixed chimerism, and the function of the kidney allograft has been normal for more than 28 months since discontinuation of all immunosuppressive drugs. Adverse events requiring hospitalization were limited to a 2-day episode of fever with neutropenia. The patient has had neither rejection episodes nor clinical manifestations of graft-versus-host disease.

    View details for Web of Science ID 000252507900006

  • Survival in follicular lymphoma: The Stanford experience, 1960-2003. 49th Annual Meeting of the American-Society-of-Hematology Tan, D., Rosenberg, S. A., Levy, R., Lavori, P., Tibshirani, R., Hoppe, R. T., Warnke, R., Advani, R., Natkunam, Y., Yuen, A., Horning, S. J. AMER SOC HEMATOLOGY. 2007: 1005A–1005A
  • Prognostic factors in primary cutaneous anaplastic large cell lymphoma: Clinical and molecular characterization of a subset with worse outcome 49th Annual Meeting of the American-Society-of-Hematology Woo, D., Jones, C., Vanoli-Storz, M., Kohler, S., Reddy, S., Advani, R., Hoppe, R., Kim, Y. AMER SOC HEMATOLOGY. 2007: 1045A–1045A
  • Results of a prospective phase II trial of limited and extended rituximab treatment in nodular lymphocyte predominant Hodgkin's disease (NLPHD) Horning, S. J., Bartlett, N. L., Breslin, S., Advani, R. H., Hoppe, R. T., Ekstrand, B. C., Lucas, J. B. AMER SOC HEMATOLOGY. 2007: 198A
  • Stage I/II Hodgkin's disease: Comparison of outcomes of patients with bulky mediastinal disease versus other risk factors; the Stanford V experience Advani, R. H., Hoppe, R. T., Rosenberg, S. A., Horning, S. J. AMER SOC HEMATOLOGY. 2007: 685A–685A
  • Stage I/II Hodgkin's disease (HD) with bulky mediastinal disease or other risk factors (RF) the Stanford V experience 7th International Symposium on Hodgkins Lymphoma Advani, R. H., Hoppe, R. T., Rosenberg, S. A., Horning, S. J. FERRATA STORTI FOUNDATION. 2007: 27–27
  • A prospective trial of involved field radiation (IFRT) plus chemotherapy vs extended field (EFRT) radiation for favorable Hodgkin's disease (HD): Long-term follow-up and implications for current combined modality therapy 7th International Symposium on Hodgkins Lymphoma Horning, S. J., Hoppe, R. T., Advani, R. H., Breslin, S., McCormick, E., Allen, J., Hancock, S. L., Rosenberg, S. A. FERRATA STORTI FOUNDATION. 2007: 53–53
  • Hodgkin's lymphoma: The role of radiation in the modern combined strategies of treatment HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA Hoppe, R. T. 2007; 21 (5): 915-?

    Abstract

    A history of the treatment of Hodgkin's disease with radiation therapy and chemotherapy is presented. Studies are reviewed examining treatment for favorable and unfavorable presentation of stage I-II disease, stage III-IV disease, and relapsed disease. In this era of combined-modality therapy we have reached the point of near-total conquest of Hodgkin's lymphoma, but challenges remain. Directions for future research are discussed.

    View details for DOI 10.1016/j.hoc.2007.06.013

    View details for Web of Science ID 000250495500011

    View details for PubMedID 17908628

  • Impact of positive positron emission tomography on prediction of freedom from progression after Stanford V chemotherapy in Hodgkin's disease 9th International Conference on Malignant Lymphoma Advani, R., Maeda, L., Lavori, P., Quon, A., Hoppe, R., Breslin, S., Rosenberg, S. A., Horning, S. J. AMER SOC CLINICAL ONCOLOGY. 2007: 3902–7

    Abstract

    To correlate [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) status after chemotherapy, but before radiation, with outcome in patients treated with the Stanford V regimen.We analyzed retrospectively 81 patients with Hodgkin's disease who had serial [(18)F]FDG-PET scans performed at baseline and again at the completion of Stanford V chemotherapy, before planned radiotherapy. Patients with favorable stage I/II (nonbulky mediastinal disease) and those with bulky mediastinal disease or stage III/IV were scanned after 8 and 12 weeks of chemotherapy, respectively. Radiotherapy fields were determined before starting chemotherapy based on baseline computed tomography scans.After chemotherapy, six of 81 patients had residual [(18)F]FDG-PET-positive sites, all in sites for which radiotherapy was planned. Four of the six patients with positive [(18)F]FDG-PET scans after chemotherapy experienced relapse compared with just three of 75 patients with negative [(18)F]FDG-PET scans. At a median follow-up of 4 years, the freedom from progression (FFP) was 96% in postchemotherapy [(18)F]FDG-PET-negative patients versus 33% in [(18)F]FDG-PET-positive patients (P < .0003). In a bivariate Cox model, [(18)F]FDG-PET positivity after chemotherapy remained a highly significant predictor of progression-free survival even after controlling for bulky disease and International Prognostic Score more than 2.These data indicate that PET status after chemotherapy is strongly predictive of FFP with the Stanford V regimen despite the use of consolidative radiotherapy. These results have implications for the design of clinical trials adapted to functional imaging.

    View details for DOI 10.1200/JCO.2007.11.9867

    View details for PubMedID 17664458

  • TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (EORTC) BLOOD Kim, Y. H., Willemze, R., Pimpinelli, N., Whittaker, S., Olsens, E. A., Ranki, A., Dummer, R., Hoppe, R. T. 2007; 110 (2): 479-484

    Abstract

    Currently availabel staging systems for non-Hodgkin lymphomas are not useful for clinical staging classification of most primary cutaneous lymphomas. The tumor, node, metastases (TNM) system used for mycosis fungoides (MF) and Sézary syndrome (SS) is not appropriate for other primary cutaneous lymphomas. A usable, unified staging system would improve the communication about the state of disease, selection of appropriate management, standardization of enrollment/response criteria in clinical trials, and collection/analysis of prospective survival data. Toward this goal, during the recent meetings of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC), the representatives have established a consensus proposal of a TNM classification system applicable for all primary cutaneous lymphomas other than MF and SS. Due to the clinical and pathologic heterogeneity of the cutaneous lymphomas, the currently proposed TNM system is meant to be primarily an anatomic documentation of disease extent and not to be used as a prognostic guide.

    View details for DOI 10.1182/blood-2006-10-054601

    View details for Web of Science ID 000248112400008

    View details for PubMedID 17339420

  • Revised response criteria for malignant lymphoma JOURNAL OF CLINICAL ONCOLOGY Cheson, B. D., Pfistner, B., Juweid, M. E., Gascoyne, R. D., Specht, L., Horning, S. J., Coiffier, B., Fisher, R. I., Hagenbeek, A., Zucca, E., Rosen, S. T., Stroobants, S., Lister, T. A., Hoppe, R. T., Dreyling, M., Tobinai, K., Vose, J. M., Connors, J. M., Federico, M., Diehl, V. 2007; 25 (5): 579-586

    Abstract

    Standardized response criteria are needed to interpret and compare clinical trials and for approval of new therapeutic agents by regulatory agencies.The International Working Group response criteria (Cheson et al, J Clin Oncol 17:1244, 1999) were widely adopted, but required reassessment because of identified limitations and the increased use of [18F]fluorodeoxyglucose-positron emission tomography (PET), immunohistochemistry (IHC), and flow cytometry. The International Harmonization Project was convened to provide updated recommendations.New guidelines are presented incorporating PET, IHC, and flow cytometry for definitions of response in non-Hodgkin's and Hodgkin's lymphoma. Standardized definitions of end points are provided.We hope that these guidelines will be adopted widely by study groups, pharmaceutical and biotechnology companies, and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma.

    View details for DOI 10.1200/JCO.2006.09.2403

    View details for Web of Science ID 000244176000018

    View details for PubMedID 17242396

  • Screening for coronary artery disease after mediastinal irradiation for Hodgkin's disease JOURNAL OF CLINICAL ONCOLOGY Heidenreich, P. A., Schnittger, I., Strauss, H. W., Vagelos, R. H., Lee, B. K., Mariscal, C. S., Tate, D. J., Horning, S. J., Hoppe, R. T., Hancock, S. L. 2007; 25 (1): 43-49

    Abstract

    Incidental cardiac irradiation during treatment of thoracic neoplasms has increased risks for subsequent acute myocardial infarction or sudden cardiac death. Identifying patients who have a high risk for a coronary event may decrease morbidity and mortality. The objective of this study was to evaluate whether stress imaging can identify severe, unsuspected coronary stenoses in patients who had prior mediastinal irradiation for Hodgkin's disease.We enrolled 294 outpatients observed at a tertiary care cancer treatment center after mediastinal irradiation doses 35 Gy for Hodgkin's disease who had no known ischemic cardiac disease. Patients underwent stress echocardiography and radionuclide perfusion imaging at one stress session. Coronary angiography was performed at the discretion of the physician.Among the 294 participants, 63 (21.4%) had abnormal ventricular images at rest, suggesting prior myocardial injury. During stress testing, 42 patients (14%) developed perfusion defects (n = 26), impaired wall motion (n = 8), or both abnormalities (n = 8). Coronary angiography showed stenosis 50% in 22 patients (55%), less than 50% in nine patients (22.5%), and no stenosis in nine patients (22.5%). Screening led to bypass graft surgery in seven patients. Twenty-three patients developed coronary events during a median of 6.5 years of follow-up, with 10 acute myocardial infarctions (two fatal).Stress-induced signs of ischemia and significant coronary artery disease are highly prevalent after mediastinal irradiation in young patients. Stress testing identifies asymptomatic individuals at high risk for acute myocardial infarction or sudden cardiac death.

    View details for DOI 10.1200/JCO.2006.07.0805

    View details for Web of Science ID 000243725900009

    View details for PubMedID 17194904

  • Second lymphomas and other malignant neoplasms in patients with mycosis fungoides and Sezary syndrome - Evidence from population-based and clinical cohorts ARCHIVES OF DERMATOLOGY Huang, K. P., Weinstock, M. A., Clarke, C. A., McMillan, A., Hoppe, R. T., Kim, Y. H. 2007; 143 (1): 45-50

    Abstract

    To assess risks for developing second malignancies in patients with mycosis fungoides or Sézary syndrome.Retrospective study of 2 cohorts.Nine population-based US cancer registries that constitute the Surveillance, Epidemiology, and End Results Program (SEER-9), and Stanford University referral center cohort of patients with cutaneous lymphoma. Patients with mycosis fungoides or Sézary syndrome from the SEER-9 registry diagnosed and followed up from 1984 through 2001 and from the Stanford University cohort diagnosed and followed up from 1973 through 2001.Relative risk was estimated using the standardized incidence ratio (SIR). The expected cancer incidence for both cohorts was calculated using age-, sex-, race-, and calendar year-specific SEER-9 incidence rates for the general population. Nonmelanoma skin cancers were excluded because these cancers are not routinely reported by the SEER database.In the SEER-9 cohort (n = 1798), there were 197 second instances of cancer (SIR = 1.32; 95% confidence interval [CI], 1.15-1.52) at all sites. Significantly elevated risk (P<.01) was observed for Hodgkin disease (6 cases; SIR = 17.14; 95% CI, 6.25-37.26) and non-Hodgkin lymphoma (27 cases; SIR = 5.08; 95% CI, 3.34-7.38). Elevated risk (P<.05) was also observed for melanoma (10 cases; SIR = 2.60; 95% CI, 1.25-4.79), and urinary cancer (21 cases; SIR = 1.74; 95% CI, 1.08-2.66). In the Stanford University cohort (n = 429), there were 37 second instances of cancer (SIR = 1.04; 95% CI, 0.76-1.44). Elevated risk (P<.01) was observed for Hodgkin disease (3 cases; SIR = 27.27; 95% CI, 5.35-77.54). Elevated risk (P<.05) was also observed for biliary cancer (2 cases; SIR = 11.76; 95% CI, 1.51-42.02).Updated SEER (population based) and Stanford (clinic based) data confirm the generalizability of earlier findings of increased risk of lymphoma in patients with mycosis fungoides or Sézary syndrome.

    View details for Web of Science ID 000243509100006

    View details for PubMedID 17224541

  • Second malignancy risk associated with treatment of Hodgkin's lymphoma: meta-analysis of the randomised trials ANNALS OF ONCOLOGY Franklin, J., Pluetschow, A., Paus, M., Specht, L., Anselmo, A., Aviles, A., Biti, G., Bogatyreva, T., Bonadonna, G., Brillant, C., Cavalieri, E., Diehl, V., Eghbali, H., Ferme, C., Henry-Amar, M., Hoppe, R., Howard, S., Meyer, R., Niedzwiecki, D., Pavlovsky, S., Radford, J., Raemaekers, J., Ryder, D., Schiller, P., Shakhtarina, S., Valagussa, P., Wilimas, J., Yahalom, J. 2006; 17 (12): 1749-1760

    Abstract

    Despite several investigations, second malignancy risks (SMR) following radiotherapy alone (RT), chemotherapy alone (CT) and combined chemoradiotherapy (CRT) for Hodgkin's lymphoma (HL) remain controversial.We sought individual patient data from randomised trials comparing RT versus CRT, CT versus CRT, RT versus CT or involved-field (IF) versus extended-field (EF) RT for untreated HL. Overall SMR (including effects of salvage treatment) were compared using Peto's method.Data for between 53% and 69% of patients were obtained for the four comparisons. (i) RT versus CRT (15 trials, 3343 patients): SMR were lower with CRT than with RT as initial treatment (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.62-0.98 and P = 0.03). (ii) CT versus CRT (16 trials, 2861 patients): SMR were marginally higher with CRT than with CT as initial treatment (OR = 1.38, CI 1.00-1.89 and P = 0.05). (iii) IF-RT versus EF-RT (19 trials, 3221 patients): no significant difference in SMR (P = 0.28) although more breast cancers occurred with EF-RT (P = 0.04 and OR = 3.25).Administration of CT in addition to RT as initial therapy for HL decreases overall SMR by reducing relapse and need for salvage therapy. Administration of RT additional to CT marginally increases overall SMR in advanced stages. Breast cancer risk (but not SMR in general) was substantially higher after EF-RT. Caution is needed in applying these findings to current therapies.

    View details for DOI 10.1093/annonc/mdl302

    View details for Web of Science ID 000242715000005

    View details for PubMedID 16984979

  • Incidence of secondary leukemia/myelodysplasia (AML/MDS) in Hodgkin's disease (HD) with three generations of therapy at Stanford University. 42nd Annual Meeting of the American-Society-of-Clinical-Oncology Advani, R. H., Hoppe, R. T., Rosenberg, S. A., Horning, S. J. AMER SOC CLINICAL ONCOLOGY. 2006: 426S–426S
  • Staging accuracy in mycosis fungoides and Sezary syndrome using integrated positron emission tomography and computed tomography 65th Annual Meeting of the Society-for-Investigative-Dermatology Tsai, E. Y., Taur, A., Espinosa, L., Quon, A., Johnson, D., Dick, S., Chow, S., Advani, R., Warnke, R., Kohler, S., Hoppe, R. T., Kim, Y. H. AMER MEDICAL ASSOC. 2006: 577–84

    Abstract

    To evaluate the usefulness of integrated positron emission tomography and computed tomography (PET/CT) in staging mycosis fungoides (MF) and Sézary syndrome and to correlate PET/CT data with histopathologic diagnosis of lymph nodes (LNs).A single-center, prospective cohort analysis.Academic referral center for cutaneous lymphoma.Thirteen patients with MF and SS at risk for secondary LN involvement. Interventions Patients were clinically evaluated based on general physical examination, total body skin examination, and laboratory screening. They underwent integrated PET/CT followed by excisional biopsy of LNs.We used PET/CT to assess LN size and metabolic activity. Enlarged LNs were defined as axillary or inguinal LNs with a short axis 1.5 cm or larger; or cervical LN, with a short axis 1.0 cm or larger. We classified LN pathologic results according to National Cancer Institute (LN1-4) and World Health Organization (WHO 1-3) criteria. We quantified PET activity using standardized uptake value (SUV) and correlated with LN grade.Based on CT size criteria alone, only 5 patients had enlarged LNs, whereas PET revealed hypermetabolic LNs in all 13 patients. Six patients had LN1-3, and 7 had effacement of LN architecture by lymphoma cells (LN4). Of the 7 patients with LN4 nodes, 4 had SS, and 3 had tumorous MF. Two patients with LN4 nodes had inguinal LNs smaller than 1.5 cm and would have been assigned an N0 classification without the use of integrated PET/CT. Correlation of SUV with LN grade revealed that LN1-3 nodes were associated with a mean SUV of 2.7 (median SUV, 2.2; range, 2.0-4.7) and LN4 nodes were associated with a mean SUV of 5.4 (median SUV, 3.9; range, 2.1-11.8). Patients with large cell transformation had the highest SUVs.For staging MF and SS, PET/CT was more sensitive in detecting LN involved by lymphoma compared with CT data alone and thus may provide more accurate staging and prognostic information. The intensity of PET activity correlated with histologic LN grade.

    View details for PubMedID 16702495

  • The Stanford experience with utilizing the new WHO classification of cutaneous lymphomas for cutaneous B cell lymphoma 67th Annual Meeting of the Society-for-Investigative-Dermatology Reddy, S., Kohler, S., Horwitz, S., Sutherland, K., Hoppe, R. T., Kim, Y. H. NATURE PUBLISHING GROUP. 2006: 44–44
  • Assessment of favorable (F) versus unfavorable (U) early stage Hodgkin's disease (HD); the Stanford V plus radiotherapy (RT) experience. 47th Annual Meeting of the American-Society-of-Hematology Advani, R., Maeda, L., Hoppe, R. T., Breslin, S., Rosenberg, S. A., Baer, D., Mason, J., Horning, S. J. AMER SOC HEMATOLOGY. 2005: 548A–548A
  • Bexarotene is highly active in the treatment of subcutaneous Panniculitis-like T-cell lymphoma. 47th Annual Meeting of the American-Society-of-Hematology Molina, A. M., Advani, R., Reddy, S., Hoppe, R., Friedberg, J. W., Sadan, S., Myskowski, P., Kim, Y. H., Horwitz, S. M. AMER SOC HEMATOLOGY. 2005: 934A–934A
  • Protective conditioning for acute graft-versus-host disease NEW ENGLAND JOURNAL OF MEDICINE Lowsky, R., Takahashi, T., Liu, Y. P., Dejbakhsh-Jones, S., GRUMET, F. C., Shizuru, J. A., Laport, G. G., Stockerl-Goldstein, K. E., JOHNSTON, L. J., Hoppe, R. T., Bloch, D. A., Blume, K. G., Negrin, R. S., Strober, S. 2005; 353 (13): 1321-1331

    Abstract

    Conditioning with total lymphoid irradiation plus antithymocyte serum protects mice against acute graft-versus-host disease (GVHD) after hematopoietic-cell transplantation. We tested this strategy in humans.Thirty-seven patients with lymphoid malignant diseases or acute leukemia underwent an experimental conditioning regimen with 10 doses of total lymphoid irradiation (80 cGy each) plus antithymocyte globulin, followed by an infusion of HLA-matched peripheral-blood mononuclear cells from related or unrelated donors who received granulocyte colony-stimulating factor.Of the 37 transplant recipients, only 2 had acute GVHD after hematopoietic-cell transplantation. Potent antitumor effects in patients with lymphoid malignant diseases were shown by the change from partial to complete remission. In the transplant recipients who underwent conditioning with total lymphoid irradiation and antithymocyte globulin, the fraction of donor CD4+ T cells that produced interleukin-4 after in vitro stimulation increased by a factor of five, and the proliferative response to alloantigens in vitro was reduced, as compared with normal control subjects and control subjects who underwent conditioning with a single dose of total-body irradiation (200 cGy).A regimen of total lymphoid irradiation plus antithymocyte globulin decreases the incidence of acute GVHD and allows graft antitumor activity in patients with lymphoid malignant diseases or acute leukemia treated with hematopoietic-cell transplantation.

    View details for PubMedID 16192477

  • Report from the Rockefellar Foundation Sponsored International Workshop on reducing mortality and improving quality of life in long-term survivors of Hodgkin's disease: July 9-16, 2003, Bellagio, Italy 6th International Symposium on Hodgkins Disease Mauch, P., Ng, A., Aleman, B., Carde, P., Constine, L., Diehl, V., Dinshaw, K., Gospodarowicz, M., Hancock, S., Hodgson, D., Hoppe, R., Liang, R., Loeffler, M., Specht, L., Travis, L. B., Wirth, A., Yahalom, J. WILEY-BLACKWELL. 2005: 68–76

    Abstract

    A workshop, sponsored by the Rockefellar Foundation, was held between 9 to 16 July, 2003 to devise strategies to reduce mortality and improve quality of life of long-term survivors of Hodgkin's disease. Participants were selected for their clinical and research background on late effects after Hodgkin's disease therapy. Experts from both developed and developing nations were represented in the workshop, and efforts were made to ensure that the proposed strategies would be globally applicable whenever possible. The types of late complications, magnitude of the problem, contributing risk factors, methodology to assess the risk, and challenges faced by developing countries were presented. The main areas of late effects of Hodgkin's disease discussed were as follows: second malignancy, cardiac disease, infection, pulmonary dysfunction, endocrine abnormalities, and quality of life. This report summarizes the findings of the workshop, recommendations, and proposed research priorities in each of the above areas.

    View details for Web of Science ID 000229591400012

    View details for PubMedID 16007872

  • The John Ultmann lecture - the role of radiation therapy in the treatment of Hodgkin's disease: past, present, and future EUROPEAN JOURNAL OF HAEMATOLOGY Hoppe, R. T. 2005; 75: 14–20

    Abstract

    Radiation therapy has been used in the treatment of Hodgkin's disease for more than a century. At first it was demonstrated to provide significant palliation. As advances in technology permitted a more controlled delivery of radiation to defined regions, long lasting responses of disease were demonstrated. Beginning in the mid-1960s, Vera Peters and Henry Kaplan demonstrated the curative potential of high dose extended field irradiation in the treatment of stage I-II Hodgkin's disease. As effective programs of chemotherapy evolved, combined modality therapy with intensive chemotherapy and extensive radiation was applied for patients with early stage disease, resulting in significant morbidity and some mortality. More recently, combined modality programs of brief chemotherapy and limited radiation have been extremely successful in managing patients with stage I-II disease. In addition to its utility in early disease, radiation therapy is an integral component of treatment programs for patients with large mediastinal adenopathy. It has also proved useful in patients with stage III-IV who achieve only a partial response to chemotherapy and may also have a role to play as a component of high-dose therapy hematopoietic stem cell transplant programs. Radiation therapy remains the most effective single agent for the treatment of Hodgkin's disease.

    View details for DOI 10.1111/j.1600-0609.2005.00449.x

    View details for Web of Science ID 000229591400003

    View details for PubMedID 16007863

  • PET status after Stanford V chemotherapy predicts outcome in Hodgkins disease 9th International Conference on Malignant Lymphoma Advani, R., Maeda, L., Lavori, P., Hoppe, R., Breslin, S., Rosenberg, S., Horning, S. OXFORD UNIV PRESS. 2005: 121–121
  • A technique of bone marrow collection from vertebral bodies of cynomolgus macaques for transplant studies JOURNAL OF SURGICAL RESEARCH Flores, M. G., Holm, B., Larson, M. J., Lau, M. K., Si, M. S., Lowsky, R., Rousvoal, G., GRUMET, F. C., Strober, S., Hoppe, R., Reitz, B. A., Borie, D. C. 2005; 124 (2): 280-288

    Abstract

    Strategies to induce donor-specific allograft tolerance are best tested in preclinical models developed in nonhuman primates (NHPs). Most protocols prepare the recipient by infusing hematopoietic cells from the donor. We report here a procedure to isolate and characterize large numbers of bone marrow cells (BMCs) from cynomolgus monkeys (cynos) that can then successfully be transplanted into conditioned recipients.Vertebral columns of five cynos were excised en bloc and separated into individual vertebrae. The cancelous bone was extracted with a core puncher, fractionated, filtered, centrifuged, and resuspended in transplantation media before being analyzed by flow cytometry. In two instances, the collected BMCs were reinfused into allogeneic recipients preconditioned with a nonmyeloablative regimen. Chimerism was monitored using short-tandem repeat analysis.The mean total BMCs yield was 25.5 x 10(9) (range of 4.00 x 10(9) to 59 x 10(9)) with mean cell viability of 93.4% (range: 90-96%). CD34+ cells and CD3+ cells averaged 0.34 and 3.91% of total BMCs, respectively. This resulted in absolute cell number yields of 1.02 x 10(8) and 1.15 x 10(9) for CD34+ and CD3+ cells, respectively. Graft-versus-host disease was absent in both bone marrow infused animals, and a maximum level of chimerism of 18% was detected at 3 weeks after BMCs infusion.We present here the first detailed report of a procedure to retrieve and characterize large numbers of BMCs from vertebral bodies of cynos and demonstrate that cells collected with this technique have the capability of engrafting in allogenic recipients.

    View details for DOI 10.1016/j.jss.2004.09.018

    View details for Web of Science ID 000228275800018

    View details for PubMedID 15820259

  • Expression of the bcl-6 and MUM1/IRF4 proteins correlate with overall and disease-specific survival in patients with primary cutaneous large B-cell lymphoma: a tissue microarray study JOURNAL OF CUTANEOUS PATHOLOGY Sundram, U., Kim, Y., Mraz-Gernhard, S., Hoppe, R., Natkunam, Y., Kohler, S. 2005; 32 (3): 227-234

    Abstract

    Systemic B-cell lymphomas have been studied using microarrays, which has led to a better understanding of their molecular characteristics. Initial microarray studies of these lymphomas have implicated several genes as important predictors of outcome. In this study, we used a tissue microarray (TMA) to characterize primary cutaneous large B-cell lymphomas (PCLBCL).We studied 14 patients for whom clinical follow up was available, including four patients whose lesions were limited to the leg on presentation. Immunohistochemical staining with CD20, CD44, CD21, CD5, CD10, bcl-2, bcl-6, Ki67, p53, and multiple myeloma 1 (MUM1) was examined.Our results identify two subgroups of lymphomas. The first group showed staining with bcl-6 and had an overall survival of 176 months (p = 0.003). The majority of this group was negative for MUM1. The second group lacked staining with bcl-6 and had an overall survival of 26 months, with a majority of these cases staining with MUM1. Three of four patients with PCLBCL of the leg showed no staining with bcl-6.Our study demonstrates the utility of TMAs in the analysis of PCLBCL and that expression of bcl-6 and MUM1 correlates with survival.

