Bio

Academic Appointments


Administrative Appointments


  • President, ASCO (2005 - 2006)
  • President-Elect, ASCO (2004 - 2005)

Honors & Awards


  • Alwin C. Rambar-James B. D. Mark Award for Excellence in Patient Care, Stanford University School of Medicine (2000)

Research & Scholarship

Current Research and Scholarly Interests


The objectives of the clinical research program are:
1. to improve therapeutic outcomes and/or reduce complications of treatment, and
2. to further elucidate the underlying biology of Hodgkin’s disease (HD) and the non-Hodgkin’s lymphomas (NHL).

The research program is highly collaborative and includes ongoing clinical trials with myeloablative therapy in HD and NHL with the Bone Marrow Transplant team, combined modality trials in HD with Radiation Oncology, clinical-pathologic correlative studies with Pathology, and drug development with an emphasis on targeted therapy for B-cell lymphoma (anti-CD20) with industrial collaborators.

Dr. Horning is chairman of the Lymphoma Committee for the Eastern Cooperative Oncology Group, a forum for extending pilot studies to multi-institutional trials. Dr. Horning supervises a sophisticated multi-relational Lymphoma Database which has information on over 15,000 patients, an excellent resource for prospective and retrospective clinical investigations

Clinical Trials


  • Study of SGN-40 in Patients With Relapsed Diffuse Large B-Cell Lymphoma Not Recruiting

    This is a Phase II, open-label, multidose trial of SGN-40 designed to estimate objective response rate and assess toxicity in patients with relapsed DLBCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ranjana Advani, (650) 724 - 8372.

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  • High Dose Chemotherapy and Allogeneic Hematopoietic Cell Transplant for Non-Hodgkin's Lymphoma Not Recruiting

    To evaluate the role of allogeneic hematopoietic cell transplantation in the treatment of NHL.

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

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  • Efficacy and Safety Study of Fostamatinib Disodium Tablets to Treat T-Cell Lymphoma Not Recruiting

    Patients meeting specific inclusion and exclusion criteria will be enrolled in two stages, 19 patients in Stage 1 and 36 patients in Stage 2. Stage 2 will enroll if 4 or more patients exhibit a response at Week 8 or later in the study. All enrolled patients will be treated with Fostamatinib Disodium until disease progression. Efficacy will be assessed by tumor measurements using CT and PET (when indicated) scans and physical exam at baseline, and scans and physical exam of all disease-involved areas every 8 weeks until progression. Safety will be assessed by periodic physical exams, clinical laboratory studies, and adverse events. All patients will have a follow-up visit 30 days following last study drug treatment. Blood samples for PK assessment will be obtained from all patients enrolled in Stage 1 at protocol defined intervals.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Phase II Poor Risk Diffuse Large B-cell Lymphoma (DLBCL) of Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) Followed by Matched Allogeneic Hematopoietic Transplantation as Consolidation to Autologous Hematopoietic Cell Transplantation (AHCT) Not Recruiting

    The purpose of this study is to develop an alternative treatment for patients with relapsed diffuse large B cell lymphoma who are not likely to be cured by the conventional transplantation regimen.

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

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  • Study of YM155 in Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Subjects Not Recruiting

    A study in subjects with a type of B cell lymphoma (DLBCL)to evaluate the response rate, efficacy, safety and tolerability of YM155

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Office Office, (650) 498 - 7061.

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  • A Study of ONTAK and CHOP in Newly Diagnosed, Peripheral T-Cell Lymphoma Not Recruiting

    Study of ONTAK and CHOP (chemotherapy drugs) to find out their ability to make Peripheral T-cell lymphoma disappear (for any period of time) and potentially lengthen life. The study will also compare what kind of side effects these drugs cause and how often they occur. The hypothesis is that patients with newly diagnosed peripheral T-Cell lymphoma, when given ONTAK + CHOP, will tolerate the treatment and will have a 20% improvement in response rate when compared to CHOP alone.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Rituximab and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Non-Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin's lymphoma.

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

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  • 90Y-IBRITUMOMAB Tiuxetan and AHCI With HD Chemotherapy and Autologous Transplantation for Relapsed or Resistant NHL Not Recruiting

    To test a new way to approach hematopoietic stem cell transplantation for Relapsed or Resistant Non-Hodgkin's Lymphoma.