    View details for Web of Science ID 000226857100005

    View details for PubMedID 15701085

  • Efficacy and late effects of Stanford V chemotherapy and radiotherapy in untreated Hodgkin's disease: Mature data in early and advanced stage patients. 46th Annual Meeting of the American-Society-of-Hematology Horning, S. J., Hoppe, R. T., Advani, R., Warnke, R., Baer, D., Mason, J., Rosenberg, S. A. AMER SOC HEMATOLOGY. 2004: 92A–92A
  • Primary cutaneous CD30+ anaplastic large cell lymphoma: Analysis of the Stanford series reveals two clinical subsets of patients. 46th Annual Meeting of the American-Society-of-Hematology Reddy, S. A., Liu, H., Kohler, S., Hoppe, R. T., Kim, Y. H. AMER SOC HEMATOLOGY. 2004: 226B–226B
  • Marked improvement in staging accuracy in mycosis fungoides/Sezary syndrome using integrated positron emission tomography and computed tomography (PET/CT) Tsai, E. Y., Taur, A., Espinosa, L., Quon, A., Dick, S. E., Chow, S., Advani, R., Warnke, R. A., Kohler, S., Hoppe, R. T., Kim, Y. H. AMER SOC HEMATOLOGY. 2004: 854A–855A
  • Short tandem repeat analysis to monitor chimerism in Macaca fascicularis AMERICAN JOURNAL OF TRANSPLANTATION Lau, M., Vayntrub, T., GRUMET, F. C., Lowsky, R., Strober, S., Hoppe, R., Larson, M., Holm, B., Reitz, B., Borie, D. 2004; 4 (9): 1543-1548

    Abstract

    Chimerism assessment following bone marrow transplantation (BMT) in cynomolgus monkeys (cynos) has been hampered by the lack of good engraftment markers. In human BMT, such markers have been provided by short tandem repeat (STR) loci. We tested the idea that techniques effective for detecting human STR could be readily adapted to cynos. Genomic DNA was extracted from cyno unseparated blood or peripheral cell subsets. With only slight modifications, reagents for detecting human STR alleles were used to amplify and detect cyno STRs and to quantitate allelic mixtures on an automated sequencer. Of the 15 STR loci tested, only CSF1PO, D18S51, and FGA successfully amplified, with seven, seven and two alleles, respectively. CSF1PO and D18S51 heterozygosity (80% and 55%, respectively) allowed use of these two loci for chimerism quantitation after BMT. The successful adaptation of human STR reagents to monitor chimerism in transplanted cynos will facilitate the use of this species in preclinical tolerance studies.

    View details for DOI 10.1111/j.1600-6143.2004.00529.x

    View details for Web of Science ID 000223283900021

    View details for PubMedID 15307845

  • Clinical and pathological features of posttransplantation lymphoproliferative disorders presenting with skin involvement in 4 patients ARCHIVES OF DERMATOLOGY Beynet, D. P., Wee, S. A., Horwitz, S. S., Kohler, S., Horning, S., Hoppe, R., Kim, Y. H. 2004; 140 (9): 1140-1146

    Abstract

    Posttransplantation lymphoproliferative disorders (PTLDs) are lymphoid proliferations that can develop in recipients of solid organ or allogeneic bone marrow transplants. They are clinically and pathologically heterogeneous and range from polyclonal hyperplastic lesions to malignant lymphomas. Although extranodal involvement in PTLD is common, cutaneous presentation is rare, with only 19 cases reported previously.We describe 4 patients with cutaneous presentations of PTLD. All patients had relatively late-onset PTLD (>1 year after transplantation) with a median of 8 years from organ allograft to tumor diagnosis. The extent, number, and anatomic location of skin lesions varied from a localized patch to widespread nodules. None of the patients exhibited systemic symptoms at the time of PTLD diagnosis. Pathological findings ranged from plasmacytic hyperplasia to monomorphic PTLD. In situ hybridization detected Epstein-Barr virus messenger RNA in all 3 cases with evaluable tissue. All patients underwent reduction in immunosuppressive therapy and received other individualized treatments. Median follow-up was 2.5 years. At the most recent follow-up, 3 patients were in complete remission and 1 had residual disease.In this study, PTLD lesions presenting in the skin responded to therapy. Despite their relatively late occurrence after transplantation, most of these cases were positive for Epstein-Barr virus. As observed with other cutaneous lymphomas, the PTLDs with predominant skin involvement had a relatively favorable outcome.

    View details for Web of Science ID 000223835000014

    View details for PubMedID 15381556

  • Extranodal nonorbital indolent lymphomas of the head and neck: Relationship between tumor control and radiotherapy 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) MacDermed, D., Thurber, L., George, T. I., Hoppe, R. T., Le, Q. T. ELSEVIER SCIENCE INC. 2004: 788–95

    Abstract

    To review our experience managing extranodal nonorbital indolent lymphomas of the head and neck.A retrospective review was made of 40 patients with indolent lymphomas of the head and neck evaluated at Stanford. The tumor head-and-neck location was Waldeyer's ring, 14; salivary glands, 16; thyroid, 4; and other sites, 6. Twenty-five were Stage I-IIE. Pathology was re-reviewed in 37. The most common histologies were marginal zone lymphoma and follicular grade 2. Patients received combinations of surgery, chemotherapy, and radiotherapy. Local therapy included surgery alone in 6 patients, radiotherapy alone in 7, and surgery plus radiotherapy in 12. Median follow-up was 70.5 months.Freedom from local progression was 86%, and freedom from progression was 61% at 5 years. Patients with radiotherapy had significantly better freedom from local progression (5-year, 100% vs. 72% for patients without radiotherapy, p = 0.006) and freedom from progression (5-year, 90% vs. 34% for patients without radiotherapy, p = 0.001). Improvement in freedom from progression with radiotherapy was statistically significant for Stage I-II patients (88% vs. 50%, p = 0.02) and of borderline significance in Stage III-IV patients (100% vs. 23%, p = 0.07). Overall survival at 10 years was 70%. Multivariate analysis revealed that significant prognostic factors for survival were tumor site (favoring salivary and thyroid, p = 0.02) and age (favoring younger, p = 0.04).Survival is excellent in patients with indolent lymphomas of the head and neck. Patients with salivary and thyroid primary tumors had better survival compared with others. Early use of radiotherapy resulted in significantly higher rates of freedom from progression and freedom from local progression in early-stage patients.

    View details for DOI 10.1016/j.ijrobp.2003.11.007

    View details for PubMedID 15183482

  • CD30(+) cutaneous lymphoproliferative disorders: The Stanford experience in lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Liu, H. L., Hoppe, R. T., Kohler, S., Harvell, J. D., Reddy, S., Kim, Y. H. 2003; 49 (6): 1049-1058

    Abstract

    CD30+ cutaneous lymphoproliferative disorders (CLPDs) include lymphomatoid papulosis, borderline cases of CD30+CLPDs, and primary cutaneous anaplastic large cell lymphoma (PCALCL). Prior studies have shown CD30+CLPDs have an excellent prognosis.We sought to present the single-center experience of Stanford University, Stanford, Calif, in the management of CD30+CLPDs.A retrospective cohort analysis of 56 patients with CD30+CLPDs treated at our institution was performed.No patients with lymphomatoid papulosis died of disease, and overall survival was 92% at 5 and 10 years. Disease-specific survivals at 5 and 10 years for PCALCL were 85%. Disease-specific survival at 5 years for localized versus generalized PCALCL was 91% versus 50% (P =.31). PCALCL was highly responsive to treatment, but the relapse rate was 42%. In all, 3 patients progressed to extracutaneous stage of disease. No clinical or histologic factors analyzed were predictive of worse outcome in lymphomatoid papulosis and PCALCL.Similar to prior reports from multicenter European groups, the single-center experience at our institution demonstrates CD30+CLPDs have an overall excellent prognosis; however, cases of PCALCL with poor outcome do exist.

    View details for DOI 10.1016/S0190-9622(03)02484-8

    View details for Web of Science ID 000186784800009

    View details for PubMedID 14639383

  • Long-term outcome of 525 patients with mycosis fungoides and Sezary syndrome - Clinical prognostic factors and risk for disease progression 63rd Annual Meeting of the Society-for-Investigative-Dermatology Kim, Y. H., Liu, H. L., Mraz-Gernhard, S., Varghese, A., Hoppe, R. T. AMER MEDICAL ASSOC. 2003: 857–66

    Abstract

    To study and update the clinical characteristics and long-term outcome of our patients with mycosis fungoides (MF) and Sézary syndrome (SS), and to identify important clinical factors predictive of survival and disease progression.A single-center, retrospective cohort analysis.Academic referral center for cutaneous lymphoma.Five hundred twenty-five patients with MF and SS evaluated and managed at Stanford University Cutaneous Lymphoma Clinic, Stanford, Calif, from 1958 through 1999.We calculated long-term actuarial overall and disease-specific survivals and disease progression by the Kaplan-Meier method, and relative risk (RR) for survival calculated from expected survivals in control populations.The majority of our patients presented with T1 (30%) or T2 (37%) disease; 18% presented with T3 and 15% with T4 skin involvement. Forty-three percent of deaths were attributable to MF, primarily in patients with T3 or T4 disease. The patients with a more advanced T classification and clinical stage had a worse survival outcome. Except for patients with T1 or stage IA disease, the RR for death is greater in patients with MF than in a control population (RR, 2.2 in stage IB/IIA disease, 3.9 in stage IIB/III disease, and 12.8 in stage IV disease). Despite similar overall survival in patients with stage IB or IIA disease, their disease-specific survivals were significantly different (P =.006). The most significant clinical prognostic factors in the univariate analysis were patient age, TNM and B classifications, overall clinical stage groupings, and the presence or absence of extracutaneous disease. In the multivariate analysis, patient age, T classification, and the presence of extracutaneous disease were the most important independent factors. The risk for disease progression to a more advanced TNM or B classification, worse clinical stage, or death due to MF correlated with the severity of the initial T classification. The risk for development of extracutaneous disease also correlated with T classification; none of these patients had T1 disease when their extracutaneous disease was detected.Patients with MF and SS have varying risks for disease progression or death. The most important clinical predictive factors for survival include patient age, T classification, and the presence of extracutaneous disease. The significant disease-specific survival differences between different clinical stages validate the usefulness of the present MF clinical staging system of the National Cancer Institute.

    View details for Web of Science ID 000184104500003

    View details for PubMedID 12873880

  • Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial BLOOD Ekstrand, B. C., Lucas, J. B., Horwitz, S. M., Fan, Z., Breslin, S., Hoppe, R. T., Natkunam, Y., Bartlett, N. L., Horning, S. J. 2003; 101 (11): 4285-4289

    Abstract

    Lymphocyte-predominant Hodgkin disease (LPHD) is a unique clinical entity characterized by indolent nodal disease that tends to relapse after standard radiotherapy or chemotherapy. The malignant cells of LPHD are CD20+ and therefore rituximab may have activity with fewer late effects than standard therapy. In this phase 2 trial, 22 patients with CD20+ LPHD received 4 weekly doses of rituximab at 375 mg/m2. Ten patients had previously been treated for Hodgkin disease, while 12 patients had untreated disease. All 22 patients responded to rituximab (overall response rate, 100%) with complete response (CR) in 9 (41%), unconfirmed complete response in 1 (5%), and partial response in 12 (54%). Acute treatment-related adverse events were minimal. With a median follow-up of 13 months, 9 patients had relapsed, and estimated median freedom from progression was 10.2 months. Progressive disease was biopsied in 5 patients: 3 had recurrent LPHD, while 2 patients had transformation to large-cell non-Hodgkin lymphoma (LCL). All 3 patients with recurrent LPHD were retreated with rituximab, with a second CR seen in 1 patient and stable disease in 2. Rituximab induced prompt tumor reduction in each of 22 LPHD patients with minimal acute toxicity; however, based on the relatively short response duration seen in our trial and the concerns about transformation, rituximab should be considered investigational treatment for LPHD. Further clinical trials are warranted to determine the optimal dosing schedule of rituximab, the potential for combination treatment, and the possible relationship of rituximab treatment to the development of LCL.

    View details for DOI 10.1182/blood-2002-08-2644

    View details for Web of Science ID 000183072800018

    View details for PubMedID 12586628

  • Gene expression profiles of cutaneous B cell lymphoma JOURNAL OF INVESTIGATIVE DERMATOLOGY Storz, M. N., van de Rijn, M., Kim, Y. H., Mraz-Gernhard, S., Hoppe, R. T., Kohler, S. 2003; 120 (5): 865-870

    Abstract

    We studied gene expression profiles of 17 cutaneous B cell lymphomas that were collected with 4-6 mm skin punch biopsies. We also included tissue from two cases of mycosis fungoides, three normal skin biopsies, and three tonsils to create a framework for further interpretation. A hierarchical cluster algorithm was applied for data analysis. Our results indicate that small amounts of skin tissue can be used successfully to perform microarray analysis and result in distinct gene expression patterns. Duplicate specimens clustered together demonstrating a reproducible technique. Within the cutaneous B cell lymphoma specimens two specific B cell differentiation stage signatures of germinal center B cells and plasma cells could be identified. Primary cutaneous follicular and primary cutaneous diffuse large B cell lymphomas had a germinal center B cell signature, whereas a subset of marginal zone lymphomas demonstrated a plasma cell signature. Primary and secondary follicular B cell lymphoma of the skin were closely related, despite previously reported genetic and phenotypic differences. In contrast primary and secondary cutaneous diffuse large B cell lymphoma were less related to each other. This pilot study allows a first glance into the complex and unique microenvironment of B cell lymphomas of the skin and provides a basis for future studies, which may lead to the identification of potential histologic and prognostic markers as well as therapeutic targets.

    View details for PubMedID 12713594

  • Topical nitrogen mustard in the management of mycosis fungoides - Update of the Stanford experience ARCHIVES OF DERMATOLOGY Kim, Y. H., Martinez, G., Varghese, A., Hoppe, R. T. 2003; 139 (2): 165-173

    Abstract

    To evaluate and update the response and survival outcomes and toxic effects in patients treated with topical nitrogen mustard (mechlorethamine hydrochloride) as primary therapy.A single-center, retrospective cohort analysis.Academic referral center for cutaneous lymphoma.A total of 203 patients with mycosis fungoides (clinical stages I-III) treated with topical nitrogen mustard as initial therapy.Long-term actuarial survival, freedom-from-relapse, and freedom-from-progression results as calculated by the Kaplan-Meier method.The overall response rate for the 203 patients was 83%, with a complete response rate of 50%. The median time to achieve complete response was 12 months (T1, 10 months; T2, 19 months), and the median time to relapse was 12 months. The duration of complete response increased with longer maintenance therapy; however, after completion of therapy, the response duration or relapse rate was similar regardless of maintenance regimen. Patients with T1 disease had better response and survival outcomes than those with T2 disease, with overall and complete response rates in T1 of 93% and 65%, respectively, and in T2, 72% and 34%, respectively. A similar clinical response was seen for patients with stage IIA vs IB. Sixty-eight percent of 203 patients received only topical nitrogen mustard therapy throughout their follow-up course, including most of the patients who achieved an initial complete response. The clinical response to topical nitrogen mustard as salvage therapy was similar to initial response rates. The efficacy results were similar in patients treated with aqueous vs ointment preparations. Freedom-from-progression rates in T1 disease (no progression to higher T classification or worse clinical stage) at 5 and 10 years were 92% and 85%, respectively, and in T2, 83% at 5 and 10 years. Fewer than 10% of patients experienced contact hypersensitivity reactions when topical nitrogen mustard was used as an ointment preparation. Only 8 patients (4%) developed secondary cutaneous malignancy, none attributable to topical nitrogen mustard monotherapy. Pediatric patients experienced no significant toxic effects with topical nitrogen mustard therapy.Topical nitrogen mustard remains an effective primary initial or salvage therapy in mycosis fungoides for patients with T1 and T2 disease. Long-term follow-up results confirm its safety.

    View details for Web of Science ID 000180971400006

    View details for PubMedID 12588222

  • Mycosis fungoides: radiation therapy. Dermatologic therapy Hoppe, R. T. 2003; 16 (4): 347-354

    Abstract

    Radiation therapy is the most effective single agent for the treatment of mycosis fungoides. There are well-defined dose-response relationships for achieving a complete response as well as the durability of this response. Techniques of electron beam therapy have been developed that permit treatment of the entire skin. Total-skin electron beam therapy is an important form of management, especially for patients who have thick generalized plaque or tumorous disease. Radiation therapy may also be used selectively for treatment of extracutaneous disease.

    View details for PubMedID 14686978

  • Hodgkin's disease: A model for interdisciplinary cancer management: 2002 Janeway Lecture CANCER JOURNAL Hoppe, R. T. 2002; 8 (6): 425-431

    View details for Web of Science ID 000180031900002

    View details for PubMedID 12500848

  • Management with topical nitrogen mustard in mycosis fungoides: Update of the Stanford experience Kim, Y. H., Hoppe, R. T. NATURE PUBLISHING GROUP. 2002: 234–34
  • Long-term follow-up after total lymphoid irradiation in pediatric heart transplant recipients JOURNAL OF HEART AND LUNG TRANSPLANTATION Chin, C., Hunt, S., Robbins, R., Hoppe, R., Reitz, B., Bernstein, D. 2002; 21 (6): 667-673

    Abstract

    Total lymphoid irradiation (TLI) is used to treat recurrent allograft rejection. Short-term success and complication rates have been reported in pediatric and adult cardiac transplant populations. We report the long-term efficacy and safety of TLI in treating intractable rejection in pediatric patients.Eight pediatric patients were treated with TLI (7 for recurrent rejection, 1 for risk of medication non-compliance). Therapy consisted of a mid-plane dose of 8 Gy administered with a 6-MeV linear accelerator using an anterior-posterior opposed technique. We reviewed outcomes for a total of 40 patient-years of follow-up.We encountered rejection (>Grade 2 by International Society for Heart and Lung Transplantation criteria) in 56.7% +/- 34.7% of biopsies performed within 90 days before TLI. Rejection rates dropped to 3.1% +/- 8.8% within the first 90 days (p < 0.005) after therapy and remained low at 5.6% +/- 1.3% (p < 0.05) during the first year after completion of TLI. Median time from TLI to the first subsequent rejection episode was 305 days (range, 77-1,920 days). Long-term follow-up (>3 years) of 5 patients demonstrated a continuing low incidence of rejection. Non-Hodgkin's lymphoma was diagnosed in 1 of 8 patients, graft coronary artery disease in 4 of 8 patients, and restrictive cardiomyopathy in 1 of 8 patients after TLI.Total lymphoid irradiation is an effective treatment for recurrent rejection and has short- and long-term efficacy. Morbid events may include cancer, graft coronary artery disease, and restrictive cardiomyopathy.

    View details for Web of Science ID 000176074500008

    View details for PubMedID 12057700

  • Mixed chimerism and immunosuppressive drug withdrawal after HLA-mismatched kidney and hematopoietic progenitor transplantation TRANSPLANTATION Millan, T. L., Shizuru, J. A., Hoffmann, P., Dejbakhsh-Jones, S., Scandling, J. D., GRUMET, F. C., Tan, J. C., Salvatierra, O., Hoppe, R. T., Strober, S. 2002; 73 (9): 1386-1391

    Abstract

    Rodents and dogs conditioned with total-lymphoid irradiation (TLI), with or without antithymocyte globulin (ATG), have been shown to develop mixed chimerism and immune tolerance without graft-versus-host disease (GVHD) after the infusion of major histocompatability complex (MHC)-mismatched donor bone marrow cells given alone or in combination with an organ allograft.Four human leukocyte antigen (HLA)-mismatched recipients of living donor kidney transplants were conditioned with TLI and ATG posttransplantation and infused with cyropreserved donor granulocyte colony-stimulating factor (G-CSF) "mobilized" hematopoietic progenitor (CD34+) cells (3-5x10(6) cells/kg) thereafter. Maintenance prednisone and cyclosporine dosages were tapered, and recipients were monitored for chimerism, GVHD, graft function, T-cell subsets in the blood, and antidonor reactivity in the mixed leukocyte reaction (MLR).Three of the four patients achieved multilineage macrochimerism, with up to 16% of donor-type cells among blood mononuclear cells without evidence of GVHD. Prolonged depletion of CD4+ T cells was observed in all four patients. Rejection episodes were not observed in the three macrochimeric recipients, and immunosuppressive drugs were withdrawn in the first patient by 12 months. Prednisone was withdrawn from a second patient at 9 months, and cyclosporine was tapered thereafter.Multilineage macrochimerism can be achieved without GVHD in HLA-mismatched recipients of combined kidney and hematopoietic progenitor transplants. Conditioning of the host with posttransplant TLI and ATG was nonmyeloablative and was not associated with severe infections. Recipients continue to be studied for the development of immune tolerance.

    View details for Web of Science ID 000175933100002

    View details for PubMedID 12023614

  • Primary radiotherapy for localized orbital malt lymphoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Le, Q. T., Eulau, S. M., George, T. I., Hildebrand, R., Warnke, R. A., Donaldson, S. S., Hoppe, R. T. 2002; 52 (3): 657-663

    Abstract

    To define the natural history, prognosis, and radiocurability of localized orbital extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT).Clinical records and pathologic material of 40 patients treated with local radiotherapy for localized orbital lymphoma were reviewed. Treatment consisted of 30-40 Gy in 1.8-2-Gy fractions (mean 34 Gy) of irradiation using 9-20-MeV electrons for conjunctival lesions, or 6-MV photons with complex treatment planning for retrobulbar lesions. The lens was routinely shielded with the use of a suspended eye bar.Upon pathologic review, 31 cases of orbital MALT lymphoma were identified. With the median follow-up of 5.9 years (range 9 months-0.3 years), the actuarial 10-year overall survival was 73%. Local control was 100%. Five distant failures resulted in a projected 10-year freedom from relapse of 71%. Most of the failures were extranodal in sites where MALT lymphoma has previously been shown to arise. No difference in outcome was observed among patients treated to less than or equal to 34 Gy vs. those treated to higher radiation doses. Two patients experienced clinically significant retinal damage after doses > or = Gy.In this study, localized orbital MALT lymphoma was well controlled with radiotherapy. Even following relapse, patients with orbital MALT lymphoma exhibited an indolent course. Relapse occurred predominantly in extranodal mucosal sites, implying a possible homing mechanism for MALT lymphoma cells. Given the excellent local control rates, our current treatment recommendation is to use a radiation dose of 30-30.6 Gy in 1.5-.8-Gy fractions to minimize risk of late toxicity.

    View details for PubMedID 11849787

  • Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: Mature results of a prospective clinical trial JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Hoppe, R. T., Breslin, S., Bartlett, N. L., Brown, B. W., Rosenberg, S. A. 2002; 20 (3): 630-637

    Abstract

    To provide more mature data on the efficacy and complications of a brief, dose-intense chemotherapy regimen plus radiation therapy (RT) to bulky disease sites for locally extensive and advanced-stage Hodgkin's disease.One hundred forty-two patients with stage III or IV or locally extensive mediastinal stage I or II Hodgkin's disease received Stanford V chemotherapy for 12 weeks followed by 36-Gy RT to initial sites of bulky (> or =5 cm) or macroscopic splenic disease. Freedom from progression (FFP), overall survival (OS), and freedom from second relapse (FF2R) were determined using life-table estimates. Outcomes were analyzed according to the international prognostic score. Late effects of treatment were recorded in follow-up.With a median follow-up of 5.4 years, the 5-year FFP was 89% and the OS was 96%. No patient progressed during treatment, and there were no treatment-related deaths. FFP was significantly superior among patients with a prognostic score of 0 to 2 compared with those with a score of 3 and higher (94% v 75%, P <.0001). No secondary leukemia was observed. To date, there have been 42 pregnancies after treatment. Among 16 patients who relapsed, the FF2R was 69% at 5 years.These data confirm our preliminary report that Stanford V chemotherapy with RT to bulky disease sites is highly effective in locally extensive and advanced Hodgkin's disease. It is most important to compare this approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the ongoing intergroup trial (E2496) to determine whether Stanford V with or without RT represents a therapeutic advance.

    View details for Web of Science ID 000173669400007

    View details for PubMedID 11821442

  • NCCN: Non-Hodgkin's lymphoma. Cancer control Zelenetz, A. D., Hoppe, R. T. 2001; 8 (6): 102-113

    View details for PubMedID 11760551

  • Natural killer/natural killer-like T-Cell lymphoma, CD56+, presenting in the skin: An increasingly recognized entity with an aggressive course JOURNAL OF CLINICAL ONCOLOGY Mraz-Gernhard, S., Natkunam, Y., Hoppe, R. T., Leboit, P., Kohler, S., Kim, Y. H. 2001; 19 (8): 2179-2188

    Abstract

    To describe and identify the clinical and pathologic features of prognostic significance for natural killer (NK) and NK-like T-cell (NK/T-cell) lymphoma presenting in the skin.This study was a retrospective review of 30 patients with CD56+ lymphomas initially presenting with cutaneous lesions, with analysis of clinical and histopathologic parameters.The median survival for all patients was 15 months. Those with extracutaneous manifestations at presentation (11 patients) had a shorter median survival of 7.6 months as compared with those without extracutaneous involvement (17 patients), who had a more favorable median survival of 44.9 months (P =.0001). Age, gender, extent of cutaneous involvement, and initial response to therapy had no statistically significant effect on survival. Seven patients (24%) had detectable Epstein-Barr virus (EBV) within neoplastic cells. The patients with tumor cells that coexpress CD30 (seven patients) have not yet reached a median survival after 35 months of follow-up as compared with those with CD30- tumor cells (20 patients), who had a median survival of 9.6 months (P <.02). Routine histopathologic characteristics had no prognostic significance nor did the presence of CD3epsilon, EBV, or multidrug resistance.NK/T-cell lymphoma is an aggressive neoplasm; however, a subset with a more favorable outcome is identified in this study. The presence of extracutaneous disease at presentation is the most important clinical variable and portends a poor prognosis. The extent of initial skin involvement does not reliably predict outcome. Patients from the United States with NK/T-cell lymphoma presenting in the skin have a low incidence of demonstrable EBV in their tumor cells. Patients with coexpression of CD30 in CD56 lymphomas tend to have a more favorable outcome.

    View details for Web of Science ID 000168178300009

    View details for PubMedID 11304770

  • Clinical characteristics and outcome of patients with extracutaneous mycosis fungoides JOURNAL OF CLINICAL ONCOLOGY de Coninck, E. C., Kim, Y. H., Varghese, A., Hoppe, R. T. 2001; 19 (3): 779-784

    Abstract

    To identify prognostic factors predictive of outcome in patients with extracutaneous (stage IV) mycosis fungoides (MF) and to evaluate the risk of progression to extracutaneous disease by initial extent of skin involvement.One hundred twelve patients with extracutaneous disease at presentation or with progression and 434 patients with initial cutaneous-only disease were identified. Actuarial survival curves were plotted according to the Kaplan-Meier technique.The median survival of all stage IV patients was 13 months from the date of first treatment for stage IV disease. Sex, race, age, extent of skin involvement, and peripheral blood Sezary cell involvement were not significant to survival outcome. Eleven patients (10%) had a complete response to therapy resulting in a significantly improved median survival compared with patients with a partial or no response (1.70 v 0.91 years, P =.047 and 1.70 v 0.57 years, P =.011, respectively). At 20 years from diagnosis, the risk for progression to extracutaneous disease by initial extent of skin involvement was 0% for limited patch/plaque, 10% for generalized patch/plaque, 35.5% for tumorous disease, and 41% for erythrodermic involvement.This was a larger scale study over a longer time period than had been completed previously on extracutaneous MF. Prognostic factors important in the cutaneous stages of disease are no longer significant once extracutaneous disease develops. Patients who had a more favorable response to therapy may have had a biologically less aggressive disease than their less fortunate counterparts. The risk of developing stage IV MF is highest in patients presenting with tumorous or erythrodermic skin disease and is lowest in patients with limited skin involvement.