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

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  • Rituximab in Treating Patients With Low Tumor Burden Indolent Non-Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known which rituximab regimen is more effective in treating indolent non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and comparing them to see how well they work in treating patients with low tumor burden indolent stage III non-Hodgkin's lymphoma or stage IV non-Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office, (650) 498 - 7061.

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  • Phase I/II CPG 7909 + Local XRT in Recurrent Low-Grade Lymphomas Not Recruiting

    This is a single institution phase I / II trial to evaluate the safety, feasibility and efficacy of CpG injections (4 intratumoral injections followed by 6 peri-tumoral injections) combined with local irradiation in patients with recurrent low-grade lymphomas. 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 the 24 hours before and the 24 hours after the radiation, and on days 8 and 15. Weekly doses of CpG will be then administered subcutaneously in the region of previous injections for 6 additional doses.

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

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  • Phase I/II of a CpG-Activated Whole Cell Vaccine Followed by Autologous Immunotransplant for MCL Recruiting

    While autologous hematopoietic stem cell transplant (AHCT) has been shown to cure some subtypes of non-Hodgkin's lymphoma (NHL), mantle cell lymphoma (MCL) still has a prognosis marked by relapse. This study will evaluate the safety and efficacy of treating newly diagnosed MCL patients with an autologous, tumor-derived vaccine followed by re-infusion of vaccine-primed T cells combined with standard autologous hematopoietic stem cell transplant (AHCT). CpG-MCL vaccine is derived from each patient's own tumor, treated in vitro with the immunostimulatory CpG-enriched oligodeoxynucleotide - PF-3512676 - and irradiated. The overall treatment schema is that patients receive: induction chemotherapy, priming vaccinations, leukapheresis to harvest vaccine-primed T cells, preparative myeloablative chemotherapy followed by AHCT, re-infusion of vaccine-primed T-cells ('immunotransplant') and repeat vaccinations zero and three months post-AHCT.

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  • Rituximab, Combination Chemotherapy, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Stage I or Stage II Non-Hodgkin's Lymphoma Not Recruiting

    This phase II trial is studying how well giving rituximab together with combination chemotherapy and yttrium Y 90 ibritumomab tiuxetan works in treating patients with stage I or stage II lymphoma. Drugs used in chemotherapy, such as prednisone, cyclophosphamide, doxorubicin, and vincristine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab and yttrium Y 90 ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining a monoclonal antibody with combination chemotherapy and a radiolabeled monoclonal antibody may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office, (650) 498 - 7061.

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  • Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Older Patients With Non-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. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known if combination chemotherapy is more effective with or without rituximab for non-Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without rituximab in treating older patients who have non-Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Daadi, 65072564.

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  • Vaccine Therapy and GM-CSF in Treating Patients With Progressive Non-Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Vaccines made from a person's cancer cells may make the body build an effective immune response to kill cancer cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may stimulate the immune system in different ways and stop cancer cells from growing. PURPOSE: This phase II trial is studying how well giving vaccine therapy together with GM-CSF works in treating patients with progressive B-cell non-Hodgkin's lymphoma.

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

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  • Bevacizumab and Combination Chemotherapy in Treating Patients With Peripheral T-Cell Lymphoma or Natural Killer Cell Neoplasms Not Recruiting

    RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bevacizumab may also stop the growth of cancer cells by blocking blood flow to the cancer. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with several chemotherapy drugs (combination chemotherapy) works in treating patients with peripheral T-cell lymphoma or natural killer cell neoplasms.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Ahern, (650) 725 - 6413.