    View details for Web of Science ID 000166803100024

    View details for PubMedID 11157031

  • High-dose therapy and autologous bone marrow transplantation for follicular lymphoma in first complete or partial remission: results of a phase II clinical trial BLOOD Horning, S. J., Negrin, R. S., Hoppe, R. T., Rosenberg, S. A., Chao, N. J., Long, G. D., Brown, B. W., Blume, K. G. 2001; 97 (2): 404-409

    Abstract

    Advanced stage follicular small cleaved and mixed cell lymphoma is characterized by relapse from remission and survival ranging from 6 to 12 years. Because young patients have the greatest compromise in longevity, the efficacy and toxicity of high-dose radiochemotherapy and bone marrow transplantation after conventional chemotherapy was evaluated in a prospective phase II clinical trial. Thirty-seven patients in a minimal disease state after conventional chemotherapy received fractionated total body irradiation and high-dose etoposide and cyclophosphamide, followed by purged autologous bone marrow. A reference sample of 188 patients of similar age, stage, and histology managed at this institution before 1988 was identified for comparison of patient characteristics and outcomes. Compared with reference patients, transplant recipients had a higher tumor burden at diagnosis. With a median follow-up of 6.5 years, the estimated 10-year survival after transplantation was 86%. There was a single lymphoma death yielding a 10-year disease-specific survival of 97%. There were 2 early transplant-related deaths and 2 late acute leukemia deaths. Ten patients relapsed, one with microscopic disease only. High tumor burden at diagnosis and incomplete response to chemotherapy adversely influenced survival in the reference but not in the transplanted patients. The estimated risk of death of 14% and relapse of 30% at 10 years in our transplanted follicular lymphoma patients, the majority of whom had high tumor burdens, compares favorably with our observations in appropriately matched reference patients.

    View details for Web of Science ID 000166388000011

    View details for PubMedID 11154216

  • High-dose therapy and autologous hematopoietic-cell transplantation for follicular lymphoma beyond first remission: The Stanford University experience BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Cao, T. M., Horning, S. F., Negrin, R. S., Hu, W. W., Johnston, L. F., Taylor, T. L., Shizuru, J. A., Hoppe, R. T., Brown, B. W., Blume, K. G., Stockerl-Goldstein, K. 2001; 7 (5): 294-301

    Abstract

    A retrospective analysis was performed to investigate the outcome of high-dose therapy (HDT) and autologous hematopoietic cell transplantation in patients with follicular lymphomas beyond first remission. Ninety-two patients with primary induction failure or relapsed follicular low-grade lymphoma (FLGL), follicular large cell lymphoma (FLCL), and transformed follicular lymphoma (TFL) were treated with myeloablative therapy consisting of etoposide (60 mg/kg), cyclophosphamide (100 mg/kg), and either carmustine (BCNU;15 mg/kg) or fractionated total body irradiation (FTBI; 1200 cGy) followed by transplantation of purged autologous bone marrow or peripheral blood hematopoietic cells. For the 49 patients with relapsed FLGL, the median age was 49 years and the median interval from diagnosis to HDT was 30 months. The 4-year estimate of overall survival (OS) was 60% (95% confidence interval [CI], 45%-75%) and of disease-free survival (DFS) was 44% (95% CI, 29%-59%). Treatment with the FTBI-containing HDT regimen was associated with significantly longer DFS (P = .04) and OS (P = .04) in our multivariate analysis. OS was also significantly longer among those treated with 3 or fewer chemotherapy regimens. For the 26 FLCL patients, the median age was 51 years and in 31% the indication for HDT was primary induction failure. For FLCL patients, the 4-year estimate of OS was 58% (95% CI, 37%-79%) and of DFS was 51% (95% CI, 30%-72%). Among the 17 patients with TFL, 13 (76%) transformed at first relapse, and only 6 patients (35%) achieved complete remission with salvage therapy prior to HDT. For TFL patients, the 4-year estimate of OS was 50% (95% CI, 24%-76%) and of DFS 49% (95% CI, 20%-78%). There were 3 occurrences of myelodysplasia (1 after treatment with TBI, 2 after BCNU treatment), yielding an estimated incidence of 7% (95% CI, 0%-16%) at 56 months. This analysis shows that relapsed FLGL patients treated with 3 or fewer different chemotherapy regimens show inferior survival. The HDT regimen containing FTBI appears to be superior to the BCNU-based regimen for relapsed FLGL, although longer follow-up is needed to evaluate late effects. Lastly, patients with TFL or induction failure and relapsed FLCL can achieve survival outcome comparable to those observed with the indolent follicular lymphomas.

    View details for Web of Science ID 000169118600007

    View details for PubMedID 11400952

  • Long-term follow-up of patients with Stage III follicular lymphoma treated with primary radiotherapy at Stanford University INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Murtha, A. D., Knox, S. J., Hoppe, R. T., Rupnow, B. A., Hanson, J. 2001; 49 (1): 3-15

    Abstract

    To report the long-term survival and late toxicity data of Stage III follicular lymphoma patients treated with primary radiotherapy.Sixty-six patients with Stage III follicular small cleaved (FSC) or follicular mixed (FM) non-Hodgkin's lymphoma were treated with total lymphoid irradiation (61 patients) or whole body irradiation (5 patients) as their primary treatment modality from 1963 to 1982 at Stanford University. Adjuvant chemotherapy was given to 13 patients.Median follow-up was 9.5 years with a range of 0.5-24.3 years. Median overall survival, cause-specific survival, freedom from relapse, and event-free survival were 9.5, 18.9, 7.1, and 5.1 years, respectively. Few initial relapses or lymphoma-related deaths were seen beyond the first decade of follow-up. Patient age and number of disease sites were the two strongest predictors of overall survival. The cohort of patients with limited Stage III disease demonstrated an 88% freedom from relapse and a 100% cause-specific survival with up to 23.5 years follow-up.The long-term survival data for Stage III FSC or FM non-Hodgkin's lymphoma treated with primary radiotherapy are at least comparable and possibly better than results achieved with other therapeutic approaches. Patients with limited Stage III disease do particularly well. Whether these results are superior to an initial approach of deferred therapy until clinically indicated is currently unknown.

    View details for Web of Science ID 000166317300002

    View details for PubMedID 11163492

  • The clinical spectrum of cutaneous B-cell lymphomas (CBCL): Excellent prognosis for patients with disease limited to the skin. Mraz-Gernhard, S. M., Horwitz, S., Kim, Y. H., Kohler, S., Hoppe, R. AMER SOC HEMATOLOGY. 2000: 329A
  • Rituximab is active in lymphocyte predominance Hodgkin's disease. Lucas, J. B., Hoppe, R. T., Horwitz, S. M., Breslin, S., Horning, S. J. AMER SOC HEMATOLOGY. 2000: 831A
  • Natural killer/natural killer-like T-cell lymphoma (CD56+) presenting in the skin: A study of clinical and pathologic characteristics affecting survival. Mraz-Gernhard, S. M., Hoppe, R. T., Natkunam, Y., Leboit, P., Kohler, S., Kim, Y. H. AMER SOC HEMATOLOGY. 2000: 124A–125A
  • Assessment of the Stanford V regimen and consolidative radiotherapy for bulky and advanced Hodgkin's disease: Eastern Cooperative Oncology Group Pilot Study E1492 JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Wiliams, J., Bartlett, N. L., Bennett, J. M., Hoppe, R. T., Neuberg, D., Cassileth, P. 2000; 18 (5): 972-980

    Abstract

    This study was performed, in a multi-institutional setting, to evaluate the efficacy and feasibility of the Stanford V chemotherapy regimen plus radiotherapy to bulky Hodgkin's disease sites.A two-stage design was implemented in a phase II study involving 47 patients with bulky mediastinal stage I/II or stage III/IV Hodgkin's disease. Twelve weeks of the Stanford V chemotherapy regimen were given with consolidative radiotherapy (36 Gy) to lymph nodes >/= 5 cm and/or macroscopic splenic disease. Treatment was administered in one of five institutions participating in the Eastern Cooperative Oncology Group.With a median follow-up of 4.8 years, 45 patients are alive and 40 have been continuously disease-free. The estimated freedom from progression was 87% at 2 years and 85% at 5 years. Overall survival was 96% at 2 and 5 years. There was one death from Hodgkin's disease and one death from an M5 acute leukemia. Six of seven relapsed patients received high-dose therapy and autologous stem-cell transplantation. The freedom from second progression for the seven relapsed patients was estimated at 98% at 3 years.Stanford V chemotherapy and consolidative radiotherapy to bulky disease is effective in bulky and advanced Hodgkin's disease in a multi-institutional setting. On this basis, an Intergroup study comparing doxorubicin, bleomycin, vinblastine, and dacarbazine with the Stanford V regimen has been initiated.

    View details for Web of Science ID 000085586000005

    View details for PubMedID 10694546

  • Management of breast cancer after Hodgkin's disease 39th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Wolden, S. L., Hancock, S. L., Carlson, R. W., Goffinet, D. R., Jeffrey, S. S., Hoppe, R. T. AMER SOC CLINICAL ONCOLOGY. 2000: 765–72

    Abstract

    To evaluate the incidence, detection, pathology, management, and prognosis of breast cancer occurring after Hodgkin's disease.Seventy-one cases of breast cancer in 65 survivors of Hodgkin's disease were analyzed.The median age at diagnosis was 24.6 years for Hodgkin's disease and 42.6 years for breast cancer. The relative risk for invasive breast cancer after Hodgkin's disease was 4.7 (95% confidence interval, 3.4 to 6. 0) compared with an age-matched cohort. Cancers were detected by self-examination (63%), mammography (30%), and physician exam (7%). The histologic distribution paralleled that reported in the general population (85% ductal histology) as did other features (27% positive axillary lymph nodes, 63% positive estrogen receptors, and 25% family history). Although 87% of tumors were less than 4 cm, 95% were managed with mastectomy because of prior radiation. Two women underwent lumpectomy with breast irradiation. One of these patients developed tissue necrosis in the region of overlap with the prior mantle field. The incidence of bilateral breast cancer was 10%. Adjuvant systemic therapy was well tolerated; doxorubicin was used infrequently. Ten-year disease-specific survival was as follows: in-situ disease, 100%; stage I, 88%; stage II, 55%; stage III, 60%; and stage IV, zero.The risk of breast cancer is increased after Hodgkin's disease. Screening has been successful in detecting early-stage cancers. Pathologic features and prognosis are similar to that reported in the general population. Repeat irradiation of the breast can lead to tissue necrosis, and thus, mastectomy remains the standard of care in most cases.

    View details for Web of Science ID 000085401800008

    View details for PubMedID 10673517

  • Toxicity of high-dose sequential chemotherapy and purged autologous hematopoietic tell transplantation precludes its use in refractory/recurrent non-Hodgkin's lymphoma BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Johnston, L. J., Stockerl-Goldstein, K. E., Hu, W. W., Negrin, R. S., Hoppe, R. T., Blume, K. G., Horning, S. J. 2000; 6 (5A): 555-562

    Abstract

    We conducted a pilot study in 20 patients with high-risk or recurrent/refractory non-Hodgkin's lymphoma (NHL) using high-dose sequential chemotherapy (HDSC) and autologous hematopoietic cell transplantation (AHCT). After cytoreduction with standard salvage therapy, HDSC/AHCT was administered in 4 phases at 2- to 4-week intervals. Phase 1 consisted of cyclophosphamide 7 g/m2 followed by granulocyte colony-stimulating factor (G-CSF) at 10 microg/kg per day and leukapheresis upon recovery from white blood cell nadir. The hematopoietic cell product was enriched by Percoll gradient separation and purged with a B-cell or T-cell monoclonal antibody panel and complement. Phase 2 consisted of methotrexate 8 g/m2 with leucovorin rescue and vincristine 1.4 mg/m2. Phase 3 was etoposide 2 g/m2 with G-CSF 5 microg/kg per day. In phase 4, the preparative regimen of mitoxantrone 60 mg/m2 and melphalan 180 mg/m2 was administered followed by AHCT. The NHL histologies were diffuse large cell, follicular/diffuse mixed, small noncleaved cell, T-cell-rich B-cell, lymphoblastic, and peripheral T cell. The remission status was first partial remission (PR1; n = 1) or beyond first complete remission (post-CR1; n = 19). Of the 20 patients enrolled, 11 proceeded through all 4 phases. Nine were removed from the study after the first or second phase because of progressive disease (n = 5), poor hematopoietic cell mobilization (n = 1), excessive toxicity (n = 2), and chronic active hepatitis C (n = 1). Treatment-related toxicities in the remaining 11 transplant recipients were cardiomyopathy, hemorrhagic cystitis, persistent cytopenias, acute renal failure, abnormal liver function test results, and infectious complications. There were no treatment-related deaths. Eight of the 11 transplant recipients were alive, 6 without disease, at a median follow-up of 2.7 years. The estimated median 2-year event-free survival was 55%, and overall survival was 70%. We conclude that HDSC/AHCT in refractory/recurrent NHL is associated with considerable acute and chronic toxicities. Given the toxicity profile, efficacy data were not sufficiently promising to warrant further study.

    View details for Web of Science ID 000090107100004

    View details for PubMedID 11071261

  • The Janeway lecture. Hodgkin's disease--finding the balance between cure and late effects. cancer journal from Scientific American Donaldson, S. S., Hancock, S. L., Hoppe, R. T. 1999; 5 (6): 325-333

    Abstract

    The purpose of this review is to summarize the Stanford experience in Hodgkin's disease, the late effects of treatment, and strategies to improve management to maximize cure and decrease late effects in these patients.Between 1960 and 1999, 2617 consecutive patients with Hodgkin's disease have been seen, treated, and rigorously followed at Stanford. This population includes patients of all ages and stages of disease. The database summarizing this experience serves as the source of survival and mortality data over 4 decades. Two thousand two hundred thirty-two of the population comprise the group evaluated for secondary cardiac disease. Two thousand one hundred sixty-two patients have been evaluated for risk of secondary leukemia, non-Hodgkin's lymphoma, and solid tumors. Eight hundred eighty-five women were evaluated for secondary breast cancer, prompting a subsequent analysis of risk of secondary cancer among 694 pediatric patients.The probability of cure of Hodgkin's disease has dramatically improved over the past 40 years. Today, 94% of patients are expected to survive. Among those who do not survive, approximately half die of Hodgkin's disease, 20% of new cancers, and 14% of cardiovascular complications. Modifications in patient management and treatment have greatly reduced the serious late effects observed from prior therapy. With current combined-modality therapy using moderate doses of involved field of radiation and limited cycles of multiagent, risk adapted chemotherapy, serious cardiac complications and development of secondary cancers are expected to be greatly reduced. The Stanford 25-year pediatric Hodgkin's disease experience reveals that survival in favorable early-stage disease exceeds 95%. Newer protocols for children with advanced-stage disease continue to show these excellent survival rates and promise less late morbidity. Adult protocols using the risk-adapted Stanford V combined-modality program now parallel the pediatric experience, with greater than 90% survival in these patients.Thus today the likelihood of cure of Hodgkin's disease greatly exceeds the risk of late effects, a goal both Dr. Henry Janeway and Madame Marie Curie emphasized and taught from first-hand experience.

    View details for PubMedID 10606471

  • What is the significance of nasal involvement in nasopharyngeal carcinoma? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lin, Z. X., Li, D. R., Chen, Z. J., Zheng, M. Z., Shi, Y. Y., Lin, B. H., Kapp, D. S., Hoppe, R. T. 1999; 45 (4): 907-914

    Abstract

    The purpose of this study was to differentiate the patterns of nasal fossa involvement in nasopharyngeal carcinoma (NPC) and to clarify its prognostic influence on local control and survival after radiation therapy.Between November 1989 and July 1991, 218 patients with histologically proven local-regional NPC were treated with radiotherapy following the protocol at the Department of Radiation Oncology, Cancer Hospital, Shantou University School of Medicine. All patients had pretreatment CT scans. Fiberoptic endoscopic examination was performed every week during treatment and at the time of every follow-up visit to define the initial extent of disease and to evaluate treatment response. No chemotherapy or brachytherapy was given.Of the 218 patients, 87 had nasal involvement. Sixty of them had a pattern of mucosal infiltration (MI), another 27 had an exophytic protruding (EP) component. The likelihood of residual disease after irradiation, the local relapse rate, 5-year freedom from progression rate (FFP), and death rate associated with local relapse (DRALR) of MI and EP were 36.7% vs. 3.7%, 30.0% vs. 7.4%, 26.7% vs. 51.8%, and 25.0% vs. 3.7% with p<0.004, p<0.005, p<0.02, and p<0.03, respectively. Multivariate analysis in this selected group demonstrated that infiltration of nasal fossa mucosa was an independent prognostic factor on primary control and freedom from progression.Differentiation of nasal fossa involvement according to MI or EP is of value in predicting the outcome of treatment. We suggest that only the MI group should be considered as nasal involvement in the staging of NPC.

    View details for Web of Science ID 000083624000012

    View details for PubMedID 10571197

  • Epidermotropic cutaneous B-cell lymphoma mimicking mycosis fungoides JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Chui, C. T., Hoppe, R. T., Kohler, S., Kim, Y. H. 1999; 41 (2): 271-274

    Abstract

    Cutaneous involvement by B-cell lymphoma is often secondary to systemic disease. Primary cutaneous B-cell lymphomas are less common, and patients generally have an excellent prognosis. We present a patient with cutaneous B-cell lymphoma with clinical and histologic features mimicking mycosis fungoides. Although the patient was initially misdiagnosed as having a T-cell lymphoma, immunophenotypic studies demonstrated that this was a B-cell lymphoma.

    View details for Web of Science ID 000081921900023

    View details for PubMedID 10426903

  • Mycosis fungoides and the Sezary syndrome SEMINARS IN ONCOLOGY Kim, Y. H., Hoppe, R. T. 1999; 26 (3): 276-289

    Abstract

    Mycosis fungoides (MF) and the Sézary syndrome are a group of extranodal non-Hodgkin's lymphomas of T-cell origin with primary cutaneous involvement. The group distinguishes itself from other primary cutaneous T-cell lymphomas (CTCLs) by its unique clinical features and histopathology. In its early stages, it often resembles common benign dermatoses, and therefore, a definitive diagnosis can be delayed. The affected T cells are characterized by a predominant CD4+ phenotype with frequent loss of CD7 (pan-T-cell antigen) and often demonstrate T-cell receptor (TCR) rearrangement. The prognosis of patients with MF is highly dependent on the extent and type of skin involvement. The initial cutaneous presentation of MF can be patches, plaques, tumors, or erythroderma. Patients who present with limited patch/plaque disease have an outstanding prognosis with an overall long-term survival that is similar to the expected survival of a matched control population. It is exceedingly rare for patients who present with limited or generalized patch/plaque disease without peripheral lymphadenopathy to have extracutaneous involvement. Therefore, the staging evaluation differs for patients with MF versus patients with other non-Hodgkin's lymphomas and should be tailored to the clinical presentation. Patients who have tumorous or erythrodermic skin involvement have a less favorable prognosis, and patients who present with extracutaneous disease have a poor prognosis. There are multiple therapeutic options for patients with MF and the Sézary syndrome. Selection of a specific treatment plan is based primarily on the clinical stage of the disease. The primary therapy for patients with patch/plaque disease without extracutaneous involvement is a topical regimen, whereas chemotherapy or other aggressive systemic regimens are reserved for those with recalcitrant disease or extracutaneous involvement. There is no evidence that early aggressive systemic therapy is preferable to conservative therapy in the management of limited disease. There are newer combination topical and/or systemic regimens that result in an improved clinical response and possibly a prolonged response duration. For advanced disease, standard therapies are often palliative and successful clinical response is often very short-lived. Therefore, all patients with recalcitrant or extracutaneous disease should be considered for newer investigative therapies.

    View details for Web of Science ID 000080809400005

    View details for PubMedID 10375085

  • Total skin electron beam therapy with or without adjuvant topical nitrogen mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis fungoides 40th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Chinn, D. M., Chow, S., Kim, Y. H., Hoppe, R. T. ELSEVIER SCIENCE INC. 1999: 951–58

    Abstract

    To compare the efficacy of total skin electron beam therapy (TSEBT) with or without adjuvant topical nitrogen mustard (+/- HN2) with topical nitrogen mustard (HN2) alone as initial management of T2 and T3 mycosis fungoides (MF).A retrospective analysis of 148 patients presenting to Stanford from January, 1970 through January, 1995 within 4 months of pathologic diagnosis of MF. Fifty-five patients with T2 and 27 with T3 disease received TSEBT +/- HN2. Fifty-four patients with T2 and 12 with T3 disease received HN2 alone. Boosts with radiotherapy were usually administered to cutaneous tumors of patients with T3 disease.TSEBT +/- HN2 yielded significantly higher complete response (CR) rates than did HN2 alone in patients with T2 and T3 disease (76% vs 39%, p = 0.03 for T2, and 44% vs 8%, p < 0.05 for T3, respectively). In T2 disease, treatment with adjuvant HN2 was associated with a longer freedom from relapse following TSEBT when compared to observation following a CR to TSEBT (p = 0.068). However, no significant differences in survival were observed for different management programs for T2 or T3 disease. In T2 disease, both TSEBT and HN2 were as effective as salvage therapy as when utilized as initial therapy. However, salvage therapy in T3 disease was rarely effective. Limited tumor involvement in T3 disease did not correlate with improved survival compared to more generalized tumorous disease. MF contributed to 27% and 68% of deaths in patients with T2 and T3 disease, respectively.Because of high response rates, management of significantly symptomatic or extensive T2 MF should include TSEBT, and adjuvant HN2 should be administered after a CR to TSEBT. Patients with T2 disease who fail TSEBT or HN2 can be salvaged with the other modality. TSEBT is also an effective treatment for T3 disease. The small subset of patients with limited T3 disease may also be treated with HN2 and local radiotherapy to the tumors. Further investigations are necessary to improve the overall outcome for T3 mycosis fungoides.

    View details for Web of Science ID 000079279100002

    View details for PubMedID 10192339

  • Results of the 1988-1989 patterns of care study process survey for Hodgkin's disease INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Smitt, M. C., Stouffer, N., Owen, J. B., Hoppe, R. T., Hanks, G. E. 1999; 43 (2): 335-339

    Abstract

    To document national standards of care for patients receiving radiotherapy as part of curative treatment for Hodgkin's disease.A national survey was conducted of 61 institutions treating 275 patients with Stages I-III Hodgkin's disease and representing six facility type strata. Pretreatment evaluation, radiotherapy treatment parameters, and use of combined modality therapy were assessed.Ann Arbor stage for the 275 patients was as follows: IA, 69 (25%); IB, 7 (3%); IIA, 123 (45%); IIB, 36 (13%); IIIA 23 (8%), IIIB, 14 (5%); unknown, 3 (1%). Pretreatment evaluation included complete blood count for 93%, sedimentation rate in 29%, chest CT in 88%, abdominal CT scan in 87%, and bone marrow biopsy in 81%. Lymphangiograms were obtained in 50% of cases; laparotomy was performed in 46%. The yield of positive findings in the spleen at laparotomy was 6.5 % overall. Facility differences with respect to staging were seen only for the use of gallium scans, which were more commonly used in academic centers (44% vs. 15-23% elsewhere, p<0.001). Radiotherapy was delivered with a linear accelerator in 94% of cases. Treatment simulation was performed for 94% and individualized blocks constructed for 95% overall; however, freestanding facilities had a lower rate of performance of these procedures (78% vs. 98-99% for simulation and 88% vs. 96-99% for customized blocking, p<0.001). The mean supradiaphragmatic dose was 36.74 Gy and the mean subdiaphragmatic dose was 33.81 Gy. Planned combined modality therapy was given in 36% of patients. The use of combined modality therapy by stage was as follows: IA, 11%; IB, 43%; IIA, 30%; IIB, 68%; IIIA, 57%; IIIB, 100%. Chemotherapy was completed prior to radiation in 80% of cases and generally consisted of ABVD (32%), an alternating regimen (25%), or MOPP (22%). Among Stage I/II patients, use of chemotherapy was associated with reduced radiation doses (mean supradiaphragmatic dose 34.53 Gy vs. 38.43 Gy and mean subdiaphragmatic dose 31.27 Gy vs. 34.51 Gy), and reduced volumes of treatment (87% vs. 28% treated to one side of the diaphragm only). Laparotomy was not associated with decreased supra- or subdiaphragmatic radiation doses or decreased volumes of treatment.With the exception of gallium scans, pretreatment evaluation is relatively uniform across facility strata. Increased understanding of prognostic factors in Hodgkin's disease and greater use of planned combined modality therapy for higher risk patients appears to have contributed to a decreased use of and low yield of positive findings for laparotomy. Laparotomy was not associated with reduced radiation volumes or doses. Freestanding radiation facilities had a lower rate than other facility types for the performance of treatment simulation and customized patient blocking.

    View details for Web of Science ID 000078564800013

    View details for PubMedID 10030258

  • Clinical characteristics and long-term outcome of patients with generalized patch and/or plaque (T2) mycosis fungoides ARCHIVES OF DERMATOLOGY Kim, Y. H., Chow, S., Varghese, A., Hoppe, R. T. 1999; 135 (1): 26-32

    Abstract

    To study the long-term results of treatment of patients with generalized patch and/or plaque mycosis fungoides and to identify clinical characteristics predictive of survival and response to treatment.A single-center, 35.5-year retrospective cohort analysis.Private referral medical center.One hundred seventy-six patients with generalized patch and/or plaque (T2) mycosis fungoides.Long-term actuarial survival and freedom-from-relapse results as calculated by the Kaplan-Meier method.The long-term (35.5-year) survival of patients with T2 mycosis fungoides is worse than the expected survival of a race-, age-, and sex-matched control population (P<.001). The median survival of the T2 group is 11.7 years. Patients younger than 58 years (median age) at presentation have a more favorable overall and disease-specific survival than the patients who are 58 years or older (P<.001 vs P<.025). Patient sex or race had no significant effect on overall survival. Patients who presented with palpable clinically significant lymph nodes (stage IIA) had long-term survival results similar to those without lymphadenopathy (stage IB), despite improved freedom-from-relapse outcome for patients with stage IB. Twenty-four percent of patients who progressed to more advanced disease had a lower complete response rate to initial therapy than did other patients (21% vs 65%) (P<.001). Patients who received total skin electron beam therapy had a better complete response rate than patients treated with topical mechlorethamine hydrochloride alone; the relapse-free results were superior in patients with a total dose of 30 Gy or higher and in patients who received topical mechlorethamine as adjuvant therapy following total skin electron beam therapy. Despite differences in freedom-from-relapse results among different treatment groups, long-term overall or disease-specific survivals were not significantly different.A significant proportion (24%) of patients with generalized patch and/or plaque (T2) mycosis fungoides experience disease progression to a more advanced clinical stage, and nearly 20% eventually die of the disease. Younger patients have a more favorable disease-specific long-term outcome than patients who are older. Presence of lymphadenopathy (stage IIA) at diagnosis does not predict worse long-term survival outcome. Clinical features predictive of disease progression include initial lymphadenopathy (stage IIA) and lack of complete response to initial treatment. Despite superior complete response rate to a 30-Gy or higher dose of total skin electron beam therapy, topical mechlorethamine proves to be a cost-effective initial treatment for patients with T2 disease. The concept of an adjuvant therapy after irradiation is appealing, although it may not lead to improved long-term survival.

    View details for Web of Science ID 000078112200004

    View details for PubMedID 9923777

  • Role of histology in providing prognostic information in mycosis fungoides JOURNAL OF CUTANEOUS PATHOLOGY SMOLLER, B. R., Detwiler, S. P., Kohler, S., Hoppe, R. T., Kim, Y. H. 1998; 25 (6): 311-315

    Abstract

    Many patients who present with patch and early plaque stage mycosis fungoides follow an indolent course and survive for many years following diagnosis. A certain subset of patients, however, have rapidly progressive disease leading to accelerated demise. We examined 21 histologic sections from initial biopsies taken from patients with stable disease and 26 from patients with rapidly progressive disease in order to evaluate the role of histology in predicting the disease course. Two or three authors examined each case and scored each of 24 histologic parameters using a previously described four-point scale with no knowledge of the patients' clinical courses. Interobserver agreement was quite high. The only histologic parameter that demonstrated statistical differences between the two groups of patients was degree of acanthosis. The degree of spongiosis, number of eosinophils, amount of hyperconvolution of dermal lymphocytes and density of the dermal infiltrate approached statistical significance but did not attain this level. All of these differences were quite small. No differences were seen for the other 19 parameters. Patients with rapidly progressive disease tended to have more acanthosis, a few more hyperconvoluted dermal lymphocytes, a slightly greater number of eosinophils and perhaps a slightly more dense dermal infiltrate than patients who had stable disease. However, as all of these changes were very slight, it appears unlikely that evaluation of any single biopsy specimen for the histologic parameters we studied is helpful in predicting the prognosis for a specific patient.

    View details for Web of Science ID 000074683500005

    View details for PubMedID 9694620

  • Mycosis fungoides in young patients: Clinical characteristics and outcome JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Crowley, J. J., Nikko, A., Varghese, A., Hoppe, R. T., Kim, Y. H. 1998; 38 (5): 696-701

    Abstract

    Mycosis fungoides (MF) can begin as early as the first decade of life. Few studies have reviewed MF in younger patients and none has been large enough to assess prognosis and outcome.We reviewed the clinical characteristics, prognosis, factors related to disease progression, and therapy in patients with MF younger than 35 years of age.Fifty-eight patients were entered into this retrospective cohort analysis.Significantly fewer patients with MF who are younger than 35 years presented with erythroderma (T4) and more with limited patch/plaque (T1) disease than older patients. Duration of skin disease before diagnosis of MF did not vary between the two groups. The long-term survival of younger patients with MF is significantly decreased when compared with a race-, age-, and sex-matched control population (p < 0.001). Disease-specific survivals (DSS) of younger and older patients are similar, but young patients show a slight but significantly better overall DSS (p < 0.02). However, DSS comparison of generalized patch/plaque (T2) and tumor stage (T3) patients with MF showed no significant difference between young and old patients (p=0.47, p=0.59). Patient age was not a significant predictor of survival when controlled for T-stage. Sixteen of 58 young patients with MF have died, 13 because of MF (22%), compared with 138 of 500 older patients (28%) who died as a result of MF. All younger patients with MF who progressed had at least T2 disease at presentation. Fifty of 56 young patients with MF and T1-T3 disease were treated initially with total skin electron beam or topical nitrogen mustard. The response to therapy was similar in younger and older patients with MF.T1 disease is more common and T4 disease is unusual in young patients with MF compared with an older population of patients with MF. Young patients with T1 disease, all of whom were treated with either topical nitrogen mustard or total skin electron beam therapy, or both therapies, showed no disease progression. Overall, young patients with MF showed slightly better DSS, but this was because of differences in stage distribution.

    View details for Web of Science ID 000073485800006

    View details for PubMedID 9591813

  • Radiation therapy as a component of high-dose salvage strategies in Hodgkin's disease. Annals of oncology Hoppe, R. T. 1998; 9: S87-90

    Abstract

    The expected event-free survival for patients undergoing high-dose salvage therapy for Hodgkin's disease is 40%-60%. Three-quarters of these patients will relapse in prior sites of disease. Radiation therapy is a very effective local-regional modality in Hodgkin's disease. It is possible that the judicious use of radiation can improve the event-free survival of high-dose salvage programs. Retrospective analysis supports this concept, but the rationale should be incorporated and tested in prospective clinical trials.

    View details for PubMedID 9926244

  • Long-term results of total lymphoid irradiation in the treatment of cardiac allograft rejection 38th Annual Meeting of American-Society-for-Therapeutic-Radiology-and-Oncology Wolden, S. L., Tate, D. J., Hunt, S. A., Strober, S., Hoppe, R. T. ELSEVIER SCIENCE INC. 1997: 953–60

    Abstract

    To evaluate the short and long-term effects of total lymphoid irradiation (TLI) in the treatment of cardiac transplant rejection.Between 1986 and 1995, 48 courses of TLI were delivered to 47 cardiac transplant patients. In 37 patients, TLI was administered for intractable allograft rejection despite conventional therapy while 10 patients received TLI prophylactically. The prescribed radiation dose was 8 Gy in 0.8 Gy fractions twice weekly to mantle and inverted-Y plus spleen fields. Postirradiation follow-up ranged from 6 months to 9.1 years, with a mean of 3.1 years.The actual mean dose was 7.3 Gy delivered over a mean of 39 days. Fifty-six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, rejection rates dropped from 0.46 to 0.14 and to 0.06 episodes/patient/month before, during, and after TLI (p < 0.0001). Rejection rates continued to drop throughout follow-up. Prednisone requirements decreased from 0.41 mg/kg before treatment to 0.21 mg/kg afterward (p < 0.0001). The ratio of helper to cytotoxic-suppressor T-cells decreased during TLI from 1.33 to 0.89, and remained low at 0.44, 2-4 months after treatment. Infection rates were not increased and two patients developed malignancy. Rejection rates were high during prophylactic treatment and this protocol was abandoned. Three-year actuarial survival after irradiation was 60% for patients with intractable rejection and 70% for the prophylactic cohort.TLI is an effective treatment for control of intractable cardiac rejection. Episodes of rejection and steroid dosage requirements are decreased for up to 9.1 years. A possible mechanism of action is long term alteration in T-lymphocyte subsets. Patients experience transient bone marrow suppression but no increase in infection or bleeding. Long-term complications of TLI are not appreciably different than conventional immunosuppression.

    View details for Web of Science ID A1997YG83800002

    View details for PubMedID 9392531

  • Fractionated total-body irradiation, etoposide, and cyclophosphamide followed by allogeneic bone marrow transplantation for patients with high-risk or advanced-stage hematological malignancies. Biology of blood and marrow transplantation Long, G. D., Amylon, M. D., Stockerl-Goldstein, K. E., Negrin, R. S., Chao, N. J., Hu, W. W., Nademanee, A. P., Snyder, D. S., Hoppe, R. T., Vora, N., Wong, R., Niland, J., Reichardt, V. L., Forman, S. J., Blume, K. G. 1997; 3 (6): 324-330

    Abstract

    Myeloablative therapy followed by allogeneic bone marrow transplantation (BMT) has proven to be curative therapy in patients with hematologic malignancies. Relapse, however, remains a major cause of treatment failure for patients with advanced disease. During the past 15 years, we have gained considerable experience with the combination of fractionated total-body irradiation (FTBI) and etoposide followed by allogeneic BMT for hematologic malignancies. In an attempt to decrease post-transplant relapse rates, 67 patients under the age of 50 years with high-risk or advanced-stage hematological malignancies received an intensified regimen of FTBI and etoposide plus cyclophosphamide followed by BMT from a genotypically-matched related donor. The regimen consisted of 1320 cGy of FTBI in 11 fractions, 60 mg/kg of etoposide (VP-16), and 60 mg/kg of cyclophosphamide (CY). Fifty-three patients received cyclosporine and prednisone for graft-vs.-host disease (GVHD) prophylaxis and 14 patients received cyclosporine, methotrexate, and prednisone. Diagnosis at BMT included 45 patients with acute leukemia, 7 patients with chronic leukemia, and 15 patients with high-grade non-Hodgkin's lymphoma (NHL). Actuarial disease-free survival (DFS) at 3 years was 42% +/- 12% for the entire group with a median follow-up of 50 months (range 20-74) for 28 patients who remain alive in continued complete remission (CR). Actuarial 3-year-DFS was 38% +/- 14% in 52 patients with acute or chronic leukemia and 60% +/- 25% in 15 patients with NHL with relapse rates of 45% +/- 16% and 21% +/- 11%, respectively. DFS at 3 years was 40% +/- 18% in 32 patients with acute leukemia in 1st relapse or 2nd CR or chronic myelogenous leukemia in accelerated phase, and was 32% +/- 22% in 20 patients with more advanced disease. Regimen related mortality occurred in 9 patients (4, veno-occlusive disease of the liver; 2, multi-organ failure; 1, diffuse alveolar hemorrhage; 1, central nervous system (CNS) hemorrhage; 1, adult respiratory distress syndrome (ARDS). The combination of FTBI, etoposide, and cyclophosphamide followed by allogeneic BMT is an effective and relatively well-tolerated regimen for patients with advanced hematologic malignancies. The role for this regimen should be further defined by prospective clinical trials.

    View details for PubMedID 9502300

  • Long-term depletion of naive T cells in patients treated for Hodgkin's disease BLOOD Watanabe, N., DeRosa, S. C., Cmelak, A., Hoppe, R., Herzenberg, L. A., Herzenberg, L. A., Roederer, M. 1997; 90 (9): 3662-3672

    Abstract

    We investigated the representation of T cells in patients who had been treated for Hodgkin's disease (HD). We found a marked depletion in both CD4 and CD8 naive T-cell counts that persists up to 30 years after completion of treatment. In contrast, CD4 and CD8 memory T-cell subsets recovered to normal or above normal levels by 5 years posttreatment. Thus, the previously-reported long-term deficit in total CD4 T-cell counts after treatment for HD is due to specific depletion of naive T cells. Similarly, total CD8 T-cell counts return to normal by 5 years only because CD8 memory T cells expand to higher than normal levels. These findings suggest that the treatment (mediastinal irradiation) results in a longterm dysregulation of T-cell subset homeostasis. The profound depletion of naive T cells may explain the altered T-cell function in treated patients, including the poor response to immunization after treatment for HD. Further, in some individuals, we identified expansions of unusual subsets expressing low levels of CD8. Eight-color fluorescence-activated cell sorting analyses showed that these cells largely express CD8alphaalpha homodimers and CD57, consistent with the phenotype of potentially extrathymically derived T cells. In addition, these cells, both CD4+ and CD4-, are probably cytotoxic lymphocytes, as they express high levels of intracellular perforin. In adults treated for HD, an increased activity of extrathymic T-cell differentiation may partially compensate for the loss of thymic-derived T cells.

    View details for Web of Science ID A1997YD10800043

    View details for PubMedID 9345051

  • Non-Hodgkin's lymphoma of the paranasal sinuses: Clinical and pathological features, and response to combined-modality therapy CANCER JOURNAL Hausdorff, J., Davis, E., Long, G., Hoppe, R., VANDERPAS, M., Lassman, C., Kamel, O., Jacobs, C. 1997; 3 (5): 303-311

    Abstract

    Lymphomas of the paranasal sinuses may have poorer prognoses compared with other extranodal lymphomas of the head and neck, and are not well defined as a particular clinicopathologic entity. The outcome of combined-modality therapy and central nervous system (CNS) prophylaxis has not been fully determined.We retrospectively reviewed our experience with 16 consecutive, carefully defined patients, all treated with both chemotherapy and radiotherapy.There were 11 men and five women, mean age 52. All presented with local symptoms; 13 had stage I or II disease. Thirteen had diffuse large cell lymphoma, two diffuse mixed, and one small noncleaved. Phenotyping revealed 10 B-cell, four T-cell, and two T or natural killer (NK). Most received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy; the order of chemotherapy and radiotherapy varied. Twelve received CNS prophylaxis. Of 12 complete responses, six relapsed, all at distant sites, and two died during initial therapy. Five-year survival was 29%, and median survival 18 months. Four of 10 B-lineage patients were relapse-free at 4 years; all six T- or T/NK-lineage patients relapsed or were dead within 6 months. Tumors of T or NK lineage often expressed CD56 and showed evidence of Epstein-Barr viral infection; otherwise, pathological features were not predictive of lineage or outcome. Neither age nor lactate dehydrogenase predicted prognosis. No complete responder recurred in the CNS as site of first relapse.Despite localized stage at presentation, sinus lymphoma is an aggressive disease, characterized by distant relapse and early mortality. Combined-modality therapy with CNS prophylaxis improves outcome compared with radiotherapy alone; however, prognosis remains poor. Patients with T-lineage disease appear to have a particularly bad outcome. Autologous bone marrow transplantation should be evaluated as first-line therapy for those at high risk of relapse.

    View details for Web of Science ID A1997XX75500011

    View details for PubMedID 9327155

  • Stanford-Kaiser permanente G1 study for clinical stage I to IIA Hodgkin's disease: Subtotal lymphoid irradiation versus vinblastine, methotrexate, and bleomycin chemotherapy and regional irradiation JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Hoppe, R. T., Mason, J., Brown, B. W., Hancock, S. L., Baer, D., Rosenberg, S. A. 1997; 15 (5): 1736-1744

    Abstract

    We have demonstrated that a relatively mild chemotherapy regimen, vinblastine, methotrexate, and bleomycin (VBM), and involved-field radiotherapy (IFRT) could substitute for extended-field radiotherapy in patients with favorable Hodgkin's disease (HD) who have been laparotomy-staged. The purpose of this study is to determine if VBM and regional radiotherapy can substitute for extended-field radiotherapy in favorable clinical stage (CS) I and II HD.Seventy-eight patients with favorable CS I to II HD were randomly assigned to subtotal lymphoid irradiation (STLI) or VBM chemotherapy and regional radiotherapy. Randomization was stratified on the basis of age, sex, number of Ann Arbor sites, histology, and institution. Patients were evaluated for freedom from progressive HD, survival, and toxicity. Results were compared with the predecessor trial in pathologically staged patients.With a median follow-up period of 4 years, the rate of freedom from progressive HD was 92% (95% confidence interval [CI], 88% to 96%) for patients treated with STLI and 87% (95% CI, 81% to 93%) for patients treated with VBM and regional radiotherapy. Six of seven patients who relapsed are alive and in remission following successful second-line therapy.Given the caveat of a small number of patients, the results of extended-field radiotherapy and VBM and regional radiotherapy are comparable with a median follow-up period of 4 years. VBM serves as a paradigm to reduce late effects in favorable early-stage HD. We do not advocate its routine use in clinical practice, but instead encourage participation in clinical trials with the objective of maintaining efficacy while reducing toxicity in CS I and II HD.

    View details for Web of Science ID A1997WZ56400006

    View details for PubMedID 9164180

  • Detection of relapse in early-stage Hodgkin's disease: Role of routine follow-up studies 37th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology TORREY, M. J., Poen, J. C., Hoppe, R. T. AMER SOC CLINICAL ONCOLOGY. 1997: 1123–30

    Abstract

    To examine the costs and benefits of routine follow-up evaluation in patients treated with radiation therapy for early-stage Hodgkin's disease.We retrospectively examined patterns of follow-up evaluation and methods of relapse detection among 709 patients with stage I and II Hodgkin's disease treated with primary radiotherapy between 1969 and 1994. We determined the probability of relapse detection for seven routine follow-up procedures, compared their relative costs, and determined the impact of each procedure on the likelihood of survival following salvage therapy.Relapse has occurred in 157 patients (22%) at a median 1.9 years (range, 0 to 13 years) posttreatment. Relapse was suspected primarily by history (Hx) in 55% of patients, physical examination (PE) in 14%, chest x-ray (CXR) in 23%, and abdominal x-ray (KUB) in 7%. Only one relapse (1%) was identified by a routine laboratory study. The rate of relapse detection was highest for a combination of Hx and PE (78 of 10,000 examinations) followed by CXR (26 of 10,000 examinations). The projected charges (1995 dollars) per relapse detected by routine follow-up Hx and PE were $11,000 compared with $68,000 for CXR and $142,000 for KUB. The 10-year actuarial survival rate following salvage therapy was 65% overall, 65% for patients in whom relapse was detected by Hx or PE, and 69% for patients in whom relapse was detected by radiographs (P = not significant).The majority of relapses occurred within 5 years of treatment and were identified by Hx and PE. CXR was useful during the first 3 years of follow-up evaluation. KUB, CBC, and laboratory studies accounted for nearly half of all follow-up charges and rarely led to the detection of relapse. Their routine use as a method of relapse detection is questionable. In general, the method of relapse detection did not have a significant impact on the likelihood of successful salvage therapy.

    View details for Web of Science ID A1997WN19000034

    View details for PubMedID 9060554

  • Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin's disease BLOOD Yuen, A. R., Rosenberg, S. A., Hoppe, R. T., HALPERN, J. D., Horning, S. J. 1997; 89 (3): 814-822

    Abstract

    Sixty patients with Hodgkin's disease, refractory to or at first recurrence after chemotherapy, received cytoreductive therapy followed by high-dose etoposide, cyclophosphamide and either total body irradiation or carmustine and autografting (median follow-up, 3.6 years; range, 1.1 to 7.5 years). A matched conventional salvage group of 103 patients was selected from patients treated at Stanford University Medical Center between January 1976 and January 1989 (median follow-up, 10.3 years; range, 3.0 to 15.7 years). Overall survival (OS), event-free survival (EFS), and freedom from progression (FFP) at 4 years follow-up favored patients who received high-dose therapy compared with conventional salvage treatment (OS: 54% v 47%, P = .25; EFS: 53% v 27%, P < .01; FFP: 62% v 32%, P < .01). In Cox regression analysis, response to cytoreductive or salvage therapy and B symptoms at relapse were the most important predictors of OS. The use of high-dose therapy at relapse, a longer duration of remission, and favorable response to cytoreductive or salvage therapy were most predictive of superior FFP and EFS. These data from a single institution comparing conventional and high-dose therapy in matched patients demonstrate an advantage for high-dose therapy and autografting in the sustained control of Hodgkin's disease. As with primary therapy, it is difficult to demonstrate a statistically significant survival advantage, despite an apparently superior cure rate. However, patients failing induction therapy or relapsing within 1 year benefited significantly from high-dose therapy by all outcome measures (OS, EFS, FFP). As the transplant-related mortality rates decline in Hodgkin's disease, it is predicted that cure rates and late effects will become ultimate determinants of the success of high-dose therapy and autografting.

    View details for Web of Science ID A1997WG07300009

    View details for PubMedID 9028312

  • High-dose therapy and autologous hematopoietic progenitor cell transplantation for recurrent or refractory Hodgkin's disease: Analysis of the Stanford University results and prognostic indices BLOOD Horning, S. J., Chao, N. J., Negrin, R. S., Hoppe, R. T., Long, G. D., Hu, W. W., Wong, R. M., Brown, B. W., Blume, K. G. 1997; 89 (3): 801-813

    Abstract

    One hundred nineteen patients with relapsed or refractory Hodgkin's disease (HD) received high-dose therapy followed by autologous hematopoietic progenitor cell transplantation. Three preparatory regimens, selected on the basis of prior therapy and pulmonary status, were employed. Twenty-six patients without a history of prior chest or pelvic irradiation were treated with fractionated total body irradiation, etoposide (VP) 60 mg/kg and cyclophosphamide (Cy) 100 mg/kg. Seventy-four patients received BCNU 15 mg/kg with identical doses of VP and Cy. A group of 19 patients with a limited diffusing capacity or history of pneumonitis received a novel high-dose regimen consisting of CCNU 15 mg/kg, VP 60 mg/kg and Cy 100 mg/kg. Twenty-nine patients (24%) had failed induction therapy and 35 (29%) had progressive HD within 1 year of initial chemotherapy. At 4 years actuarial survival was 52%, event-free survival was 48% and freedom from progression (FFP) was 62%. No significant differences were seen in survival data with the three preparatory regimens. Six patients died within 100 days of transplantation and 5 died at a later date of transplant-related complications. Secondary malignancies have developed in 6 patients, including myelodysplasia/leukemia in four patients and solid tumors in two patients. Regression analysis identified systemic symptoms at relapse, disseminated pulmonary or bone marrow disease at relapse and more than minimal disease at the time of transplantation as significant prognostic factors for overall and event-free survival and FFP. Patients with none of these factors enjoyed an 85% FFP at 4 years compared with 41% for patients with one or more unfavorable prognostic factors (P = .0001). Our results confirm the efficacy of high-dose therapy and autografting in recurrent or refractory HD. Although longer follow-up is necessary to address ultimate cure rates and toxicity, our data indicate that a desire to reduce late effects should drive future research efforts in favorable patients whereas new initiatives are needed for those with less favorable prognoses.

    View details for PubMedID 9028311

  • Primary radiotherapy is curative for CS I-E orbital malt lymphoma Eulau, S. M., Hildebrand, R., Warnke, R., Donaldson, S. S., Hoppe, R. T. PERGAMON-ELSEVIER SCIENCE LTD. 1997: 176
  • Hodgkin's disease: Complications of therapy and excess mortality 6th International Conference on Malignant Lymphoma Hoppe, R. T. OXFORD UNIV PRESS. 1997: 115–118

    Abstract

    The long-term survival of patients treated for Hodgkin's disease permits careful evaluation of long-term complications and excess mortality.Between 1960 and 1995, 2498 patients who were treated for Hodgkin's disease at Stanford University were evaluated. Survival, freedom from relapse, and important complications of therapy (cardiac disease and secondary cancers) were analyzed, and risk of mortality from all causes was calculated utilizing absolute excess risk calculations.The risk of death from Hodgkin's disease is 17% at 15 years of follow-up and increases only slightly thereafter. The risk of death from other causes is also 17% at 15 years, but increases sharply thereafter. The major causes of mortality (other than Hodgkin's disease) are secondary cancers and cardiac disease. Second cancers with significant increase in risk include leukemia (acute nonlymphocytic), non-Hodgkin's lymphoma, lung/pleural cancer, breast cancer, melanoma, soft tissue and bone sarcomas, stomach cancer, salivary gland tumors, thyroid cancer, and pancreatic cancer. The absolute excess risk of death from causes other than Hodgkin's disease increases during each five-year follow-up interval for at least 25 years. However, the absolute excess risk of death during similar follow-up periods is less for patients treated in more recent years (1980-1995) than in the prior treatment era (1962-1980).Mortality for causes other than Hodgkin's disease is important in the long-term follow-up of patients. Causes of death are often treatment related. Changes in treatment programs can reduce the long-term excess risk of death from complications of therapy.

    View details for Web of Science ID A1997XB82400025

    View details for PubMedID 9187444

  • Gastrointestinal cancer after treatment of Hodgkin's disease 37th Annual Scientific Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Birdwell, S. H., Hancock, S. L., Varghese, A., Cox, R. S., Hoppe, R. T. ELSEVIER SCIENCE INC. 1997: 67–73

    Abstract

    This study aimed to quantify the risk of gastrointestinal cancer following Hodgkin's disease treatment according to age at treatment, type of treatment, and anatomic sites.Cases were identified from the records of 2,441 patients treated for Hodgkin's disease between 1961 and 1994. Follow-up averaged 10.9 years, representing 26,590 person-years of observation. Relative risks (RR) for gastrointestinal cancer incidence and mortality were computed by comparison with expected annualized rates for a general population matched for age, sex, and race.Gastrointestinal cancers developed in 25 patients. The incidence RR was 2.5 [95% confidence interval (CI), 1.5-3.5] and mortality RR was 3.8 (CI, 2.4-4.7). Sites associated with significantly increased risks included the stomach [RR 7.3 (CI, 3.4-13.8)], small intestine [RR 11.6 (CI, 1.9-38.3)], and pancreas [RR 3.5 (CI, 1.1-8.5)]. Risk was significantly elevated after combined modality therapy, RR 3.9 (CI, 2.2-5.6). The risk after radiotherapy alone was 2.0 (CI, 1.0-3.4), not a statistically significant elevation. The RR for gastrointestinal cancer was greatest after treatment at young age and decreased with advancing age. It was significantly elevated within 10 years after treatment [RR 2.0 (CI, 1.1-3.5)] and increased further after 20 years [RR 6.1 (CI, 2.5-12.7)]. Risk assessed by attained age paralleled risk according to age at treatment. Fifteen cases of gastrointestinal cancers arose within the irradiation fields.Patients treated for Hodgkin's disease are at modestly increased risk for secondary gastrointestinal cancer, especially after combined modality therapy and treatment at a young age. Risk was highest more than 20 years after treatment, but was significantly elevated within 10 years. Gastrointestinal sites with increased risk included the stomach, pancreas, and small intestine.

    View details for Web of Science ID A1997WJ64600009

    View details for PubMedID 9054878

  • Over 20 Years of Progress in Radiation Oncology: Hodgkin's Disease. Seminars in radiation oncology Smitt, M. C., Buzydlowski, J., Hoppe, R. T. 1997; 7 (2): 127–34

    Abstract

    The Patterns of Care Study (PCS) surveys for Hodgkin's disease have documented important correlations between treatment processes and patient outcome. Nationwide improvements in radiotherapy for Hodgkin's disease since 1973, such as routine use of extended fields (subtotal lymphoid irradiation) in patients with early stage disease, individualized blocking, and treatment using linear accelerators, have resulted in greater freedom from relapse and overall survival for patients with stage I/II disease treated with radiotherapy alone. In addition, the introduction of computed tomography along with increased use of chemotherapy in high-risk patients has reduced the use of routine laparotomy and has improved outcome for patients with stage III disease. Overall survival for Hodgkin's disease in the national practice is excellent, reflecting the dissemination of complex treatment programs and radiation therapy technology to the oncologic community at large. Future studies of the national practice will be important in assessing the impact of managed care on workup and other facility practices, as well as evaluating the transfer of new approaches aimed at reducing treatment toxicities.

    View details for DOI 10.1053/SRAO00700127

    View details for PubMedID 10717207

  • Clinical stage IA (limited patch and plaque) mycosis fungoides - A long-term outcome analysis ARCHIVES OF DERMATOLOGY Kim, Y. H., Jensen, R. A., WATANABE, G. L., Varghese, A., Hoppe, R. T. 1996; 132 (11): 1309-1313

    Abstract

    To study the long-term results of treatment of patients with stage IA mycosis fungoides and analyze the factors related to disease progression and the effect of initial therapy on survival and freedom from relapse.A single-center, 32(1/2)-year, retrospective cohort analysis.Private referral medical center.One hundred twenty-two patients with clinical stage IA (T1, N0, M0) mycosis fungoides.Long-term actuarial survival and freedom-from-relapse results as calculated by the technique of Kaplan-Meier.The long-term (30-year) survival of patients with stage IA mycosis fungoides is similar to the expected survival of a race-, age-, and sex-matched control population. The median survival of this group has not been reached at 32(1/2)-years. Eleven patients (9%) who progressed to more advanced disease had a lower complete response rate to initial therapy than did other patients (36% vs 82%) and an older mean age than did other patients with T1 disease (61 vs 48 years, P < .05). Only 3 (2%) of 122 patients died of disease. Among stage IA patients who achieved a complete response, 25% are relapse free at 10 years. Patients who received total skin electron beam therapy (n = 34) had a more favorable freedom-from-relapse outcome than those treated with topical mechlorethamine hydrochloride (nitrogen mustard) (n = 73, P < .05). No significant difference was seen in the long-term survival between the 2 treatment groups.Patients with clinical stage IA mycosis fungoides treated at Stanford University do not have an altered life expectancy. Fewer than 10% progressed to more advanced stages and few died of disease. Although the response rate to total skin electron beam therapy was superior to that of topical mechlorethamine, the longterm survival results were similar. Topical mechlorethamine is a cost-effective and convenient therapy for patients with limited patch and plaque mycosis fungoides.