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  • A Dose and Schedule Finding Trial With AMG 531 for Chemotherapy Induced Thrombocytopenia (CIT) in Adults With Lymphoma Not Recruiting

    The purpose of this study is to identify a well-tolerated, effective dose and schedule of AMG 531 for the treatment of Chemotherapy Induced Thrombocytopenia (CIT) in subjects with lymphoma receiving multi-cycle chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • A Randomized Phase IIb Placebo-Controlled Study of R-ICE Chemotherapy With and Without SGN-40 for Patients With DLBCL Not Recruiting

    This is a randomized trial to estimate the activity of R-ICE plus SGN-40 vs. R-ICE plus placebo in patients with DLBCL. The study will assess safety and tolerability and will measure any additional clinical benefit observed in patients receiving SGN-40.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Cyclosporine in Treating Patients With Recurrent or Refractory Angioimmunoblastic T-Cell Lymphoma Not Recruiting

    RATIONALE: Cyclosporine may help the immune system slow the growth of angioimmunoblastic T-cell lymphoma. PURPOSE: This phase II trial is studying how well cyclosporine works in treating patients with recurrent or refractory angioimmunoblastic T-cell lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office, (650) 498 - 7061.

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  • A Pivotal Open-Label Trial of Brentuximab Vedotin for Hodgkin Lymphoma Not Recruiting

    This is a single-arm, open-label, multicenter, pivotal clinical trial to evaluate the efficacy and safety of brentuximab vedotin (SGN-35) as a single agent in patients with relapsed or refractory Hodgkin lymphoma.

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

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  • Clinical Trial of PXD101 in Patients With T-Cell Lymphomas Not Recruiting

    This is an open-label, non-randomized trial to assess the effectiveness of PXD101 in patients with recurrent or refractory cutaneous or peripheral and other types of T-cell lymphomas. PXD101 is a new, potent histone deacetylase (HDAC) inhibitor. Patients are treated with belinostat(PXD101) 1000 mg/m2 on days 1-5 of a 21 day cycle.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • A Phase 2 Open Label Trial of Brentuximab Vedotin (SGN-35) for Systemic Anaplastic Large Cell Lymphoma Not Recruiting

    This is a single-arm, open-label, multicenter, clinical trial to evaluate the efficacy and safety of brentuximab vedotin (SGN-35) as a single agent in patients with relapsed or refractory ALCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lan Wang, (650) 723 - 5535.

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  • Enrichment & Purging of Stem Cells in Non-Hodgkin's Lymphoma Not Recruiting

    To evaluate the role of purging the hematopoietic cell graft on outcomes for non-Hodgkin's Lymphoma.

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

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  • Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma 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.

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  • A Phase I Dose Escalation Study of SGN-35 Alone and in Combination With Gemcitabine for CD30-Positive Malignancies Not Recruiting

    This study will examine the safety profile of SGN-35 alone and in combination with gemcitabine. The study will test increasing doses of SGN-35 given weekly to small groups of patients.

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

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  • Gemcitabine and Hodgkin's Disease Chemotherapy Followed by Peripheral Blood Stem Cell Rescue for Hodgkin's Disease Not Recruiting

    Phase II Gemcitabine + HD Chemotherapy Followed by PBSC Rescue for HD

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

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Teaching

2013-14 Courses


Publications

Journal Articles


  • Interim positron emission tomography scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study BLOOD Horning, S. J., Juweid, M. E., Schoeder, H., Wiseman, G., McMillan, A., Swinnen, L. J., Advani, R., Gascoyne, R., Quon, A. 2010; 115 (4): 775-777

    Abstract

    Positive interim positron emission tomography (PET) scans are thought to be associated with inferior outcomes in diffuse large B-cell lymphoma. In the E3404 diffuse large B-cell lymphoma study, PET scans at baseline and after 3 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone were centrally reviewed by a single reader. To determine the reproducibility of interim PET interpretation, an expert panel of 3 external nuclear medicine physicians visually scored baseline and interim PET scans independently and were blinded to clinical information. The binary Eastern Cooperative Oncology Group (ECOG) study criteria were based on modifications of the Harmonization Criteria; the London criteria were also applied. Of 38 interim scans, agreement was complete in 68% and 71% by ECOG and London criteria, respectively. The range of PET(+) interim scans was 16% to 34% (P = not significant) by reviewer. Moderate consistency of reviews was observed: kappa statistic = 0.445 using ECOG criteria, and kappa statistic = 0.502 using London criteria. These data, showing only moderate reproducibility among nuclear medicine experts, indicate the need to standardize PET interpretation in research and practice. This trial was registered at www.clinicaltrials.gov as #NCT00274924 [corrected].