    View details for Web of Science ID A1996VT34900008

    View details for PubMedID 8915308

  • High-dose therapy and autologous bone marrow transplantation for relapsed/refractory Hodgkin's disease: The impact of involved field radiotherapy on patterns of failure and survival INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Poen, J. C., Hoppe, R. T., Horning, S. J. 1996; 36 (1): 3-12

    Abstract

    To assess the efficacy and toxicity of involved field (IF) radiotherapy in conjunction with high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) in relapsed or refractory Hodgkin's disease (HD).Between 1987 and 1994, 100 consecutive patients with relapsed or refractory HD were treated with high-dose carmustine, etoposide, and cyclophosphamide or fractionated total-body irradiation, high-dose etoposide, and cyclophosphamide before ABMT. In addition, 24 patients received IF radiotherapy as planned cytoreductive (n = 18) or consolidative (n = 6) therapy immediately before or following ABMT.With a median follow-up of 40 months (range: 18-88 months), 3-year actuarial rates of freedom from relapse (FFR), survival (S), and event-free survival (EFS) were 66%, 64%, and 57%, respectively. Thirty-three patients (33%) relapsed at a median of 8 months after ABMT. Only 2 of 33 relapses (6%) occurred beyond 18 months. By multivariate analyses, factors associated with recurrence were pleural disease (p = 0.02), multiple pulmonary nodules (p = 0.03), and a poor response to cytoreductive therapy (p = 0.001). A median IF radiotherapy dose of 30 Gy (range: 12.5-45 Gy) was given to 67 sites in the 24 patients. Local failure occurred within four irradiated sites (6%) in two patients (8%). In patients with relapse Stage I-III disease (n = 62), the use of IF radiotherapy was associated with an improved 3-year FFR (100% vs. 67%, p = 0.04) and a trend toward improved S (85 vs. 60%, p = 0.16). Among patients not previously irradiated (n = 39), IF radiotherapy was associated with an improved FFR (85 vs. 57%, p = 0.07) and S (93 vs. 55%, p = 0.02). Crude rates of treatment-related Grade 5 complications (including late events and second malignancies) were similar with or without IF radiotherapy (17 vs. 14%).In conjunction with high-dose therapy and autologous bone marrow transplantation, IF radiotherapy is well tolerated, effectively controls local and regional disease, and may improve survival in selected patients with relapsed or refractory Hodgkin's disease.

    View details for Web of Science ID A1996VH84000001

    View details for PubMedID 8823253

  • Long-Term Complications of Treatment and Causes of Mortality After Hodgkin's Disease. Seminars in radiation oncology Hancock, HOPPE 1996; 6 (3): 225-242

    Abstract

    The majority of newly diagnosed patients are expected to survive Hodgkin's disease because of effective therapies established during past 30 years. Long-term observations from large populations of treated patients have disclosed a variety of late effects of the disease and its therapy have contributed morbidity and excess mortality to Hodgkin's disease survivors. Secondary cancers have continued to accrue, and the risk relative to the general population has increased to 6.4 (95% confidence intervals: 5.5 to 7.3) in updated experience at Stanford University. Risks are significantly elevated for leukemia (primarily after chemotherapy regimens containing alkylating agents); non-Hodgkin's lymphoma; and tumors of the lung, breast, soft tissues, bone, stomach, pancreas, salivary gland, thyroid, and cutaneous melanoma. Early cardiovascular disease has also been observed and numerically exceeds second cancers as a cause of death in patients with early stage Hodgkin's disease (49 v 47 cases). Pulmonary dysfunction, thyroid dysfunction, infertility, psychosocial changes, gastrointestinal problems, soft-tissue changes, alterations in immunity, and risks for infection have also affected some treated patients. As these problems have been recognized, treatment approaches have been modified over the last 10 to 15 years, and early data suggest a decrease in some treatment sequellae.

    View details for PubMedID 10717180

  • Influence of preparatory regimen and source of hematopoietic cells on outcome of autotransplantation for non-Hodgkin's lymphoma. Biology of blood and marrow transplantation Stockerl-Goldstein, K. E., Horning, S. J., Negrin, R. S., Chao, N. J., Hu, W. W., Long, G. D., Hoppe, R. T., Amylon, M. D., BROWN, B. W., Wong, R. M., Blume, K. G. 1996; 2 (2): 76-85

    Abstract

    The use of high-dose chemotherapy with or without total-body irradiation (TBI) followed by autologous hematopoietic cell transplantation is associated with improved survival for relapsed or refractory non-Hodgkin's lymphoma (NHL). Previous reports comparing preparatory regimens with or without TBI followed by autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cell transplantation (PBPCT) for these patients did not demonstrate any survival difference between the different modalities. No randomized studies comparing survival for patients with NHL transplanted with radiochemotherapy vs. chemotherapy alone have been reported. We treated 221 patients with high-risk, relapsed or refractory NHL with either chemotherapy alone or radiochemotherapy followed by ABMT or PBPCT. The patients were assigned preparatory regimens in a non-randomized manner and this analysis was performed to evaluate differences in outcome with the two preparatory regimens. Actuarial five-year event-free survival (EFS) was similar in patients receiving fractionated total-body irradiation (FTBI) plus etoposide (VP-16) and cyclophosphamide (Cy) compared with chemotherapy alone consisting of carmustine (BCNU) plus identical doses of VP-16 and Cy (52% vs. 46%, p = 0.08). Overall survival (OS) favored radiochemotherapy (61%) compared with chemotherapy alone (53%, p = 0.02). The relapse rate was the same in both groups (41%), whereas the transplantation-related mortality (TRM) was similar in patients receiving chemotherapy alone and those receiving radiochemotherapy (13% vs. 7% respectively, p = 0.30). Proportional hazards analysis of significant variables including preparatory regimen found only the number of prior relapses to be predictive of EFS. Fewer number of prior relapses, radiochemotherapy and PBPCT were significant predictors of favorable OS. In additional analyses, the improved OS of the radiochemotherapy regimen was confirmed only for patients receiving ABMT but was not a significant predictor of outcome in patients transplanted with PBPCT. From these retrospective data we conclude: 1) PBPCT resulted in survival superior to that of ABMT; 2) the risk of relapse is similar with either preparatory regimen; 3) patients with fewer prior relapses enjoyed superior overall and event-free survival as well as fewer relapses; and 4) there were no significant differences in the two preparatory regimens when combined with PBPCT in relapsed or refractory NHL.

    View details for PubMedID 9118302

  • Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University JOURNAL OF CLINICAL ONCOLOGY MacManus, M. P., Hoppe, R. T. 1996; 14 (4): 1282-1290

    Abstract

    To evaluate retrospectively the results of radiotherapy for 177 patients with stage I (n = 73 [41%]) and II (n = 104 [59%]) follicular small cleaved-cell and follicular mixed small cleaved-cell and large-cell non-Hodgkin's lymphoma (NHL) treated in the Department of Radiation Oncology, Stanford University between 1961 and 1994.Histology was follicular small cleaved-cell in 101 (57%) cases and follicular mixed small cleaved-cell and large-cell in 76 (43%). Forty-five patients (25%) had staging laparotomy; 34 (19%) had extranodal involvement. All patients had received radiotherapy, either to one side of the diaphragm (involved or extended field) or to both sides (total lymphoid irradiation [TLI] or subtotal lymphoid irradiation [STLI]. Radiotherapy doses ranged from 35 to 50 Gy.The median follow-up duration was 7.7 years. The longest follow-up duration was 31 years. Actuarial survival rates at 5, 10, 15, and 20 years were 82%, 64%, 44%, and 35%, respectively. The median survival time was 13.8 years. At 5, 10, 15, and 20 years, 55%, 44%, 40%, and 37% of patients, respectively, were relapse-free. Only five of 47 patients who reached 10 years without relapse subsequently developed recurrence. Survival and freedom from relapse (FFR) were significantly worse for older patients. Relapse rates were lower following treatment on both sides of the diaphragm or staging laparotomy. Univariate analysis showed that youth and staging laparotomy were associated with significantly better survival and that FFR was better following treatment on both sides of the diaphragm or laparotomy.Radiotherapy remains the treatment of choice for early-stage low-grade follicular lymphomas. Patients who have remained free of disease for 10 years are unlikely to relapse.

    View details for Web of Science ID A1996UF06800031

    View details for PubMedID 8648385

  • Treatment of cutaneous T-Cell lymphoma with chimeric anti-CD4 monoclonal antibody BLOOD Knox, S., Hoppe, R. T., Maloney, D., Gibbs, I., Fowler, S., Marquez, C., Cornbleet, P. J., Levy, R. 1996; 87 (3): 893-899

    Abstract

    Chimeric anti-CD4 monoclonal antibody was administered intravenously as a single dose to eight patients with mycosis fungoides. The dose was escalated throughout the study between patients groups, and individual patients received 50, 100, or 200 mg per dose. Seven of eight patients responded to treatment with an average freedom from progression of 25 weeks (range, 6 to 52 weeks). The treatment was well tolerated, and there was no clinical evidence of immunosuppression. Following treatment, there was significant suppression of peripheral blood CD4 counts in all patients for 1 to 22+ weeks. Only one patient made a very low titer human antichimeric antibody response. All but two patients made primary antibody and T-cell proliferative responses to a foreign antigen administered 24 hours after antibody infusion. However, there was generally marked, but temporary suppression of T-cell proliferative responses in vitro to phytohemagglutinin (PHA), tetanus toxoid, and normal donor lymphocytes. We conclude that at the dose levels studied, this antibody (1) had clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) decreased T-cell proliferative responses in vitro, and (5) did not induce tolerance to a foreign antigen.

    View details for Web of Science ID A1996TT48400008

    View details for PubMedID 8562959

  • Hodgkin's disease - The role of radiation therapy in advanced disease 3rd International Symposium on Hodgkins Lymphoma Hoppe, R. T. KLUWER ACADEMIC PUBL. 1996: 99–103

    Abstract

    The success of radiation therapy (XRT) in the management of early-stage Hodgkin's disease (HD) has led to its use in a variety of programs for the management of advanced disease. This article includes discussion of these roles of radiation in advanced disease: 1) use of XRT as an adjuvant after chemotherapy; 2) use of XRT to convert patients who are 'partial responders' (PRs) after chemotherapy to 'complete responders' (CRs); 3) use of XRT as an integrated component of combined modality therapy; 4) use of XRT as a 'salvage' treatment after failure of primary chemotherapy; and 5) incorporation of XRT into programs of high-dose therapy with autologous stem cell (or marrow) rescue. 1) Randomized trials of adjuvant XRT after completion of chemotherapy in advanced disease have been conducted by the Southwest Oncology Group (SWOG), German HD Study Group, and the European Organization for the Research and Treatment of Cancer/Group Pierre Marie Curie (EORTC/ GPMC). The SWOG study shows improvements in disease-free survival, but not overall survival with the addition of XRT. The German Study Group trial was negative, but the number of patients reported in the abstract of the trial was too small to be conclusive. The EORTC/GPMC study has not been reported. 2) Both the SWOG and EORTC/GPMC trials treated "PRs' with XRT. Results in both show conversion to CR in > 80% of patients. Conversion to CR was most likely for patients with just minimal residual disease after chemotherapy. 3) Planned XRT in advanced disease (especially bulky sites) may permit reduction in chemotherapy doses (e.g., the Stanford V chemotherapy program) and maintain excellent outcome (freedom-from-progression > 80%). Reduction in total doses of chemotherapy as well as dose and extent of radiation should limit potential long-term toxicity. 4) Very selected patients with asymptomatic limited nodal relapse may be "salvaged' with XRT, but published reports include only a small number of patients and this should not be considered a standard approach. 5) XRT may be used as total body, total lymphoid, or local field in high-dose therapy programs. Since HD at relapse is still often a local-regional problem, local field irradiation is probably the most rational approach to use in this setting. Recent Stanford data show an improvement in outcome with the inclusion of local field treatment in these patients.

    View details for Web of Science ID A1996UZ46200019

    View details for PubMedID 8836419

  • Brief chemotherapy (Stanford V) and adjuvant radiotherapy for bulky or advanced Hodgkin's disease: An update 3rd International Symposium on Hodgkins Lymphoma Horning, S. J., Rosenberg, S. A., Hoppe, R. T. KLUWER ACADEMIC PUBL. 1996: 105–108

    Abstract

    From May 1989 to August 1995, 94 previously untreated patients with Hodgkin's disease stage II with bulky mediastinal involvement (n = 28) or stage III or IV (n = 66) received an abbreviated chemotherapy regimen, Stanford V, +/-radiotherapy (RT). Chemotherapy was given weekly for 12 weeks followed by consolidative RT to sites of initial bulky disease. With a median follow-up of 3 years, the actuarial 6-year survival is 93% and the freedom from progression is 89%. There have been no relapses or deaths among the 28 patients with stage II bulky mediastinal disease. Eight relapses and three deaths have occurred in the group of 66 patients with stage III-IV disease. The abbreviated chemotherapy regimen, Stanford V, in combination with RT is well tolerated and highly effective therapy for bulky, limited stage and advanced stage HD. Lower cumulative exposure to alkylating agents, doxorubicin, bleomycin and limited use of radiation is expected to improved the prospects for fertility and decrease the risks for second neoplasms and late cardiopulmonary toxicity.

    View details for Web of Science ID A1996UZ46200020

    View details for PubMedID 8836420

  • ELECTRON-BEAM TREATMENT FOR CUTANEOUS T-CELL LYMPHOMA HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA JONES, G. W., HOPPE, R. T., GLATSTEIN, E. 1995; 9 (5): 1057-&

    Abstract

    Total skin electron radiation has proven efficacy in treating MF. It is a complex technique that requires a dedicated radiation team, involving physicists, radiotherapists, and radiation oncologists. A center must treat a sufficiently high volume of patients to justify the development of TSE, with appropriate organization, time, and expense. The radiation team should be an integral part of a multidisciplinary clinical group, including medical oncologists, dermatologists, pathologists, and nurses. In these contexts, TSE has appropriately been developed in a limited number of centers. Cooperation between these centers is essential for further refinement of TSE techniques and for evolution of the role of TSE in the management of most patients with MF.

    View details for Web of Science ID A1995RX25600008

    View details for PubMedID 8522484

  • PROGNOSTIC FACTORS IN ERYTHRODERMIC MYCOSIS-FUNGOIDES AND THE SEZARY-SYNDROME ARCHIVES OF DERMATOLOGY Kim, Y. H., Bishop, K., Varghese, A., Hoppe, R. T. 1995; 131 (9): 1003-1008

    Abstract

    There are no large studies evaluating patients with erythrodermic mycosis fungoides and Sézary syndrome to determine the important prognostic factors that may influence survival. This is important since new treatment modalities have been proposed as superior to existing primary therapies. We performed a retrospective cohort study of 106 patients with erythrodermic mycosis fungoides and Sézary syndrome, followed up in the Stanford (Calif) Mycosis Fungoides Clinic, to define the important prognostic factors in this group.Patients younger than 65 years have a more favorable survival profile than those 65 years or older (P < .005). Longer duration of symptoms before diagnosis ( > or = 10 years) tends to be associated with more favorable prognosis (p = .055). Lymph node stage is significantly correlated with survival; patients with overall stage III disease have more favorable prognosis than those with stage IV disease (P < .001). Patients with circulating Sézary cells in their blood have a significantly worse prognosis than those without (P < .005). Patient sex or race had no significant effect on overall survival outcome. Three distinct prognostic groups were identified, "favorable," "intermediate," and "unfavorable," according to the number of unfavorable prognostic factors (P < .005). The median survival in each group is 10.2, 3.7, and 1.5 years, respectively.In patients with erythrodermic mycosis fungoides and Sézary syndrome, the important prognostic factors are patient age at presentation, the overall stage, and peripheral blood involvement. Survival varies widely, depending on these variables. These prognostic factors should be evaluated when analyzing survival and/or treatment efficacy data of these patients.

    View details for Web of Science ID A1995RU13500004

    View details for PubMedID 7661601

  • MULTIPLE COURSES OF HIGH-DOSE TOTAL SKIN ELECTRON-BEAM THERAPY IN THE MANAGEMENT OF MYCOSIS-FUNGOIDES INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Becker, M., Hoppe, R. T., Knox, S. J. 1995; 32 (5): 1445-1449

    Abstract

    A retrospective analysis was undertaken to determine the indications for, the efficacy of, and the long-term complications of two courses of total skin electron beam therapy for mycosis fungoides.A retrospective analysis of 15 patients with the pathologic diagnosis of mycosis fungoides treated in the Department of Radiation Oncology at Stanford University Medical Center between 1968 and 1990 was performed. All patients received two courses of high-dose electron beam therapy to the skin. The mean dose for the total skin treatment for the first course was 32.6 Gy and 23.4 Gy for the second course of treatment.Following the first course of total skin electron beam therapy, 11 of 15 had a complete response, with a mean duration of 11.6 months. All patients received adjuvant therapies between the first and second courses of high-dose total skin electron beam therapy. The mean interval between the first and the second courses of therapy was 41.3 months. Patients were restaged prior to commencement of their second course of high-dose total skin electron beam therapy, resulting in upstaging in six. The second course of therapy resulted in six complete responses and nine partial responses. Twelve of these patients have since died, 1 is lost to follow-up, and 2 are living with disease. The long-term side effects in the two living patients include pigmentation changes, alopecia, and diffuse xerosis.Delivery of two courses of total skin electron beam therapy is technically feasible, tolerable, and efficacious. The dose to the total skin was reduced for the second course of therapy in all cases. The criteria used to screen patients included initial good response to total skin electron treatment, long disease-free interval, exhaustion of other therapeutic modalities, and generalized skin involvement at relapse. Long-term toxicities were mild in severity and generally consisted of generalized xerosis, scattered telangiectasias, pigmentation changes, and partial alopecia.

    View details for Web of Science ID A1995RM87800020

    View details for PubMedID 7635786

  • PELVIC RELAPSE FOLLOWING SUBTOTAL LYMPHOID IRRADIATION IN EARLY-STAGE HODGKINS-DISEASE - AN ANALYSIS OF RISK, MANAGEMENT, AND OUTCOME INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Tate, D. J., Hoppe, R. T. 1995; 32 (4): 1239-1244

    Abstract

    To evaluate the time of onset, method of identification, management, and outcome of pelvic relapse following subtotal lymphoid irradiation (STLI) alone (mantle and paraaortic/spleen or splenic pedicle fields, excluding the pelvis) in supradiaphragmatic Stage I-II Hodgkin's disease.A retrospective analysis was performed of the initial, relapse, and regular follow-up evaluations of patients with pelvic relapse following STLI alone from 1968 to the present for supradiaphragmatic Stage I-II Hodgkin's disease after pathologic staging (PS-laparotomy staging) and clinical staging (CS-no laparotomy staging).Following staging, which included bipedal lymphangiography, 482 patients (408 PS and 74 CS), were treated with STLI alone for supradiaphragmatic Stage I-II Hodgkin's disease. The actuarial freedom from relapse at 20 years was 75% in PS patients and 81% in CS patients. The actuarial pelvic failure at 20 years was 7% for PS patients and 3% for CS patients. Of the 29 patients with pelvic relapse, 97% (28 of 29) occurred within 5 years of treatment, including 1 patient who progressed during initial treatment. Pelvic relapse was most commonly initially identified by abnormalities involving patient symptoms (62%), physical examination (55%), erythrocyte sedimentation rate (48%), and bipedal lymphangiogram and/or abdominal radiograph (38%). Relapse was limited to previously unirradiated sites in 17 patients (58%). In addition to pelvic lymph node disease, 3 patients (10%) had involvement of bone, and 4 patients (14%) had bone marrow involvement. Following relapse, all patients were treated with chemotherapy (MOP[P], MOP[P]/ABV[D], ABVD, or PAVe) and 19 of 29 patients received involved field consolidative irradiation. Twenty-one of 29 (72%) remained relapse free at the time of last follow-up evaluation, including 15 of 19 (79%) treated with combined therapy. Eight patients experienced a second relapse despite salvage therapy, and all eight expired with recurrent Hodgkin's disease. Two patients died of complications related to prior treatment. Therefore, the actuarial risk of death at 20 years associated with pelvic failure in the entire cohort of 482 patients was 2%.Pelvic relapse occurred in 7% of patients following STLI alone and was effectively diagnosed by regular follow-up, which included a combination of patient history, physical examination, and radiographic laboratory evaluation. Seventy-two percent of patients remained relapse free following salvage treatment, which included chemotherapy, resulting in an overall survival rate associated with pelvic control of 98%. This approach, therefore, spared the majority of patients the long-term risks associated with pelvic irradiation and/or chemotherapy, such as infertility, but maintained an excellent prognosis.

    View details for Web of Science ID A1995RL55500039

    View details for PubMedID 7607947

  • BRIEF CHEMOTHERAPY, STANFORD-V, AND ADJUVANT RADIOTHERAPY FOR BULKY OR ADVANCED-STAGE HODGKINS-DISEASE - A PRELIMINARY-REPORT JOURNAL OF CLINICAL ONCOLOGY Bartlett, N. L., Rosenberg, S. A., Hoppe, R. T., Hancock, S. L., Horning, S. J. 1995; 13 (5): 1080-1088

    Abstract

    Although survival rates have improved for patients with bulky and advanced-stage Hodgkin's disease (HD), current treatments entail substantial acute morbidity and risks for late effects such as infertility, second malignancies, and cardiopulmonary toxicities. A novel, brief chemotherapy regimen (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone [Stanford V]) was designed to shorten the duration of treatment, significantly reduce cumulative doses of alkylating agents, doxorubicin, and bleomycin, and maintain dose-intensity (DI). This brief chemotherapy was combined with radiation therapy (RT) to bulky disease sites.Since May 1989, 65 previously untreated patients were treated for stage II HD with bulky mediastinal involvement (n = 21) or for stage III or IV HD (n = 44). Patients received weekly chemotherapy for 12 weeks. Consolidative RT was given to the first 25 patients to sites of initial bulky disease or radiographic abnormalities that persisted after chemotherapy; in the remaining 40 patients, RT was limited to bulky disease (adenopathy > or = 5 cm and/or macroscopic splenic nodules defined by computed tomography [CT]).With a median follow-up period of 2 years, actuarial 3-year survival rate is 96% and failure-free survival (FFS) rate is 87%. The 3-year FFS rate is 100% for stage II patients with bulky mediastinal disease and 82% for patients with stage III to IV disease. There were no treatment-related deaths. In a preliminary analysis on a subset of patients, female and male fertility appears to be preserved.These preliminary results indicate that the Stanford V chemotherapy regimen with or without RT is well-tolerated and effective therapy for bulky, limited-stage, and advanced-stage HD. Less cumulative exposure to alkylating agents, doxorubicin, and bleomycin and limited use of radiation is expected to decrease risks for second neoplasms and late cardiopulmonary toxicity. Based on these results, the Stanford V chemotherapy with or without RT regimen deserves further study in the context of a randomized clinical trial.

    View details for Web of Science ID A1995QV95100006

    View details for PubMedID 7537796

  • CD8-POSITIVE TUMOR-INFILTRATING LYMPHOCYTES INFLUENCE THE LONG-TERM SURVIVAL OF PATIENTS WITH MYCOSIS-FUNGOIDES JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Hoppe, R. T., Medeiros, L. J., Warnke, R. A., Wood, G. S. 1995; 32 (3): 448-453

    Abstract

    Nonneoplastic mononuclear cells commonly infiltrate lesions of mycosis fungoides.We sought to determine the immunophenotypic characteristics of these cells and to determine whether the presence of CD8+ tumor-infiltrating lymphocytes has an impact on prognosis.Skin biopsy specimens from 78 patients were stained with immunopleroxidase techniques to determine their phenotypic characteristics. The proportion of CD8+ tumor-infiltrating lymphocytes was quantified and compared with stage of disease and survival rate.Patients with more limited T-stage disease tended to have a higher proportion of CD8+ cells in their skin biopsy specimens, compared with patients with more advanced T-stage disease. Within each T-stage patients with a larger proportion of CD8+ cells had a better survival rate than those with fewer CD8+ cells (p < 0.05 for T1 and T3). A multivariate analysis confirmed the importance of T stage (p = 0.0006), overall stage (p = 0.0112), and CD8 positivity (p = 0.0335) in this cohort of patients.CD8+ tumor-infiltrating lymphocytes in mycosis fungoides correlate with improved survival rate and may exert an antitumor effect rather than being mere bystander cells.

    View details for Web of Science ID A1995QJ45800006

    View details for PubMedID 7868714

  • PROGRESS IN THE TREATMENT OF HODGKINS-DISEASE IN THE UNITED-STATES, 1973 VERSUS 1983 - THE PATTERNS OF CARE STUDY CANCER HOPPE, R. T., HANLON, A. L., HANKS, G. E., OWEN, J. B. 1994; 74 (12): 3198–3203

    Abstract

    The prognosis for Hodgkin's disease patients has improved significantly since the early 1960s. The reasons for this improvement are multifactorial.In the Patterns of Care Study of the American College of Radiology, national surveys to examine process and outcome of patients treated for Hodgkin's disease in 1973 and 1983 were completed. Data were compared for patients who had Stage I-II Hodgkin's disease and who were treated with radiation therapy alone.Clinical characteristics of the patients in the two different treatment eras were similar. There were important differences in treatment parameters. In 1983 compared with 1973, there was more common use of a dedicated simulator, performance of routine port films, use of linear accelerators, use of individually shaped blocks, and treatment to extended fields. Adequacy of treatment fields also was judged superior in the 1983 study. There were improvements in survival and relapse-free survival for patients treated in 1983 versus 1973.Improvement in radiation therapy technique is associated with an improved outcome for patients treated for Hodgkin's disease. The national standards have improved during the time from 1973 to 1983.

    View details for DOI 10.1002/1097-0142(19941215)74:12<3198::AID-CNCR2820741219>3.0.CO;2-9

    View details for Web of Science ID A1994PW26800018

    View details for PubMedID 7982183

  • FRACTIONATED TOTAL-BODY IRRADIATION, ETOPOSIDE, AND CYCLOPHOSPHAMIDE PLUS AUTOGRAFTING IN HODGKINS-DISEASE AND NON-HODGKINS-LYMPHOMA JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Negrin, R. S., Chao, N. J., Long, G. D., Hoppe, R. T., Blume, K. G. 1994; 12 (12): 2552-2558

    Abstract

    High-dose etoposide was incorporated into a regimen of fractionated total-body irradiation (FTBI) and high-dose cyclophosphamide before autologous transplant with the goal to enhance the antitumor effect of the myeloablative regimen in poor-risk lymphoid malignancies.Ninety-six patients, 24 with recurrent or refractory Hodgkin's disease and 72 with poor-risk non-Hodgkin's lymphoma (NHL), were treated on this study. Cytoreduction with conventional therapy was attempted before administration of the preparatory regimen. The preparatory regimen consisted of 12 Gy total-body irradiation administered in 10 1.2-Gy fractions on day -8 through day -5, etoposide 60 mg/kg on day -4, and cyclophosphamide 100 mg/kg on day -2. Patients with NHL received bone marrow purged with a panel of monoclonal antibodies and complement on day 0, while patients with Hodgkin's disease received peripheral-blood stem cells alone or with unmanipulated bone marrow.The major morbidities of transplant were mucositis and skin toxicity. Eight patients (8.6%) died of regimen-related toxicities within 100 days of transplant. Engraftment was related to the rescue product; the median time to a neutrophil count more than 500/microL was 10 days for patients with Hodgkin's disease and 16 days for NHL patients. With a maximum follow-up duration of longer than 5 years, the 3-year actuarial survival rate is 57%. At 3 years, the actuarial freedom from progression (FFP) rate is 55% and the event-free survival rate is 47% for patients with Hodgkin's disease, while the respective figures for NHL patients are 60% and 53%. Among 32 patients with intermediate- and high-grade lymphoma transplanted subsequent to first relapse, 70% are free of lymphoma and 60% are event-free at > or = 3 years.The preparatory regimen consisting of FTBI, etoposide, and cyclophosphamide demonstrates relative efficacy in patients with Hodgkin's disease and NHL selected for high-dose therapy. Longer follow-up duration is needed to determine the rate of cure and to assess late complications. Major remaining challenges for high-dose therapy are a more inclusive strategy for all poor-risk patients and the need to reduce posttransplant relapses.

    View details for Web of Science ID A1994PV81100006

    View details for PubMedID 7989928

  • TREATMENT OF EARLY-STAGE GASTRIC LYMPHOMA JOURNAL OF SURGICAL ONCOLOGY BenYosef, R., Hoppe, R. T. 1994; 57 (2): 78-86

    Abstract

    The treatment of early-stage gastric lymphoma is controversial. This retrospective analysis reports on the outcome of 24 patients treated in our institution during the past 25 years. Fourteen patients had stage IEA, one patient had IEB, six patients IIEA1, and three patients had stage IIEA2 non-Hodgkin's lymphoma (NHL). Diffuse large cell intermediate-grade NHL was diagnosed in 17 patients, diffuse small cleaved cell in three patients, and diffuse mixed large and small cell lymphosarcoma, low-grade B-cell lymphoma, and unclassified lymphoma in one patient each. Fourteen patients underwent surgery, 21 had radiation therapy (XRT), and 10 patients received chemotherapy. Surgery + XRT were given to 7 patients, surgery + XRT + chemo and XRT alone were delivered to five patients each, and XRT + chemotherapy were employed in four patients. Surgery alone was the initial treatment in two patients and chemotherapy alone was given to one patient. Following treatment 22/24 achieved a complete response. During a mean follow-up period of 77.6 months (range 1-285), five patients relapsed. At 10 years, the actuarial survival of the 15 patients with stage I disease was 57.4% and for stage II it was 51.9% (Gehan P-value 0.33). Freedom from relapse (FFR) was 60.7% and 58.3%, respectively (P-value 0.56). No significant statistical differences in terms of survival and FFR were noted in patients treated with surgery, chemotherapy, or XRT. The outcome of patients treated with triple-modality therapy was similar to those treated with double-modality therapy and to patients treated with XRT alone. Gender, age, presenting symptoms, depth of tumor through the gastric wall, and stage were not statistically significant for prediction of either survival or FFR. Both surgery + XRT and chemotherapy + XRT are effective in the treatment of early-stage gastric disease. XRT alone is equally effective as two or three modality treatments in the subset of patients with early-stage gastric lymphoma. However, the low number of patients treated with various approaches over a long period precludes a firm conclusion. Until prospective randomized studies are initiated, management programs should be individually tailored.

    View details for Web of Science ID A1994PJ50900002

    View details for PubMedID 7934067

  • EXPRESSION OF CLASS-II MAJOR HISTOCOMPATIBILITY ANTIGENS BY KERATINOCYTES IN CUTANEOUS T-CELL LYMPHOMA INTERNATIONAL JOURNAL OF DERMATOLOGY Wood, G. S., Michie, S. A., Durden, F., Hoppe, R. T., Warnke, R. A. 1994; 33 (5): 346-350

    Abstract

    Expression of various class II MHC antigens by lesional keratinocytes may play an important role in the pathophysiology of a wide variety of human dermatoses including cutaneous T cell lymphoma (CTCL). Nevertheless, there is relatively little information available concerning the concurrent expression of HLA-DR, -DP, and -DQ class II MHC antigens in CTCL. Therefore, our aim in this study was to determine the prevalence, localization, extent, temporal sequence, and consistency of class II MHC antigen expression by lesional keratinocytes in CTCL.We used a semiquantitative immunohistologic analysis to analyze HLA-DR, -DP, and -DQ expression by lesional keratinocytes in 66 skin biopsies obtained from 39 patients with CTCL.Class II MHC antigen expression by keratinocytes was observed in 77% of cases. Expression was detected on the cytoplasmic membrane and within the cytoplasm. It varied among cases from focal to confluent. There was a hierarchy of antigen expression in terms of both extent and time course. HLA-DR was expressed first and most extensively, followed by HLA-DP and then HLA-DQ. Comparative studies of multiple serial or concurrent active lesions from 13 cases indicated that the overall pattern and extent of antigen expression was relatively constant within individual patients.There was no apparent correlation between class II MHC antigen expression and the clinical stage of disease, the type of CTCL skin lesion, or the overall density of the lesional T cell infiltrate. The hierarchy of keratinocyte class II MHC antigen expression observed in this study paralleled that noted in earlier studies of cultured keratinocytes exposed to recombinant interferon-gamma in vitro. This suggests that lesional cytokine levels may be the critical factor governing class II MHC antigen expression by lesional keratinocytes in CTCL.

    View details for Web of Science ID A1994NJ59200011

    View details for PubMedID 8039974

  • EFFECT OF TREATMENT FOR HODGKINS-DISEASE ON PULMONARY-FUNCTION - RESULTS OF A PROSPECTIVE-STUDY JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Adhikari, A., Rizk, N., Hoppe, R. T., Olshen, R. A. 1994; 12 (2): 297-305

    Abstract

    Because each of very different treatments for Hodgkin's disease (HD) may result in a high rate of cure, attention is currently focused on toxicity. This prospective study was designed to assess the effects of mediastinal irradiation and bleomycin chemotherapy on pulmonary function.Patients were treated from 1980 to 1990 on randomized controlled trials at Stanford University. Pulmonary function was tested before treatment (baseline), early after treatment (< 15 months), and more than 36 months posttherapy. Treatment options in the 145 patients were grouped as I (mediastinal radiotherapy), II (mediastinal radiotherapy plus bleomycin), and III (bleomycin) for analyses of variance (ANOVAs). A variety of regression models were used to predict early and late effects on pulmonary function.A decrease in forced vital capacity (FVC) and diffusing capacity (DLCO) in the first 15 months after treatment followed by recovery after 36 months was observed for most patients. Patients who received mediastinal radiotherapy (RT) had a more pronounced reduction in pulmonary function and less complete recovery. Overall, 3 or more years after treatment, 32% of group I patients, 37% of group II patients, and 19% of group III patients had FVC values less than 80% of predicted, while only 7% of patients had a DLCO less than 80% of predicted. Linear regression identified baseline measurement as the only significant predictor of change in percent predicted FVC or DLCO; patients with higher baseline values had greater decrements after therapy. Mantle RT was the only significant treatment variable, predictive of FVC and DLCO within 15 months and FVC at 36 or more months. No patient experienced pulmonary toxicity severe enough to require hospitalization.This prospective analysis of pulmonary function after treatment for HD showed that mediastinal RT was the only treatment variable that achieved statistical significance. Although there were no significant interactions between mediastinal RT and bleomycin or Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) chemotherapy, the patient numbers were small after correction for mediastinal mass size and drug regimen such that an effect could have been missed. The mild reduction in pulmonary function should be factored into the overall assessment of morbidity risk for each of the potentially curative treatments included in this study. As with all reports of late effects, these data should be interpreted with respect to the population tested, details of the treatment administered, methods of measurement, and length of follow-up.

    View details for Web of Science ID A1994MW70600012

    View details for PubMedID 7509383

  • EFFECT OF FILGRASTIM (G-CSF) IN HODGKINS-DISEASE PATIENTS TREATED WITH RADIATION INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Knox, S. J., Fowler, S., Marquez, C., Hoppe, R. T. 1994; 28 (2): 445-450

    Abstract

    To evaluate the effect of filgrastim (recombinant human G-CSF) on radiation-induced neutropenia in a well defined, homogenous patient population.Seven patients who were to receive large field subdiaphragmatic irradiation after thoracic "mantle" fields for treatment of Hodgkin's disease entered this study. They received daily subcutaneous (SC) injections of filgrastim during subdiaphragmatic irradiation. Total white blood cell (WBC) and absolute neutrophil cell (ANC) counts were measured and compared to a historical series of patients, and hematological toxicity was assessed. The endpoints of the study were nadir WBC and ANC counts and time to WBC and ANC recovery.Compared to the historical series, filgrastim significantly increased the WBC and ANC throughout the period of subdiaphragmatic irradiation. Nadir WBC (5.98 +/- 1.24/mm3) and ANC (4.71 +/- 1.07/mm3) in the Filgrastim group were approximately two times those of the historical series (3.32 +/- 1.06/mm3 and 2.39 +/- 0.97/mm3 respectively; p < 0.002). Nadir platelet counts were not affected by filgrastim therapy. Three of seven patients reported mild musculoskeletal pain, but there was no other apparent toxicity.Compared to the historical series, filgrastim therapy significantly increased WBC and ANC during extended field radiation therapy and was well tolerated. It may be clinically useful in other groups of patients who are likely to develop profound neutropenia during large field irradiation.

    View details for Web of Science ID A1994MP98100015

    View details for PubMedID 7506247

  • FRACTIONATED TOTAL-BODY IRRADIATION AND HIGH-DOSE ETOPOSIDE AS A PREPARATORY REGIMEN FOR BONE-MARROW TRANSPLANTATION FOR 99 PATIENTS WITH ACUTE-LEUKEMIA IN 1ST COMPLETE REMISSION BLOOD Snyder, D. S., Chao, N. J., Amylon, M. D., Taguchi, J., Long, G. D., Negrin, R. S., Nademanee, A. P., ODONNELL, M. R., Schmidt, G. M., Stein, A. S., Parker, P. M., Smith, E. P., Stepan, D. E., Molina, A., LIPSETT, J. A., Hoppe, R. T., Niland, J. C., Dagis, A. C., Wong, R. M., Forman, S. J., Blume, K. G. 1993; 82 (9): 2920-2928

    Abstract

    Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.

    View details for Web of Science ID A1993ME65700039

  • FACTORS AFFECTING LATE MORTALITY FROM HEART-DISEASE AFTER TREATMENT OF HODGKINS-DISEASE JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Hancock, S. L., TUCKER, M. A., Hoppe, R. T. 1993; 270 (16): 1949-1955

    Abstract

    To assess the risk of death from heart disease after Hodgkin's disease therapy.Retrospective study comparing treated patients with a matched general population.Referral center.A total of 2232 consecutive Hodgkin's disease patients treated from 1960 through 1991. Follow-up averaged 9.5 years.Relative risks (RRs), the ratio of the observed to the expected cases with 95% confidence intervals (CIs), chi tests for trends, and Kaplan-Meier actuarial risks.Of the 2232 patients, 88 (3.9%) died of heart disease, 55 from acute myocardial infarction and 33 from other cardiac diseases, including congestive heart failure, radiation pericarditis or pancarditis, cardiomyopathy, or valvular heart disease. The RR for cardiac death was 3.1 (CI, 2.4 to 3.7). Mediastinal radiation of 30 Gy or less (n = 385 patients) did not increase risk; above 30 Gy (n = 1830), RR was 3.5 (CI, 2.7 to 4.3). Blocking to limit cardiac exposure reduced the RR for other cardiac diseases from 5.3 (CI, 3.1 to 7.5) to 1.4 (CI, 0.6 to 2.9), but not acute myocardial infarction (RR, 3.7 vs 3.4). The RRs increased with duration after treatment (trend in acute myocardial infarction, P = .02; in other cardiac diseases, P = .004). The RR for acute myocardial infarction was highest after irradiation before 20 years of age and decreased with increasing age at treatment (P < .0001 for trend).Mediastinal irradiation for Hodgkin's disease increases the risk of subsequent death from heart disease. Risk increased with high mediastinal doses, minimal protective cardiac blocking, young age at irradiation, and increasing duration of follow-up.

    View details for Web of Science ID A1993MC51300026

    View details for PubMedID 8411552

  • CARDIAC DISEASE FOLLOWING TREATMENT OF HODGKINS-DISEASE IN CHILDREN AND ADOLESCENTS JOURNAL OF CLINICAL ONCOLOGY Hancock, S. L., Donaldson, S. S., Hoppe, R. T. 1993; 11 (7): 1208-1215

    Abstract

    Cardiac disease is second only to neoplastic disease as a cause of death after treatment for Hodgkin's disease. This study evaluates the risks of cardiac disease following treatment of Hodgkin's disease during childhood and adolescence.We reviewed records of 635 patients treated for Hodgkin's disease before 21 years of age at Stanford University between 1961 and 1991. Mean age was 15.4 years; mean follow-up duration was 10.3 years, representing 6,564 person-years of observation. Relative risks (RRs) of death from cardiac diseases were calculated by comparison with age-, sex-, and race-matched general population rates from United States decennial life-tables.Twelve patients have died of cardiac disease (RR, 29.6; 95% confidence interval [CI], 16.0 to 49.3), including seven deaths from acute myocardial infarction ([AMI] RR, 41.5; 95% CI, 18.1 to 82.1), three from valvular heart disease, and two from radiation pericarditis/pancarditis. Thus far, the risk of AMI death was comparable after radiation alone (RO) or after chemotherapy and radiation (CM) (RO-AMI RR, 52.2; 95% CI, 21.1 to 108.7; CM-AMI RR, 21.1; 95% CI, 0.0 to 104.4; P = .6). The risk for other cardiac death (CD) tended to be higher after combined treatment (RO-non-AMI RR, 7.4; 95% CI, 0.0 to 36.5; CM-non-AMI RR, 45.8; 95% CI, 14.4 to 110.6; P = .1). Deaths occurred 3 to 22 years after patients received 42 to 45 Gy to the mediastinum between 9 and 20 years of age. There have been no deaths among patients treated to lower mediastinal radiation doses or without mediastinal radiation. There are no clear trends in the latency of risk. One hundred six nonfatal abnormalities have also been diagnosed.Mediastinal radiation of 40 to 45 Gy increases the risk of death from coronary artery and other cardiac diseases. The risk increases within 5 years of irradiation. These observations support combined-modality, low-dose irradiation regimens in children and adolescents and suggest the need for careful cardiac screening of treated patients.

    View details for Web of Science ID A1993LL23300003

    View details for PubMedID 8315419

  • MR-IMAGING TO DETECT CHEST-WALL AND PLEURAL INVOLVEMENT IN PATIENTS WITH LYMPHOMA - EFFECT ON RADIATION-THERAPY PLANNING AMERICAN JOURNAL OF ROENTGENOLOGY CARLSEN, S. E., Bergin, C. J., Hoppe, R. T. 1993; 160 (6): 1191-1195

    Abstract

    The purpose of this study was to determine the influence that accurate MR detection of chest wall and pleural disease has on the type and extent of radiation therapy subsequently performed in patients with thoracic lymphoma.MR images and CT scans of the chests of 57 patients who had biopsy-proved lymphoma were retrospectively examined for evidence of involvement of the chest wall and pleura. For patients with thoracic lymphoma, we compared radiation portals and dosage designed by using information from MR images with portals and dosage designed by using information from chest radiographs and CT scans.Chest wall or pleural disease was detected in 22 of the 57 patients examined. Chest wall disease was identified on MR images in 20 patients (29 sites) and pleural disease in 14 patients (16 sites). Chest wall and pleural disease were identified on CT scans in seven and five patients, respectively. Of the 15 patients who received radiation therapy, three (20%) had treatment planning altered, either by increasing the area exposed to radiation or by increasing the radiation dose, because of findings noted only on MR images.Chest wall and pleural sites of disease that may be detected only on MR images can be important in designing appropriate radiation portals and dosage for patients who have chest lymphoma.

    View details for Web of Science ID A1993LW01300006

    View details for PubMedID 8498212

  • HODGKINS-DISEASE WITH BULKY MEDIASTINAL INVOLVEMENT - EFFECTIVE MANAGEMENT WITH COMBINED MODALITY THERAPY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS BEHAR, R. A., Horning, S. J., Hoppe, R. T. 1993; 25 (5): 771-776

    Abstract

    To assess results, complications, treatment techniques, and patterns of failure in patients with bulky mediastinal Hodgkin's disease treated with combined modality therapy.Between 1980 and 1988, 48 patients with Hodgkin's disease who had large mediastinal masses were treated at Stanford University. All patients were staged with clinical studies which included computed tomographic scans of the chest and bipedal lymphograms. Initially, 10 patients underwent staging laparotomy and splenectomy, subsequently all patients were staged by clinical criteria alone. Mediastinal mass ratios ranged from .35 to .85 (mean .46). The majority of patients had at least one site of extralymphatic extension (E-lesion) within the chest. Combined modality therapy included MOPP (prednisone deleted after mediastinal irradiation) in 15, ABVD in 14, and PAVe in 19 patients. All patients received mantle irradiation (mean dose 44 Gy) but only patients with abdominal disease received subdiaphragmatic irradiation.The actuarial survival and freedom from relapse were 84% and 88% at 9 years. There was an intrathoracic component of failure in all seven patients who either failed to achieve an initial complete response or who experienced a relapse after a complete response. Both patients who experienced a relapse after a complete response achieved durable second responses with subsequent chemotherapy. Two of five patients who failed to achieve an initial complete response were treated successfully with alternative chemotherapy.Routine combined modality therapy is the treatment of choice for patients with Hodgkin's disease who have large mediastinal masses.

    View details for Web of Science ID A1993KY32200002

    View details for PubMedID 7683016

  • MYCOSIS-FUNGOIDES - CLINICAL AND HISTOLOGIC FEATURES, STAGING, EVALUATION, AND APPROACH TO TREATMENT CA-A CANCER JOURNAL FOR CLINICIANS Abel, E. A., Wood, G. S., Hoppe, R. T. 1993; 43 (2): 93-115

    View details for Web of Science ID A1993KQ66700004

    View details for PubMedID 8439814

  • BREAST-CANCER AFTER TREATMENT OF HODGKINS-DISEASE JOURNAL OF THE NATIONAL CANCER INSTITUTE Hancock, S. L., TUCKER, M. A., Hoppe, R. T. 1993; 85 (1): 25-31

    Abstract

    Most studies of survivors of Hodgkin's disease have shown a low risk for subsequent breast cancer, even though much lower doses of radiation than those used for Hodgkin's disease have been shown to induce breast cancer in other settings.This study quantifies the risk of breast cancer following Hodgkin's disease treatment according to age at treatment and type of treatment.To evaluate the risk of breast cancer from irradiation, we reviewed records of 885 women treated for Hodgkin's disease between 1961 and 1990 (mean follow-up, 10 years). Risks for breast cancer incidence and mortality were calculated by comparison with expected rates for a general female population matched by age and race.Twenty-five patients have developed invasive breast cancer, yielding a relative risk (RR) of 4.1 (95% confidence interval [CI] = 2.5-5.7). An additional patient developed multifocal carcinoma in situ. Age at irradiation strongly influenced risk: RR was 136 for women treated before 15 years of age (95% CI = 34-371). RR declined with age at irradiation (P for trend < .0001), but the elevation remained statistically significant for subjects less than 30 years old at the time of irradiation (for those 15-24, RR = 19 [95% CI = 10.3-32]; for those 24-29, RR = 7 [95% CI = 3.2-14.4]). In women above 30 years of age, the risk was not elevated (RR = 0.7; 95% CI = 0.2-1.8). Risk of breast cancer increased significantly with time since treatment (P for trend < .0001). The RR was 2.0 (95% CI = 1.0-3.5) with follow-up under 15 years and 13.6 (95% CI = 7.9-18.2) with follow-up equal to or exceeding 15 years. The addition of mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy to irradiation increased the risk within the first 15 years. Most breast cancers (22 of 26) arose within or at the margin of the radiation field and were infiltrating ductal carcinomas. Stage distribution and outcome suggest that the increased incidence was not solely attributable to vigilant screening. RR of death from breast cancer was 5.1 (95% CI = 2.2-10.0).Women treated for Hodgkin's disease with radiation before 30 years of age are at markedly increased risk for breast cancer, with risk increasing dramatically more than 15 years after therapy.The high RR for development of breast cancer in women exposed to therapeutic radiation under 30 years of age raises important issues about optimal treatment strategies for patients with Hodgkin's disease, breast cancer, and other cancers.

    View details for Web of Science ID A1993KF02900011

    View details for PubMedID 8416252

  • PELVIC RELAPSE FOLLOWING SUBTOTAL LYMPHOID IRRADIATION IN EARLY-STAGE HODGKINS-DISEASE - AN ANALYSIS OF RISK, MANAGEMENT, AND OUTCOME TATE, D. J., HOPPE, R. T. PERGAMON-ELSEVIER SCIENCE LTD. 1993: 231
  • THE STANFORD EXPERIENCE WITH COMBINED PROCARBAZINE, ALKERAN AND VINBLASTINE (PAVE) AND RADIOTHERAPY FOR LOCALLY EXTENSIVE AND ADVANCED STAGE HODGKINS-DISEASE ANNALS OF ONCOLOGY Horning, S. J., Ang, P. T., Hoppe, R. T., Rosenberg, S. A. 1992; 3 (9): 747-754

    Abstract

    This report describes the efficacy and toxicity of PAVe (procarbazine, Alkeran, vinblastine) and irradiation (RT) in the management of 159 patients with locally extensive or advanced stage Hodgkin's disease (HD) at Stanford University. Patients received six courses of chemotherapy alternating with RT. The extent of RT and the schedule of treatment varied according to the stage of disease. About 2/3 of patients received PAVe/RT in the setting of prospective, randomized clinical trials. The rate of complete response was 93%. With a median follow-up of seven years (range 2-17), the 15 year actuarial freedom from progression (FFP) is 78% and overall survival is 75%. Ten-year FFP by stage is: 80% for locally extensive stage II, 90% for stage IIIA and 70% for stage IIIB. Excellent and equal results were attained with PAVe/RT vs. MOP(P) (mustard, Oncovin, procarbazine with or without prednisone)/RT in the randomized combined modality studies. Progression or recurrence was documented in 30 patients and was more common in irradiated sites. PAVe was well tolerated acutely. There were no treatment related fatalities. Twenty-three (14%) patients were admitted to the hospital for neutropenic fever. Five second malignancies have occurred after PAVe/RT only: one myelodysplastic syndrome, one acute myelogenous leukemia, one non-Hodgkin's lymphoma and two solid tumors including a case of non-small cell lung cancer and an in situ carcinoma of the cervix. Three patients died from myocardial infarction several years after the completion of treatment. These mature data show that PAVe/RT is effective and well-tolerated therapy for locally extensive stage II and IIIA/B HD.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1992JW88200021

    View details for PubMedID 1450064

  • SECONDARY LEUKEMIA AND MYELODYSPLASTIC SYNDROME AFTER TREATMENT FOR HODGKINS-DISEASE 2ND INTERNATIONAL COURSE - LEUKEMIA 1992 : RECENT PROGRESS IN BIOLOGY AND CLINICAL RESEARCH IN ADULT LEUKEMIA Hoppe, R. T. NATURE PUBLISHING GROUP. 1992: 155–157

    View details for Web of Science ID A1992KA43200043

    View details for PubMedID 1434819

  • THE MANAGEMENT OF HODGKINS-DISEASE IN RELAPSE AFTER PRIMARY RADIATION-THERAPY EUROPEAN JOURNAL OF CANCER Hoppe, R. T. 1992; 28A (11): 1920-1922

    Abstract

    Approximately 20-25% of patients with stage I-II Hodgkin's disease treated initially with irradiation alone will experience a relapse of disease. Restaging at the time of relapse provides a useful prognostic indicator and may help in the selection of salvage therapy. Systemic treatment is indicated in nearly all patients. In the Stanford experience, 109 patients who relapsed were treated with MOPP (or MOPP-like chemotherapy) with or without local irradiation. The actuarial 10-year survival and freedom from second relapse were both 57%. Important prognostic factors included 'relapse stage' (IA vs. II-IIIA vs. I-IIIB or IV) and type of salvage therapy (combined modality vs. chemotherapy alone). Important issues in management of these patients include the selection of chemotherapy agents, whether to incorporate localised irradiation, and the use of even more aggressive salvage treatment programs, such as autologous bone marrow transplantation, in selected patients with a very poor prognosis.

    View details for Web of Science ID A1992JK74700036

    View details for PubMedID 1389536

  • COMBINED-MODALITY THERAPY FOR THE TREATMENT OF HODGKINS-DISEASE 26TH ANNUAL SAN FRANCISCO CANCER SYMP Hoppe, R. T. KARGER. 1992: 172–180

    View details for Web of Science ID A1992BW35T00015

    View details for PubMedID 1511919

  • METASTATIC CARCINOMA IN LYMPH-NODES SIMULATING SYNCYTIAL VARIANT OF NODULAR SCLEROSING HODGKINS-DISEASE AMERICAN JOURNAL OF CLINICAL PATHOLOGY Bacchi, C. E., Dorfman, R. F., Hoppe, R. T., Chan, J. K., Warnke, R. A. 1991; 96 (5): 589-593

    Abstract

    The authors report the histories of two patients with undifferentiated carcinoma metastatic to lymph nodes simulating the "syncytial variant" of nodular sclerosing Hodgkin's disease. One of the patients initially was treated for Hodgkin's disease, but the clinical evolution was more typical of carcinoma. Both lesions were characterized histologically by noncohesive aggregates of large neoplastic cells with abundant eosinophilic cytoplasm and conspicuous nucleoli. Although cells compatible with diagnostic Reed-Sternberg cells were identified in an "appropriate" cellular background in both patients, the diagnosis of carcinoma was supported by intense cytokeratin immunoreactivity. Subtle histologic clues that should suggest the possibility of metastatic carcinoma in a patient whose morphologic data suggests the syncytial variant of nodular sclerosing Hodgkin's disease include sinus infiltration, phagocytosis of neutrophils by tumor cells, marked nuclear anaplasia, and the presence of spindle-shaped tumor cells.

    View details for Web of Science ID A1991GN54700007

    View details for PubMedID 1719796

  • ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR HIGH-RISK ACUTE LYMPHOBLASTIC-LEUKEMIA DURING 1ST COMPLETE REMISSION BLOOD Chao, N. J., Forman, S. J., Schmidt, G. M., Snyder, D. S., Amylon, M. D., KONRAD, P. N., Nademanee, A. P., ODONNELL, M. R., Parker, P. M., Stein, A. S., Smith, E., Wong, R. M., Hoppe, R. T., Blume, K. G. 1991; 78 (8): 1923-1927
  • THE MANAGEMENT OF MYCOSIS-FUNGOIDES AT STANFORD - STANDARD AND INNOVATIVE TREATMENT PROGRAMS 2ND VICENZA INTERNATIONAL WORKSHOP OF HEMATOLOGY : NEW INSIGHTS IN LYMPHOMAS Hoppe, R. T. STOCKTON PRESS. 1991: 46–48

    View details for Web of Science ID A1991GH79800011

    View details for PubMedID 1716337

  • TOTAL LYMPHOID IRRADIATION FOR TREATMENT OF INTRACTABLE CARDIAC ALLOGRAFT-REJECTION JOURNAL OF HEART AND LUNG TRANSPLANTATION Hunt, S. A., Strober, S., Hoppe, R. T., Stinson, E. B. 1991; 10 (2): 211-216

    Abstract

    The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for "salvage" therapy of cardiac allograft rejection unresponsive to conventional therapy.

    View details for Web of Science ID A1991FE16600002

    View details for PubMedID 2031918

  • OBSERVATIONS ON THE EFFECT OF CHIMERIC ANTI-CD4 MONOCLONAL-ANTIBODY IN PATIENTS WITH MYCOSIS-FUNGOIDES BLOOD Knox, S. J., Levy, R., Hodgkinson, S., Bell, R., Brown, S., Wood, G. S., Hoppe, R., Abel, E. A., Steinman, L., Berger, R. G., Gaiser, C., Young, G., Bindl, J., Hanham, A., Reichert, T. 1991; 77 (1): 20-30

    Abstract

    Chimeric (murine/human) anti-CD4 monoclonal antibody was infused into seven patients with mycosis fungoides. Successive patients received doses of 10, 20, 40, and 80 mg of antibody twice a week for 3 consecutive weeks. All patients had some clinical improvement, but responses were of relatively short duration. Serum levels of chimeric antibody varied as a function of dose. At the 80-mg dose level, antibody was readily observed in biopsied skin lesions. Although there was coating by antibody of most CD4 positive cells in the blood, there was no significant depletion of CD4 positive cells. Low-level antibody responses against the mouse Ig variable region and human Ig allotypic constant region determinants were observed in several patients, but none were of clinical significance. All but two patients made primary antibody and T-cell proliferative responses to a simultaneously administered foreign protein test antigen. However, there was marked suppression of the mixed lymphocyte reaction. We conclude that at the dose levels studied, a chimeric anti-CD4 monoclonal antibody (1) had some clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) had immediate immunosuppressive effects; and (5) did not induce tolerance to a co-injected antigen.