    View details for DOI 10.1182/blood-2009-08-234351

    View details for Web of Science ID 000274086600008

    View details for PubMedID 19767508

  • Cancer Research and Privacy: The Problem With Being Joined at the Hip JOURNAL OF CLINICAL ONCOLOGY Horning, S. J. 2009; 27 (24): 3879-3880

    View details for DOI 10.1200/JCO.2009.23.6695

    View details for Web of Science ID 000269064300003

    View details for PubMedID 19620474

  • 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

  • Maintenance Rituximab After Cyclophosphamide, Vincristine, and Prednisone Prolongs Progression-Free Survival in Advanced Indolent Lymphoma: Results of the Randomized Phase III ECOG1496 Study JOURNAL OF CLINICAL ONCOLOGY Hochster, H., Weller, E., Gascoyne, R. D., Habermann, T. M., Gordon, L. I., Ryan, T., Zhang, L., Colocci, N., Frankel, S., Horning, S. J. 2009; 27 (10): 1607-1614

    Abstract

    To determine if maintenance rituximab (MR) after standard chemotherapy improves progression-free survival (PFS) in advanced-stage indolent lymphoma.Patients with stage III-IV indolent lymphoma with responding or stable disease after cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy were stratified by initial tumor burden, residual disease after CVP (minimal or gross), and histology, and randomly assigned to observation (OBS) or MR 375 mg/m(2) once per week for 4 weeks every 6 months for 2 years. PFS was the primary end point.Three hundred eleven (282 with follicular lymphoma) evaluable patients who received CVP were randomly assigned to OBS (n = 158) or MR (n = 153). Best response improved in 22% MR versus 7% OBS patients (P = .00006). Toxicity was minimal in both study arms. Three-year PFS after random assignment was 68% MR versus 33% OBS (hazard ratio [HR] = 0.4; P = 4.4 x 10(-10) [all patients]) and 64% MR v 33% OBS (HR = 0.4; P = 9.2 x 10(-8) [patients with follicular lymphoma]). There was an advantage for MR regardless of Follicular Lymphoma International Prognostic Index score, tumor burden, residual disease, or histology. In multivariate analysis of MR patients, minimal disease after CVP was a favorable prognostic factor. OS at 3 years was 92% MR versus 86% OBS (HR = 0.6; log-rank one-sided P = .05) and, among patients with follicular lymphoma, OS was 91% MR versus 86% (HR = 0.6; log-rank one-sided P = .08). A trend favoring MR was observed among patients with high tumor burden (log-rank one-sided P = .03).The E1496 study provides the first phase III data in untreated indolent lymphoma that MR after chemotherapy significantly prolongs PFS.

    View details for DOI 10.1200/JCO.2008.17.1561

    View details for Web of Science ID 000266194100015

    View details for PubMedID 19255334

  • Follicular lymphoma, survival, and rituximab: Is it time to declare victory? JOURNAL OF CLINICAL ONCOLOGY Horning, S. J. 2008; 26 (28): 4537-4538

    View details for DOI 10.1200/JCO.2008.16.1398

    View details for Web of Science ID 000259648300005

    View details for PubMedID 18662966

  • F-18-FDG-PET/CT evaluation of response to treatment in lymphoma: when is the optimal time for the first re-evaluation scan? HELLENIC JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Wang, Y., Mari, C., Quon, A., Goris, M. L., Horning, S., Gambhir, S. S. 2008; 11 (3): 153-156

    Abstract

    Assessing the response to treatment as soon after treatment initiation is one of the key reasons for imaging lymphoma patients. The optimal time after initiating treatment for assessing response to treatment has yet to be determined. Therefore, we were prompted to review our experience with serial (18)F-FDG PET/CT in patients undergoing treatment for Hodgkin's disease (HD) and non Hodgkin's lymphoma (NHL). This is a retrospective study (Feb 2003 - Oct 2004) of 20 patients, 11 men and 9 women, with age range of 7-75 years with diagnosis of HD (10) and NHL (10), who had PET/CT at our institution prior, during and at the completion of therapy. Restaging PET/CT was done after 2 cycles of chemotherapy in 10 patients (group A) and after 4 cycles of chemotherapy in 10 pts (group B). A total of 60 scans were reviewed. The DeltaSUV from baseline to first PET/CT was on average 67.6% in group A and 75.1% in group B. This had no statistical significance (P value: 0.31). The DeltaSUV from baseline to post-therapy PET/CT was on average 72.9% in group A and 79.8% in group B. This difference also had no statistical significance (P value: 0.24). The correlation coefficient was 0.98 in group A and 0.80 in group B. Results of PET/CT after 2 cycles of chemotherapy did not statistically differ from the results of PET/CT after 4 cycles of chemotherapy. These results need to be confirmed in larger, prospective, randomized trials.