    View details for Web of Science ID A1991EQ04100003

    View details for PubMedID 1984796

  • THE STANFORD EXPERIENCE WITH HIGH-DOSE ETOPOSIDE CYTOREDUCTIVE REGIMENS AND AUTOLOGOUS BONE-MARROW TRANSPLANTATION IN HODGKINS-DISEASE AND NON-HODGKINS-LYMPHOMA - PRELIMINARY DATA ANNALS OF ONCOLOGY Horning, S. J., Chao, N. J., Negrin, R. S., Hoppe, R. T., Kwak, L. W., Long, G. D., STALLBAUM, B., OCONNOR, P., Blume, K. G. 1991; 2: 47-50

    Abstract

    Seventy-seven Hodgkin's disease and non-Hodgkin's lymphoma (NHL) patients received high-dose etoposide in combination with cyclophosphamide and either fractionated total body irradiation (TBI) (n = 28) or carmustine (n = 49) prior to autologous bone marrow transplantation. Marrow from NHL patients was purged in vitro with a panel of monoclonal B- and T-cell antibodies and complement. Six toxic deaths (8%) occurred, all in patients who received carmustine. With a median follow-up of 1 year, 57 patients are alive and free from progressive disease. The 1-year actuarial survival and freedom from progression are 85 and 73% in fractionated TBI/etoposide/cyclophosphamide-treated patients and 79 and 72% in carmustine/etoposide/cyclophosphamide-treated patients. Forty-five of these patients participated in prospective trials for which eligibility criteria were (1) less than 25% curability with conventional therapy; (2) achievement of minimal disease state with conventional therapy; and (3) transplantation early in the course of disease. One-year actuarial survival for 18 patients with relapsed Hodgkin's disease is 80% and for 21 relapsed intermediate and high-grade NHL patients, 70%. One NHL Burkitt's patient was transplanted on a protocol for high-risk intermediate and high-grade NHL in first remission. Five patients with follicular mixed or small cleaved NHL were also transplanted in first remission.

    View details for Web of Science ID A1991EV30000010

    View details for PubMedID 2043498

  • TOTAL SKIN ELECTRON-BEAM THERAPY IN THE MANAGEMENT OF MYCOSIS-FUNGOIDES 25TH ANNUAL SAN FRANCISCO CANCER SYMP : THE ROLE OF HIGH ENERGY ELECTRONS IN THE TREATMENT OF CANCER Hoppe, R. T. KARGER. 1991: 80–89

    View details for Web of Science ID A1991BT33D00007

    View details for PubMedID 1908426

  • RADIATION-THERAPY IN THE MANAGEMENT OF HODGKINS-DISEASE SEMINARS IN ONCOLOGY Hoppe, R. T. 1990; 17 (6): 704-715

    View details for Web of Science ID A1990EM75000007

    View details for PubMedID 2251517

  • DISCORDANT EXPRESSION OF ANTIGENS BETWEEN INTRAEPIDERMAL AND INTRADERMAL T-CELLS IN MYCOSIS-FUNGOIDES AMERICAN JOURNAL OF PATHOLOGY Michie, S. A., Abel, E. A., Hoppe, R. T., Warnke, R. A., Wood, G. S. 1990; 137 (6): 1447-1451

    Abstract

    Using immunohistochemical methods, the authors studied the expression of pan-T- and majority-T-cell antigens (CD5, CD2, CD3, TCR-beta, CD7) and T-cell subset antigens (CD4, CD8) in cutaneous T cells in mycosis fungoides (MF) (177 biopsies from 124 patients) and a variety of inflammatory lesions (45 biopsies from 45 patients). The authors detected the absence of pan-T- or majority-T-cell antigens, or of both T-cell subset antigens, from T cells in the epidermis but not the dermis in 15 MF biopsies (8%) from 11 MF patients (9%), but in none of the inflammatory skin lesions. The opposite picture, characterized by lack of antigen expression by the dermal T cells only, was not seen in any of the MF or inflammatory lesions. The absence of antigen expression by epidermal but not dermal T cells, which the authors have termed antigen discordance, was most prevalent for CD5, CD7, and TCR-beta, each being discordant in 6% to 7% of MF cases or patients tested. Among the MF biopsies showing antigen discordance, 14 of 15 biospies (93%) from 10 of 11 patients (91%) were discordant for two or more antigens. Antigen discordance was not an artifact of treatment, because none of the patients showing discordance was receiving treatment at the time of their initial discordant biopsy. The discordance was the only immunophenotypic abnormality detected in 8 of 15 (53%) of the discordant MF biopsies. Thus, this antigen discordance was an important diagnostic feature that allowed the immunophenotypic distinction of MF from a variety of inflammatory skin lesions.

    View details for Web of Science ID A1990EP24300020

    View details for PubMedID 2260631

  • Mycosis fungoides and the Sézary syndrome: pathology, staging, and treatment. Current problems in cancer Hoppe, R. T., Wood, G. S., Abel, E. A. 1990; 14 (6): 293-371

    Abstract

    Mycosis fungoides and the Sézary syndrome are forms of cutaneous T-cell lymphoma. Mycosis fungoides is an uncommon disease: only about 500 new cases are diagnosed in the United States annually. The median age of onset is 55 years and there is a 2:1 male predominance. The etiology of mycosis fungoides is unknown. Although occupational exposures have been implicated, case control studies fail to support this hypothesis. Mycosis fungoides is typified by cutaneous plaques which may evolve into tumors over the course of time. It is often preceded by a lengthy pre-mycotic phase prior to the time of definitive diagnosis. In its earliest diagnostic phase, there may only be slightly scaling patches with a limited distribution. Indurated lesions evolve into plaques, which may become more generalized in their distribution. As the severity of skin involvement increases, there is an increasing likelihood of spread to extracutaneous sites. The pathology of this disease is marked by involvement of the epidermis (Pautrier microabscesses). Immunologic studies characterize these cells as belonging to the helper T-cell subset. Genotypic analysis demonstrates monoclonal rearrangements of the T-cell receptors of the infiltrating cells. The staging system for mycosis fungoides considers the extent of skin involvement, presence of lymph node or visceral disease, and detection of abnormal cells in the peripheral blood. Patients with disease limited to the skin (90% of newly diagnosed cases) are treated best with topical or cutaneous therapies. Common modalities include psoralen photochemotherapy (PUVA), topical chemotherapy (nitrogen mustard) and total skin electron beam therapy. Both topical nitrogen mustard and electron beam therapy have good initial response rates (73% and 100%) and may achieve long-term disease-free survival, especially in patients with initially limited disease. Even if the response is incomplete or relapse occurs, substantial and very important palliation is generally achieved with topical therapy. Recurrent or resistant cutaneous disease will require the use of sequential topical treatment. The median survival time of patients who present with disease limited to the skin is greater than 10 years, and many deaths in this group are from intercurrent causes, especially in patients with limited or generalized plaque disease. If cutaneous tumors are present, the majority of these patients will eventually die from disease-related causes. The prognosis of patients who develop extracutaneous disease is exceedingly poor (median survival time, approximately 1 year).(ABSTRACT TRUNCATED AT 400 WORDS)

    View details for PubMedID 2245651

  • RADIATION-THERAPY IN THE MANAGEMENT OF BULKY MEDIASTINAL HODGKINS-DISEASE 71ST ANNUAL MEETING OF THE AMERICAN RADIUM SOC BEHAR, R. A., Hoppe, R. T. WILEY-LISS. 1990: 75–79

    Abstract

    From July 1981 to July 1985, 20 patients with bulky mediastinal Hodgkin's Disease (maximum mediastinal width divided by the maximum intrathoracic diameter for a mediastinal mass ratio (MMR) greater than 0.33 were treated at Stanford University with definitive radiation therapy alone. The majority of these patients were selected to receive radiation therapy because they had the more favorable characteristics of minimal extralymphatic involvement, mediastinal masses that were superior and central in location, and a MMR less than or equal to 0.50. All 20 patients were laparotomy staged, and 17 received some radiation to the mantle before laparotomy. Seventeen patients had pathologic stage (PS) II disease (13 PS IIA, 4 PS IIB), two had PS IIISA, and one had PS IB. Eleven patients (55%) had extralymphatic involvement. All patients were irradiated to the mantle field using a shrinking field technique (mediastinal dose, 4400 to 5500 cGy, mean 4990 cGy). After completion of the mantle, all patients with good clinical responses received infradiaphragmatic radiation. Treatment complications included two cases of mild radiation pneumonitis, five of hypothyroidism, five of localized Herpes zoster, one of amenorrhea, one of non-Hodgkin's lymphoma, and one of sepsis. Four patients relapsed. All had an intrathoracic component to their failure. All four patients were salvaged with MOP(P) chemotherapy and are currently alive and free of disease. For the entire group, the actuarial freedom from relapse is 80% at 7 years and the survival is 100%. Median follow-up time is 67 months. The authors conclude that radiation therapy alone is effective in the management of selected patients with Hodgkin's disease who have extensive mediastinal involvement, even when the MMR exceeds 1/3.

    View details for Web of Science ID A1990DK33100014

    View details for PubMedID 2354412

  • LEU-8/CD7 ANTIGEN EXPRESSION BY CD3+ T-CELLS - COMPARATIVE-ANALYSIS OF SKIN AND BLOOD IN MYCOSIS-FUNGOIDES SEZARY-SYNDROME RELATIVE TO NORMAL BLOOD VALUES JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Wood, G. S., Hong, S. R., Sasaki, D. T., Abel, E. A., Hoppe, R. T., Warnke, R. A., Morhenn, V. B. 1990; 22 (4): 602-607

    Abstract

    Deficiencies of Leu-8 and CD7 antigens are exhibited by CD3+ T cells in the skin lesions of most patients with mycosis fungoides/Sézary syndrome. To determine whether these antigenic abnormalities are limited to involved skin, we studied Leu-8/CD7 expression in 21 skin lesions of mycosis fungoides/Sézary syndrome obtained from 16 patients and compared them with their peripheral blood leukocytes obtained concurrently. There was no correlation between Leu-8/CD7 values in skin lesions versus blood. Blood values were relatively uniform; most patients had 50% or greater of CD3+, Leu-8+ T cells and CD3+, CD7+ T cells. In contrast, skin values were highly heterogeneous; most patients lacked expression of Leu-8 or CD7 by the majority of lesional CD3+ T cells. Furthermore, Leu-8/CD7 antigen deficiency was present in lesional skin in one patient with mycosis fungoides but not in her concurrently sampled pityriasis lichenoides chronica or blood. These findings suggest that Leu-8/CD7 antigen deficiencies in skin lesions of mycosis fungoides/Sézary syndrome do not represent generalized antigenic abnormalities of CD3+ T cells in other body compartments and that within the skin, these deficiencies are disease specific within individual patients with more than one dermatosis. Comparative peripheral blood immunophenotyping of the patients with mycosis fungoides/Sézary syndrome and of the control subjects indicated that the control ranges of CD3+/Leu-8+ and CD3+/CD7+ T cells (33% or greater) extend lower than reported previously (60% or greater) and suggested that leukemic involvement in patients with mycosis fungoides/Sézary syndrome may correlate with percentages of CD3+, Leu8+ and/or CD3+, CD7+ T cells that fall below the revised control range.

    View details for Web of Science ID A1990CW00600008

    View details for PubMedID 1690762

  • PROGNOSTIC FACTORS FOR PATIENTS RELAPSING AFTER RADIOTHERAPY FOR EARLY-STAGE HODGKINS-DISEASE JOURNAL OF CLINICAL ONCOLOGY Roach, M., Brophy, N., Cox, R., Varghese, A., Hoppe, R. T. 1990; 8 (4): 623-629

    Abstract

    Prognostic factors were analyzed retrospectively in 109 patients who relapsed after treatment with radiation only for Hodgkin's disease. Factors analyzed included initial stage, age, time to first relapse, histology, sex, extent of initial irradiation, sites of relapse, relapse stage (RS), average relative dose intensity (ARDI) of chemotherapy, and type of salvage therapy. Ninety-three percent of the patients received either standard or modified mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). With a median follow-up of 8.3 years, the actuarial survival and freedom from second relapse (FF2ndR) was 57% at 10 years. The extent of disease at the time of relapse, or so-called RS was found to be the single most important prognostic factor. Nearly 90% of patients with RS IA or IEA (favorable group) were disease free, and nearly 60% of patients with RS IIA, IIEA, or IIIA (intermediate group) were disease free compared with only 34% of patients with B symptoms or stage IV disease (unfavorable group). In a subset analysis, the use of combined modality therapy (CMT) was associated with an improved FF2ndR and survival in patients from the intermediate and unfavorable relapse groups. Age greater than 50 years was associated with an increased risk of second relapse and a lower survival. The other factors analyzed appeared to be of no independent prognostic value.

    View details for Web of Science ID A1990CW56500009

    View details for PubMedID 2313331

  • Bone marrow transplantation for hematologic malignancies: the Stanford experience. Clinical transplants Chao, N. J., Amylon, M. D., Long, G. D., Negrin, R. S., Hoppe, R. T., Horning, S. J., Blume, K. G. 1990: 157-163

    Abstract

    Allogeneic and autologous BMTs are highly effective and successful treatment modalities for selected patients. Use of BMT earlier in the course of disease yields better results when compared to patients with more advanced disease. Recent advances such as use of cloned growth factors, cytokines, etc..., will continue to contribute to lessen morbidity and mortality. Finally, as investigators understand, prevent, and treat expected side effects from BMTs, the patients' burden in terms of physical, psychological, and financial costs should lessen substantially.

    View details for PubMedID 2103141

  • CUTANEOUS LYMPHOID HYPERPLASIA - IMMUNOLOGICAL CHARACTERISTICS AND ASSESSMENT OF CRITERIA RECENTLY PROPOSED AS DIAGNOSTIC OF MALIGNANT-LYMPHOMA JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Medeiros, L. J., Picker, L. J., Abel, E. A., Hu, C. H., Hoppe, R. T., Warnke, R. A., Wood, G. S. 1989; 21 (5): 929-942

    Abstract

    Fifteen cases of cutaneous lymphoid hyperplasia were studied immunohistologically with a large panel of monoclonal antibodies to determine their immunoarchitectural composition and to determine whether immunologic criteria recently proposed to identify lymphoma ever occur in benign skin lesions. All lesions were composed of T cells, polytypic B cells, macrophages, and Langerhans cells. Although only six cases containing lymphoid follicles were recognized in routinely stained sections, an additional five were identified in immunoperoxidase-stained sections. These follicles were of both the primary and secondary types and contained dendritic reticulum cell networks. The immunophenotypic features of these follicles were similar to those of reactive follicles in lymphoid organs and contrasted sharply with those reported previously for follicular lymphomas. Helper T cells were predominant in 11 cases. With regard to proposed criteria for T cell lymphoma, we did not detect loss of pan T cell antigens CD2, CD3, CD5, or BF-1, nor did we find populations of T cells with abnormal co-expression or loss of subset antigens such as CD4-8- or CD4+8+. Two cases in which relatively sparse infiltrates were present, however, were moderately CD7-deficient. This finding suggests that the CD7 criterion for cutaneous T cell neoplasia be modified in this situation. As observed previously, Leu-8 antigen deficiency was a common, nonspecific finding. With regard to proposed criteria for B cell lymphoma, we did not detect populations of B cells that were immunoglobulin-negative, nor did we observe preferential loss of one or more B-lineage antigens, histocompatibility complex-associated antigens, or lymphocyte function-associated antigens. We also did not identify any CD5+ B cells. On the basis of a comparison of our current data with prior studies of cutaneous lymphomas, we conclude that the immunologic findings recently proposed as general criteria for the differentiation of lymphoma from lymphoid hyperplasia are, in fact, applicable to cutaneous lymphoid lesions.

    View details for Web of Science ID A1989AX59500005

    View details for PubMedID 2808829

  • OUTCOME OF THE ACUTE GLOMERULAR INJURY IN PROLIFERATIVE LUPUS NEPHRITIS JOURNAL OF CLINICAL INVESTIGATION Chagnac, A., Kiberd, B. A., Farinas, M. C., Strober, S., Sibley, R. K., Hoppe, R., Myers, B. D. 1989; 84 (3): 922-930

    Abstract

    Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

    View details for Web of Science ID A1989AN25900027

    View details for PubMedID 2760219

  • Acquired immune tolerance to cadaveric renal allografts. A study of three patients treated with total lymphoid irradiation. New England journal of medicine Strober, S., Dhillon, M., Schubert, M., Holm, B., Engleman, E., Benike, C., Hoppe, R., Sibley, R., Myburgh, J. A., Collins, G. 1989; 321 (1): 28-33

    View details for PubMedID 2525231

  • ACQUIRED IMMUNE TOLERANCE TO CADAVERIC RENAL-ALLOGRAFTS - A STUDY OF 3 PATIENTS TREATED WITH TOTAL LYMPHOID IRRADIATION NEW ENGLAND JOURNAL OF MEDICINE Strober, S., Dhillon, M., Schubert, M., Holm, B., Engleman, E., Benike, C., Hoppe, R., Sibley, R., Myburgh, J. A., Collins, G., Levin, B. 1989; 321 (1): 28-33
  • EXPRESSION OF T-CELL RECEPTOR ANTIGENS IN MYCOSIS-FUNGOIDES AND INFLAMMATORY SKIN-LESIONS JOURNAL OF INVESTIGATIVE DERMATOLOGY Michie, S. A., Abel, E. A., Hoppe, R. T., Warnke, R. A., Wood, G. S. 1989; 93 (1): 116-120

    Abstract

    Using immunohistologic methods, we studied the expression of the T-cell receptor (TCR)-associated antigens CD3, TCR-beta, and TCR-delta by cutaneous T cells in mycosis fungoides (MF) (36 patients) and a variety of inflammatory diseases (16 patients). Most T cells in the inflammatory diseases and patch/plaque mycosis fungoides expressed the immunophenotype characteristic of the vast majority of mature peripheral T cells: CD3+ TCR-beta+ TCR-delta-. In contrast, abnormal CD3/TCR-beta antigen expression was seen in 3 of 6 cases (50%) of tumor stage mycosis fungoides. Furthermore, we were able to document its evolution from the normal pattern present in earlier patch/plaque lesions of the two cases in which serial biopsies were available for study. Divergence of epidermal versus dermal CD3/TCR-beta antigen expression was seen in 2 of 34 (6%) of biopsies of patch/plaque mycosis fungoides but not in inflammatory controls. The TCR-delta+ cells were generally rare regardless of diagnosis. We conclude that inflammatory skin diseases and most patch/plaque mycosis fungoides are typically composed of T lymphocytes that resemble mature peripheral T cells in regard to their expression of TCR-associated antigens. In contrast, aberrant patterns of TCR-associated antigen expression can be seen in tumor stage MF, and, more rarely in patch/plaque MF.

    View details for Web of Science ID A1989AG41600020

    View details for PubMedID 2473133

  • CLONAL REARRANGEMENTS OF IMMUNOGLOBULIN GENES AND PROGRESSION TO B-CELL LYMPHOMA IN CUTANEOUS LYMPHOID HYPERPLASIA AMERICAN JOURNAL OF PATHOLOGY Wood, G. S., Ngan, B. Y., Tung, R., HOFFMAN, T. E., Abel, E. A., Hoppe, R. T., Warnke, R. A., Cleary, M. L., Sklar, J. 1989; 135 (1): 13-19

    Abstract

    Cutaneous lymphoid hyperplasia (CLH) is a disorder characterized by the development of one or more skin lesions containing dense lymphoid infiltrates that exhibit the histopathologic features of a benign, reactive process. Nevertheless, some cases have been associated with the subsequent development of clinically overt lymphomas. This suggests that monoclonal populations may exist in some cases of CLH and that these cases may represent a subset more likely to evolve into lymphoma. To determine if such a subset of CLH can be distinguished, Southern blot analysis of DNA was used to study the immunogenotypic features of lesions from 14 patients with clinical, histopathologic, and immunopathologic findings characteristic of CLH. Five cases exhibited detectable clonal rearrangements of immunoglobulin genes. Furthermore, one of these five cases evolved into overt diffuse large cell lymphoma of B cell lineage during a 2-year follow-up of recurrent disease at the original cutaneous site. The immunoglobulin gene rearrangements of this lymphoma were identical to those of the prior CLH lesion. There was no evidence of detectable t(14;18) chromosomal translocations or clonal rearrangements of the beta gene of the T cell receptor in any case. It was concluded that CLH can be divided into two subsets based on the presence or absence of a clonal B cell population, and that overt lymphoma can arise from the former subset and contain the same B cell clone identified in the pre-existent CLH lesion.

    View details for Web of Science ID A1989AP09500003

    View details for PubMedID 2774056

  • THE MANAGEMENT OF BULKY MEDIASTINAL HODGKINS-DISEASE HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA Hoppe, R. T. 1989; 3 (2): 265-276

    Abstract

    Patients with Hodgkin's disease who have a large mediastinal mass present a challenge to the oncologist. Individualized therapy is often a key consideration for the management of these patients. Careful clinical staging is essential to develop the most effective treatment plan. The majority of these patients may be treated most effectively with combined modality therapy; however, a carefully selected group may be treated successfully with irradiation alone. Close follow-up is helpful to detect early relapse or manage complications of therapy.

    View details for Web of Science ID A1989U560600007

    View details for PubMedID 2663827

  • CHARACTERIZATION OF SPLENIC STRUCTURE IN HODGKIN DISEASE BY USING NARROW-BAND FILTRATION OF BACKSCATTERED ULTRASOUND AMERICAN JOURNAL OF ROENTGENOLOGY Friedman, P. A., Sommer, F. G., Chen, H. S., RACHLIN, D. J., Hoppe, R. 1989; 152 (6): 1197-1203

    Abstract

    A preliminary study was performed to evaluate the effectiveness of narrow-band filtration of backscattered ultrasound for the detection of splenic involvement in patients with Hodgkin disease. Regions of interest were identified in the spleens of 14 normal volunteers and eight Hodgkin disease patients before staging laparotomy. An analysis of the narrow-band-filtered waveforms showed that the mean amplitudes of the filtered ultrasonic signals received correlated with the presence of extensive splenic involvement with Hodgkin disease (defined as more than four grossly visible nodules on cut section) (p = .0004). Conversely, mean amplitudes of unfiltered ultrasonic backscatter, employed in conventional sonographic imaging, did not correlate with splenic involvement (p = .5). Phantom studies were performed to develop a tissue model for the observed phenomena; images of the phantoms and of the involved and uninvolved spleens were made by using techniques involving narrow-band filtration of backscattered ultrasound. Our results indicate that narrow-band-filtered sonography holds promise for detecting lymphomatous involvement of the spleen, although larger studies, with equipment allowing real-time implementation of narrow-band filtering, are needed.

    View details for Web of Science ID A1989U668700011

    View details for PubMedID 2655388

  • SMALL LYMPHOCYTIC LYMPHOMA JOURNAL OF CLINICAL ONCOLOGY Morrison, W. H., Hoppe, R. T., Weiss, L. M., Picozzi, V. J., Horning, S. J. 1989; 7 (5): 598-606

    Abstract

    The clinical course of 54 patients with small lymphocytic lymphoma (SL) was reviewed. The majority of patients had disseminated lymphoma at the time of diagnosis; 14 patients (26%) presented with Ann Arbor stage I and II disease. Five- and 10-year survival for all patients was 76% and 49%. The only clinicopathologic features identified that predicted a shortened survival were the presence or absence of systemic (B) symptoms (15% v 63% at 10 years, P = .01) and a diffuse rather than pseudofollicular nodal architecture (47% v 87% at 10 years, P = .04). Initial bone marrow involvement was not an adverse prognostic factor for patients who presented with stage III and IV disease. Ten patients developed a marked lymphocytosis consistent with progression to a leukemic phase (chronic lymphocytic leukemia [CLL]). These ten patients had a median initial lymphocyte count of 2,790, compared with 1,580 for those patients who did not progress to CLL (P = .0001). Developing CLL did not adversely affect survival (P = .48). Thirty-seven patients were treated with various combinations of radiation and chemotherapy; 17 patients received no initial therapy. Ten-year freedom from relapse (FFR) for stage I and II patients treated with irradiation was 80% and 62%; FFR for stage III and IV treated patients was 11%. Despite the marked differences in FFR, no statistically significant difference in survival could be demonstrated between the various stages. Selected patients with advanced SL received no initial therapy; these patients had a 10-year survival that was not statistically different from the immediately treated stage III and IV patients. Patients with stage I and II SL should be treated with irradiation; prolonged FFR and possibly cure of the disease can be achieved in these patients.

    View details for Web of Science ID A1989U451300008

    View details for PubMedID 2651577

  • DETECTION OF CLONAL T-CELL RECEPTOR GENE REARRANGEMENTS IN THE PERIPHERAL-BLOOD OF PATIENTS WITH MYCOSIS-FUNGOIDES SEZARY SYNDROME JOURNAL OF INVESTIGATIVE DERMATOLOGY Weiss, L. M., Wood, G. S., Hu, E., Abel, E. A., Hoppe, R. T., Sklar, J. 1989; 92 (4): 601-604

    Abstract

    Involvement of the peripheral blood in mycosis fungoides/Sezary syndrome (MF/SS) has a significant impact upon prognosis, but it is often difficult to distinguish circulating cells of MF/SS from atypical reactive lymphocytes. We compared the standard morphologic method of identifying leukemic cells, the Sezary preparation, to a genotypic method using Southern blot analysis of T-cell receptor gene rearrangements in concurrent blood samples. We studied 26 MF/SS patients, five of them in remission, together with five controls from cases of various non-MF/SS skin diseases. Six of 26 MF/SS patients had morphologically atypical circulating leukocytes (3%, 4%, 5%, 14%, 16%, 19%). Seven of 26 MF/SS patients had clonal T-cell receptor gene rearrangements, including the four patients with the greatest percentages of atypical cells and three patients lacking atypical cells. Six of seven patients had skin disease at the time of sampling, including three with erythroderma, two with generalized thick plaques, and one with generalized patches, while one patient was in clinical remission. All five controls lacked morphologic and genotypic evidence of atypical or clonal T-cells. Relative to genotyping, in our series the Sezary preparation was less sensitive and less specific. There were three apparent false negative results in the Sezary preparations, and two potential false positive (patients with 3% and 4% atypical leukocytes); however, there was agreement between the two techniques in most cases. We conclude that gene rearrangement studies may provide an effective test with which to assess the peripheral blood of MF/SS patients.

    View details for Web of Science ID A1989U234000009

    View details for PubMedID 2784818

  • PROGNOSTIC INDICATORS OF LAPAROTOMY FINDINGS IN CLINICAL STAGE-I-II SUPRADIAPHRAGMATIC HODGKINS-DISEASE JOURNAL OF CLINICAL ONCOLOGY LEIBENHAUT, M. H., Hoppe, R. T., Efron, B., Halpern, J., Nelsen, T., Rosenberg, S. A. 1989; 7 (1): 81-91

    Abstract

    Between July 1968 and July 1986, 915 patients with clinical stage (CS) I and II Hodgkin's disease limited to sites above the diaphragm underwent laparotomy and splenectomy at Stanford University. Fifteen percent were CS I, of whom 76% had cervical/supraclavicular disease, 13% axillary disease, and 9% mediastinal presentations. CS I patients were more likely to be male, were significantly older, and were significantly less likely to have nodular sclerosis (NS) histology than CS II patients. Twenty percent of CS I patients and 30% of CS II patients were pathologically upstaged. No CS I patients were upstaged to pathological stage (PS) IV. Univariate and multivariate analyses of presenting clinical characteristics were performed to predict staging laparotomy findings. CS I women, CS I patients with mediastinal-only disease, and CS I men with either lymphocyte predominance or interfollicular histologies were at low risk for having disease below the diaphragm (5%) or requiring chemotherapy (0%). CS II women who were less than 27 years old and had only two or three sites of disease were also at low risk for upstaging (9%) or requiring chemotherapy (2%). Mixed cellularity histology and male gender were associated with increased risk for subdiaphragmatic disease and require laparotomy; the presence of systemic symptoms was not correlated with laparotomy findings. These results confirm the importance of performing staging laparotomy for the majority of patients who present with supradiaphragmatic Hodgkin's disease if treatment programs are based on the presence and extent of subdiaphragmatic disease. Selected subgroups are at low risk for subdiaphragmatic disease and might be spared laparotomy if they are treated with mantle, paraaortic, and splenic irradiation.

    View details for Web of Science ID A1989R711000012

    View details for PubMedID 2909669

  • EFFECTS OF IRRADIATION ON THE HUMAN IMMUNE-SYSTEM 23RD ANNUAL SAN FRANCISCO CANCER SYMP : RADIATION TOLERANCE OF NORMAL TISSUES Hoppe, R. T. KARGER. 1989: 140–149

    View details for Web of Science ID A1989BP94U00010

    View details for PubMedID 2697651

  • NON-HODGKIN LYMPHOMA - INFLUENCE OF LYMPHOGRAPHY, CT, AND BONE-MARROW BIOPSY ON STAGING AND MANAGEMENT RADIOLOGY Pond, G. D., Castellino, R. A., Horning, S., Hoppe, R. T. 1989; 170 (1): 159-164

    Abstract

    This prospective study assesses the contribution of lymphography (LAG), abdominal-pelvic computed tomography (CT), and bone marrow biopsy to the staging and management of 168 consecutive cases of newly diagnosed non-Hodgkin lymphoma (NHL). LAG and/or CT influenced Ann Arbor clinical stage (CS) in 39 patients (23%) and Ann Arbor pathologic stage (PS) in 23 patients (14%) by detection of clinically inapparent retroperitoneal adenopathy and/or extranodal disease. LAG findings raised the CS in eight patients and the PS in six of the eight by showing adenopathy when the CT results were negative. By depicting extranodal disease, CT resulted in the CS being raised in an additional ten patients and the PS in six of the ten. Of the diagnostic tests assessed, bone marrow biopsy and/or cytology had the greatest influence on staging. Clinical staging that included LAG/CT resulted in the identification of only 30 patients with CS IV disease, whereas an additional 53 CS I through CS III patients had their disease stage raised to PS IV due to positive bone marrow biopsy/cytology results. However, 42 of the 53 patients already had advanced (CS III) disease. Initial case management was influenced by LAG, CT, or bone marrow biopsy/cytology results in 27 of 168 patients. LAG/CT results influenced management in 20 of 27 cases, while bone marrow biopsy/cytology results caused initial management changes in only seven of the 27 cases.

    View details for Web of Science ID A1989R388600036

    View details for PubMedID 2909090

  • Current Stanford clinical trials for Hodgkin's disease. Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer Hoppe, R. T., Horning, S. J., Hancock, S. L., Rosenberg, S. A. 1989; 117: 182-190

    View details for PubMedID 2690227

  • VINBLASTINE, BLEOMYCIN, AND METHOTREXATE - AN EFFECTIVE ADJUVANT IN FAVORABLE HODGKINS-DISEASE JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Hoppe, R. T., Hancock, S. L., Rosenberg, S. A. 1988; 6 (12): 1822-1831

    Abstract

    Sixty-seven patients with favorable pathologic stage (PS) I and IIA or B or IIIA Hodgkin's disease were randomized to receive subtotal or total lymphoid irradiation (STLI/TLI) alone or involved field irradiation (IF) plus six cycles of a novel adjuvant chemotherapy containing vinblastine, bleomycin, and methotrexate (VBM). With a follow-up from 6 to 72 months (median, 37 months), the actuarial freedom-from-progressive disease (FFP) at 5 years is 70% after STLI/TLI and 95% after IF plus VBM. One death has occurred in the irradiation-only treatment group. The data for IF plus VBM are significantly superior to previous actuarial results at 5 years using IF alone (FFP = 35%, P less than .00001) and compare favorably with prior results with IF plus nitrogen mustard, vincristine, procarbazine, +/- prednisone (MOP[P]) chemotherapy (FFP = 80% at 5 years, P = .10). VBM is well tolerated with greater than 90% of calculated doses delivered. As anticipated, VBM has had relatively little adverse effect on male or female fertility. Selected pulmonary functions are reduced early after IF plus VBM to a greater degree than with irradiation of the mediastinum alone, but the differences are modest. Based upon our current numbers and follow-up, we can be 90% confident that VBM as an adjuvant to irradiation in favorable Hodgkin's disease is as effective, or even superior, to MOP(P) chemotherapy. Because of its lesser toxicity, adjuvant VBM may have a broader role in the management of Hodgkin's disease.

    View details for Web of Science ID A1988R308000006

    View details for PubMedID 2462025

  • BENIGN AND MALIGNANT FORMS OF ERYTHRODERMA - CUTANEOUS IMMUNOPHENOTYPIC CHARACTERISTICS JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Abel, E. A., LINDAE, M. L., Hoppe, R. T., Wood, G. S. 1988; 19 (6): 1089-1095

    Abstract

    In order to determine if immunohistologic features are useful in distinguishing benign from malignant types of erythroderma, we studied the immunophenotype of lesional T cells in 20 patients (8 mycosis fungoides/Sézary syndrome, 12 benign) and found them to be generally similar. In all cases, the majority of T cells were Leu-1+, Leu-4+, and Leu-5+, as is typical of mature T cells. Although in most cases a majority of Leu-3+ (helper/phenotype) T cells were present, in 2 there was a majority of the Leu-2+ (cytotoxic/suppressor) subset and in 12 others, a significant minority (20%-40%) of these cells. Low percentages of Leu-2+ cells (less than or equal to 10%), resulting in high Leu-3+/Leu-2+ ratios, did not distinguish benign from malignant erythroderma. Leu-8 antigen deficiency was common in both mycosis fungoides/Sézary syndrome and benign cases (62% vs 75%, respectively). In contrast, Leu-9 antigen deficiency was present in only one patient in each group. The lack of combined Leu-8/9 antigen deficiency in our patients may be due to a heavy inflammatory T cell component, obscuring the antigen deficiencies seen in most nonerythrodermic mycosis fungoides cases. We conclude that immunophenotypic studies with the use of the current antibody panel show many similarities between benign and malignant forms of erythroderma, as well as some minor differences that may prove diagnostically useful if corroborated by future studies.

    View details for Web of Science ID A1988R205700014

    View details for PubMedID 2974461

  • THE CONTEMPORARY MANAGEMENT OF HODGKIN DISEASE RADIOLOGY Hoppe, R. T. 1988; 169 (2): 297-304

    View details for Web of Science ID A1988Q497400001

    View details for PubMedID 3140289

  • COMBINED MODALITY THERAPY FOR STAGE-I-II LARGE CELL LYMPHOMA INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Prestidge, B. R., Horning, S. J., Hoppe, R. T. 1988; 15 (3): 633-639

    Abstract

    Between January 1978 and December 1986, 94 patients with Stage I-II large cell lymphoma were evaluated at Stanford University Medical Center and treated with a combination of chemotherapy (CTX) and irradiation (XRT). The predominant histology was diffuse large cell (78), followed by immunoblastic (7), follicular large cell (6), and diffuse mixed small and large cell lymphoma (3). Twenty-three patients had Stage I and 71 had Stage II disease. Fifty-one had extranodal involvement (13 IE, 38 IIE), and 11 had B symptoms (2 IB, 9 IIB). Lymphoma was supradiaphragmatic in 58 patients, infradiaphragmatic in 21, and only in extranodal sites in 15. Patients received either involved (81) or extended (13) field XRT with a median dose of 40 Gy and combination CTX with 2 to 9 cycles (median 6) of either CHOP (68), M-BACOD (8), C-MOPP (8), MACOP-B (4), or other (6). Seventy-two patients remain with no evidence of disease, 21 are dead with disease, and one suffered an intercurrent death. Among the 19 patients who relapsed, there were six failures within the XRT field only, two within and outside the XRT field, and 11 outside of the XRT fields only. Actuarial survival and freedom from relapse (FFR) for the entire population were 74% and 72% at 5-years, respectively (33 month median follow-up). Stage I patients achieved 81% survival and 78% FFR, and Stage II patients had 72% survival and 70% FFR. In univariate and multivariate analyses, a favorable outcome was associated with the CTX-XRT-CTX sequence of therapy (p = 0.001), low LDH (p = 0.01), and small tumor bulk (p = 0.04). There were no relapses or deaths among the 21 patients receiving the "sandwich" sequence (CTX-XRT-CTX) of therapy. This series may serve as a comparison with single modality treatment programs for localized large cell lymphoma using either XRT or CTX alone.

    View details for Web of Science ID A1988Q175500017

    View details for PubMedID 3138215

  • INTERCURRENT DEATH AFTER HODGKIN DISEASE THERAPY IN RADIOTHERAPY AND ADJUVANT MOPP TRIALS ANNALS OF INTERNAL MEDICINE Hancock, S. L., Hoppe, R. T., Horning, S. J., Rosenberg, S. A. 1988; 109 (3): 183-189

    Abstract

    To assess long-term differences in mortality associated with initial Hodgkin disease therapy.Retrospective review of patients treated in prospectively randomized clinical trials.Three hundred twenty-six patients with pathologic stage I, II, or III, A or B Hodgkin disease treated between 1967 and 1980 with median follow-up exceeding 14 years.Patients at the same stage of disease were randomized to receive radiation alone (167 patients) or radiation followed by 6 cycles of mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone (MOPP) chemotherapy (159 patients) with additional therapy for progression or recurrence.No significant differences between treatment regimens for actuarial survival, intercurrent disease, or Hodgkin disease mortality were seen. Thirty-three patients who received radiation alone and 30 patients who received adjuvant chemotherapy died without evident Hodgkin disease. Death was caused by second neoplasms in 28 patients (relative risk, 2.35; 95% CI, 1.46 to 3.24). Six patients developed acute myelogenous leukemia or a myeloproliferative disorder after treatment including MOPP. Chemotherapy exposure varied among the 8 patients with lung cancers, 6 with gastrointestinal and 3 with other adenocarcinomas, 3 with sarcomas, 1 with diffuse large cell lymphoma, and 1 with melanoma. Acute myocardial infarction caused 9 of 17 cardiovascular disease deaths with 5 occurring in patients between the ages of 33 and 43. Nonetheless, the risk for acute myocardial infarction was not clearly increased (relative risk, 0.86; 95% CI, 0.42 to 1.57). Fifteen patients died from infection: 5, opportunistic; 5, asplenic sepsis; and 5, other pneumonias. Two patients died in accidents, and 1 died from radiation pneumonitis.Adjuvant MOPP chemotherapy improved freedom from relapse without significant survival benefit or impairment. Leukemogenesis was the only lethal complication associated with MOPP. Survivors of Hodgkin disease had an increased risk for death from a second neoplasm, but no apparent increased risk for death from acute myocardial infarction.

    View details for Web of Science ID A1988P606500005

    View details for PubMedID 3291657

  • TREATMENT OF LUPUS NEPHRITIS WITH TOTAL LYMPHOID IRRADIATION - OBSERVATIONS DURING A 12-79-MONTH FOLLOW-UP ARTHRITIS AND RHEUMATISM Strober, S., Farinas, M. C., Field, E. H., SOLOVERA, J. J., Kiberd, B. A., Myers, B. D., Hoppe, R. T. 1988; 31 (7): 850-858

    Abstract

    Seventeen patients with intractable lupus nephritis and nephrotic syndrome were treated with total lymphoid irradiation. Statistically significant improvement in mean renal disease and serologic activity parameters occurred within 3 months and persisted for at least 3 years. Although there was a marked reduction of T helper cell numbers and function after total lymphoid irradiation, recovery of these parameters was not associated with a return of disease activity. Risks of sterility, severe infections, and hematologic malignancy appeared to be lower than with alkylating agents.

    View details for Web of Science ID A1988P390700005

    View details for PubMedID 3260782

  • CLINICAL AND IMMUNOLOGICAL STUDIES OF CADAVERIC RENAL-TRANSPLANT RECIPIENTS GIVEN TOTAL-LYMPHOID IRRADIATION AND MAINTAINED ON LOW-DOSE PREDNISONE TRANSPLANTATION Saper, V., Chow, D., ENGLEMAN, E. D., Hoppe, R. T., Levin, B., Collins, G., Strober, S. 1988; 45 (3): 540-546

    Abstract

    Twenty-five recipients of cadaveric renal transplants were given total lymphoid irradiation (TLI), perioperative antithymocyte globulin, and low-dose prednisone as the sole maintenance immunosuppressive drug. Nine patients were diabetic, and follow-up was between 19 and 37 months. One-year graft and patient survival was 76% and 87%, respectively, Serious complications included four deaths from cardiovascular disorders, and two deaths from viral infections. Studies of peripheral blood T cell subsets showed a prolonged reduction in the absolute number of helper (Leu-3+) cells, and a rapid recovery of cytotoxic/suppressor (Leu-2+) cells. Analysis of the latter subset, using the monoclonal antibody 9.3, showed that the ratio of suppressor/cytotoxic cells was approximately 10:1. The normal ratio is 1:1. The mean mixed leukocyte reaction remained below 30% of the pre-TLI value for 6 months, and approached 80% at two years. Similar kinetics were observed in the proliferative response to mitogens. The results show that maintenance immunosuppressive drug therapy can be reduced after TLI as compared with conventional drug regimens that use prednisone in combination with cyclosporine and/or azathioprine.

    View details for Web of Science ID A1988M597000008

    View details for PubMedID 3279577

  • POIKILODERMATOUS MYCOSIS-FUNGOIDES AND ATROPHIC LARGE-PLAQUE PARA-PSORIASIS EXHIBIT SIMILAR ABNORMALITIES OF T-CELL ANTIGEN EXPRESSION ARCHIVES OF DERMATOLOGY LINDAE, M. L., Abel, E. A., Hoppe, R. T., Wood, G. S. 1988; 124 (3): 366-372

    Abstract

    We studied the immunohistologic findings of skin biopsy specimens from 21 patients with poikiloderma (14 with mycosis fungoides [MF] and seven with atrophic large-plaque parapsoriasis [ALPP]). Both types of poikiloderma were similar with regard to T-cell antigen expression. In each case, most T cells expressed the CD4+ (helper/inducer) phenotype and lacked Leu-8 antigen. T cells were also deficient in Leu-9 antigen in most cases (MF, 11/14 [79%]; ALPP, 4/7 [57%]). These T-cell antigen deficiencies are similar to those described previously in various types of MF and indicate that such deficiencies are common in minimally infiltrated, patch-stage MF lesions. Because combined Leu-8/Leu-9 antigen deficiencies are uncommon in inflammatory skin diseases, our findings are consistent with the view that ALPP is an early form of MF, as had been suggested previously by results of clinicopathologic studies.

    View details for Web of Science ID A1988M426400016

    View details for PubMedID 3257858

  • NODULAR AND DIFFUSE TYPES OF LYMPHOCYTE PREDOMINANCE HODGKINS-DISEASE NEW ENGLAND JOURNAL OF MEDICINE Regula, D. P., Hoppe, R. T., Weiss, L. M. 1988; 318 (4): 214-219

    Abstract

    The nodular form of lymphocyte predominance Hodgkin's disease has been shown to be immunophenotypically distinct from the histologically diffuse form and from other types of Hodgkin's disease. We undertook a clinicopathological study of 73 cases to determine whether any clinical differences between the nodular and diffuse subtypes could be discerned. Patients with the diffuse form (n = 41) tended to have a course similar to that of other types of Hodgkin's disease; there were few relapses and only two deaths due to Hodgkin's disease. In contrast, patients with the nodular form (n = 32) had significantly more relapses, which were independent of stage or treatment and equally distributed up to 10 years after initial therapy. Despite the frequent relapses, patients with the nodular form had an indolent course, and there was only one death due to Hodgkin's disease. There were seven fatal second cancers and two non-neoplastic treatment-related deaths, equally distributed between the nodular and diffuse groups. We conclude that nodular lymphocyte predominance Hodgkin's disease may have important clinical as well as immunophenotypic differences from other forms of Hodgkin's disease, and that patients with this condition should be followed carefully because of the possibility of late relapse.

    View details for Web of Science ID A1988L784400004

    View details for PubMedID 3336412

  • T-CELL ANTIGEN DEFICIENCIES AND CLONAL REARRANGEMENTS OF T-CELL RECEPTOR GENES IN PAGETOID RETICULOSIS (WORINGER-KOLOPP DISEASE) NEW ENGLAND JOURNAL OF MEDICINE Wood, G. S., Weiss, L. M., Hu, C. H., Abel, E. A., Hoppe, R. T., Warnke, R. A., Sklar, J. 1988; 318 (3): 164-167

    View details for Web of Science ID A1988L714100007

    View details for PubMedID 3257292

  • DISSECTION OF THE MECHANISMS OF IMMUNE INJURY IN RHEUMATOID-ARTHRITIS, USING TOTAL LYMPHOID IRRADIATION ARTHRITIS AND RHEUMATISM Gaston, J. S., Strober, S., SOLOVERA, J. J., GANDOUR, D., Lane, N., Schurman, D., Hoppe, R. T., CHIN, R. C., Eugui, E. M., Vaughan, J. H., Allison, A. C. 1988; 31 (1): 21-30

    Abstract

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation. After radiotherapy, there was a marked decrease in the number and function of peripheral blood helper/inducer (Leu-3+) T lymphocytes, in the spontaneous secretion of interleukin-1 by synovial biopsy specimens, and in the activity of the joint disease. In contrast, levels of IgM, IgA, and IgG rheumatoid factors and C3 concentrations in blood and synovial fluid samples did not change significantly after therapy with total lymphoid irradiation.

    View details for Web of Science ID A1988M309400004

    View details for PubMedID 3257873

  • The non-Hodgkin's lymphomas: pathology, staging, treatment. Current problems in cancer Hoppe, R. T. 1987; 11 (6): 363-447

    Abstract

    The non-Hodgkin's lymphomas include a broad range of neoplasms derived from the T cells and B cells and their precursors in the lymphoid system. Although they are not among the most common cancers, the lymphomas have engendered a great deal of interest among researchers because of their interesting biology and responsiveness to therapy. The non-Hodgkin's lymphomas include at least ten major subtypes of diseases with different morphologic characteristics and clinical behavior. Based upon survival characteristics, it is convenient to divide the lymphomas into three broad categories, low grade, intermediate grade, and high grade. The low grade lymphomas usually arise in middle age or older individuals (median age, 55 years). They are derived from B cells and often have a follicular architectural pattern. They usually present with advanced stages of disease, often by virtue of bone marrow involvement. Nevertheless, patients are usually asymptomatic and may even have spontaneous regressions of disease. These lymphomas are responsive to a broad range of therapies including irradiation, single agent or multi-agent chemotherapy, or combined modality therapy. They are also affected by treatment with biologicals such as alpha interferon and monoclonal antibodies. Unfortunately, response to any of these therapies is often transient and relapse is common. The intermediate grade lymphomas include the common large cell lymphomas (follicular or diffuse) and diffuse mixed cell lymphoma. The lymphomas, together with the high grade immunoblastic lymphoma, are often grouped together for the development of management strategies. These lymphomas may be derived from B cells or T cells. They occur over a broader age range than the low grade lymphomas and they are much more aggressive in their natural behavior. Effective treatment programs have been developed for both limited and advanced clinical stages of disease. In limited disease, moderately intensive chemotherapy is often combined with involved field irradiation. In advanced stage disease, more aggressive combination chemotherapy programs are usually employed. From 40% to 80% of patients may be cured with these approaches, depending upon the initial extent of disease. Two types of high grade lymphoma-lymphoblastic and small noncleaved cell are particularly aggressive in their behavior. Lymphoblastic lymphoma is a T cell lymphoma that often arises in adolescent males and presents with a large mediastinal mass, marrow, and CNS involvement. It closely resembles acute lymphoblastic leukemia (ALL) and similarly intensive chemotherapy programs as are utilized in ALL may be successful in its management.(ABSTRACT TRUNCATED AT 400 WORDS)

    View details for PubMedID 3125008

  • MYCOSIS-FUNGOIDES - MANAGEMENT WITH TOPICAL NITROGEN-MUSTARD JOURNAL OF CLINICAL ONCOLOGY Hoppe, R. T., Abel, E. A., DENEAU, D. G., Price, N. M. 1987; 5 (11): 1796-1803

    Abstract

    The technique of treatment, response rate, freedom from relapse, survival, and complications of therapy in 123 patients treated with topical nitrogen mustard (HN2) for cutaneous mycosis fungoides (MF) at Stanford University Medical Center are reviewed. Patients were treated with HN2 in an aqueous or ointment base with equal efficacy. Response rates depended on the extent of skin involvement. In limited plaque (T1) disease, complete and overall response rates were 51% and 88%, respectively, while in generalized plaque (T2) disease they were 26% and 69%. No patients with tumorous involvement (T3) achieved complete skin clearance and all 13 of these patients developed progression of disease. Only two of nine patients with erythrodema (T4) achieved a complete response (CR), and both later relapsed. After achieving a CR, 40% of patients with T1 disease and 60% with T2 disease later relapsed; however, subsequent therapies, including repeat courses of topical HN2, often were successful in achieving later skin clearance. Overall, 42% of T1 patients and 31% of T2 patients were without evidence of MF at last follow-up. When death occurred, it was usually unrelated to MF in the T1 group. However, half of the deaths of patients with T2 disease were attributable to MF. Among the 22 patients with T3 or T4 disease, 80% of deaths were attributable to MF. The most common complication observed was a cutaneous hypersensitivity reaction, which occurred much more commonly with the aqueous than the ointment preparation. Fourteen patients (11%) developed subsequent cutaneous malignancies.

    View details for Web of Science ID A1987K859800016

    View details for PubMedID 3681368

  • SOLITARY PLASMACYTOMA OF BONE - TREATMENT, PROGRESSION, AND SURVIVAL JOURNAL OF CLINICAL ONCOLOGY CHAK, L. Y., Cox, R. S., Bostwick, D. G., Hoppe, R. T. 1987; 5 (11): 1811-1815

    Abstract

    Twenty patients with solitary plasmacytoma of bone were treated by radiation therapy. Local control was achieved in 19 and most patients developed systemic myeloma. To evaluate disease progression, 65 patients, including 45 from published series, were analyzed. Younger patients seemed less likely to progress (P = .06), but other clinical characteristics including site of involvement and paraprotein status did not influence progression. After dissemination, patients had a clinical course similar to patients with stage I myeloma, with a median survival of 47 months. Overall, patients with solitary plasmacytoma of bone had an indolent course of disease, with a median survival of 10.7 years and a 5-, 10-, and 20-year survival of 75%, 52%, and 37%, respectively.

    View details for Web of Science ID A1987K859800018

    View details for PubMedID 3681369

  • LUPUS NEPHRITIS AFTER TOTAL LYMPHOID IRRADIATION - PERSISTENT IMPROVEMENT AND REDUCTION OF STEROID-THERAPY ANNALS OF INTERNAL MEDICINE Strober, S., Farinas, M. C., Field, E. H., SOLOVERA, J. J., Kiberd, B. A., Myers, B. D., Hoppe, R. T. 1987; 107 (5): 689-690

    View details for Web of Science ID A1987K850900015

    View details for PubMedID 3662281

  • MINIMAL LONG-TERM CARDIOPULMONARY DYSFUNCTION FOLLOWING TREATMENT FOR HODGKINS-DISEASE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS WATCHIE, J., Coleman, C. N., Raffin, T. A., Cox, R. S., Raubitschek, A. A., Fahey, T., Hoppe, R. T., VANKESSEL, A. 1987; 13 (4): 517-524

    Abstract

    We studied the long term cardiopulmonary function, at rest and during exercise, of 57 patients who were at least 1 year (mean 5 years) post-treatment for Hodgkin's disease. To establish the maximum degree of dysfunction we studied 40 patients who had extensive intrathoracic disease treated with radiotherapy alone (Exten-X; n = 20) or combined modality therapy (Exten-XC; n = 20). Patients without intrathoracic disease given either prophylactic mantle therapy (Proph-X, n = 10) or no chest irradiation (Control: n = 7) were used as controls. An abnormal electrocardiogram, by virtue of a conduction defect, was observed in seven patients, six in the Exten-X or Exten-XC groups. Borderline abnormalities including ST-T changes, prolonged QT interval, or axis deviation occurred in 14 patients distributed evenly throughout the groups. Resting mean pulmonary function test values were normal in all treatment groups. Exercise tolerance, as indicated by peak oxygen consumption (VO2), was significantly lower for the Exten-XC group compared to Proph-X (p less than 0.01). However, the mean value of VO2 for group Exten-XC was only 15% below that predicted. Of the 12 patients with abnormally low VO2 (greater than 20% below their predicted value), 11 were in the Exten-X or Exten-XC group with no difference between the two groups. Patients who received radiotherapy to at least one lung field, using either the thin lung block technique or open field irradiation, had significantly lower exercise tolerance than those treated with full thickness blocks (p less than 0.05). Despite these abnormalities only a single patient complained of marked dyspnea. We conclude that extensive treatment to the mantle field, especially when followed by chemotherapy in patients with extensive intrathoracic Hodgkin's disease, can result in minimal cardiopulmonary dysfunction in approximately one-third of patients.

    View details for Web of Science ID A1987G828800007

    View details for PubMedID 2435687

  • CENTRAL NERVOUS-SYSTEM INVOLVEMENT IN NON-HODGKINS LYMPHOMA - AN ANALYSIS OF 105 CASES CANCER MacKintosh, F. R., Colby, T. V., PODOLSKY, W. J., Burke, J. S., Hoppe, R. T., Rosenfelt, F. P., Rosenberg, S. A., KAPLAN, H. S. 1982; 49 (3): 586-595

    Abstract

    Records of 105 patients with central nervous system (CNS) lymphoma were analyzed in order to better define the incidence, setting, and management of CNS lymphoma and the role for CNS prophylaxis. Survival was best for patient under 30 years of age treated with whole-brain irradiation and intrathecal (IT) chemotherapy whose CNS involvement was an isolated event (median survival time, 1.8 years). Survival was worst for patients over 30 years of age whose CNS invasion occurred at a time of progressive systemic lymphoma (median time ten weeks if treated with whole-brain irradiation with or without IT chemotherapy). The risk of CNS invasion was greatest for those with lymphoblastic lymphoma. Among patients with Stage IIE, III, or IV histiocytic lymphoma, the risk of CNS involvement was greatest for those with progressive or relapsing disease or involvement of the testes, peripheral blood, or epidural space of the spinal cord.

    View details for Web of Science ID A1982MY94600029

    View details for PubMedID 7059915

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