    View details for Web of Science ID 000262093600003

    View details for PubMedID 19081857

  • Long-term results of autologous hematopoietic cell transplantation for peripheral T cell lymphoma: The Stanford experience BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Chen, A. I., McMillan, A., Neprin, R. S., Horning, S. J., Laport, G. G. 2008; 14 (7): 741-747

    Abstract

    The peripheral T cell lymphomas (PTCL) carry a worse prognosis compared to B cell non-Hodgkin lymphoma. There is no uniform standard therapy for PTCL, and autologous hematopoietic cell transplant (AHCT) is often offered as consolidation in first remission or at relapse because of the poor outcomes with conventional therapy. We conducted a retrospective review of patients who underwent AHCT for PTCL from 1989 to 2006. Fifty-three cases were identified consisting of systemic anaplastic large cell (n = 18), PTCL unspecified (n = 17), angioimmunoblastic (n = 9), nasal type extranodal NK/T (n = 7), hepatosplenic (n = 2), and adult T cell leukemia/lymphoma (n = 1). Fifteen patients were transplanted in first complete or partial response (CR1/PR1), 32 in second or beyond CR or PR (CR2/PR2+), and 11 with primary refractory disease (REF). With a median follow-up was 5 years (range: 1.0-11.5), the 5-year progression-free survival (PFS) and overall survival (OS) were 25% and 48%, respectively. Disease status at AHCT had a significant impact on PFS and OS. The 5-year PFS for patients in CR1/PR1, CR2/PR2+, and REF was 51%, 12%, and 0%, respectively, and the corresponding figures for OS were 76%, 40%, and 30%, respectively. The pretransplant factors that impacted survival were disease status and the number of prior regimens. Histology, age, sex, stage, B symptoms, bone marrow involvement, and duration of first response did not significantly affect PFS or OS. Based on these results, AHCT as consolidation therapy in first complete or partial response may offer a durable survival benefit. However, AHCT with conventional salvage chemotherapy has minimal durable benefit in patients with relapsed or refractory PTCL, and thus novel strategies and/or allogeneic HCT should be more aggressively explored in lieu of AHCT for relapsed/ refractory PTCL.

    View details for DOI 10.1016/j.bbmt.2008.04.004

    View details for Web of Science ID 000256971000002

    View details for PubMedID 18541192

  • Follow-up of adult cancer survivors: New paradigms for survivorship care planning HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA Horning, S. J. 2008; 22 (2): 201-?

    Abstract

    The reality of cancer care in the twenty first century is that patients live longer and are more likely to receive care from multiple providers across diverse delivery systems over many years. To meet the challenge of optimal survivor care, a summary of cancer treatment and a formal plan for survivorship must be explained to patients and shared among providers at the end of cancer treatment. These plans must be dynamic documents that change with the circumstances of individual patients, the growth of knowledge, and the guidelines in specific relevant areas. In the new paradigm, open communication across the spectrum of survivor needs and concerns (as contained in a survivorship care plan) will successfully transition cancer patients to healthy survivors. Survivorship planning must become an integral part of every oncologist's education and practice.

    View details for DOI 10.1016/j.hoc.2008.01.005

    View details for Web of Science ID 000255324200003

    View details for PubMedID 18395145

  • Impact of positive positron emission tomography on prediction of freedom from progression after Stanford V chemotherapy in Hodgkin's disease JOURNAL OF CLINICAL ONCOLOGY Advani, R., Maeda, L., Lavori, P., Quon, A., Hoppe, R., Breslin, S., Rosenberg, S. A., Horning, S. J. 2007; 25 (25): 3902-3907

    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 Web of Science ID 000249416000019

    View details for PubMedID 17664458

  • Non-Hodgkin lymphoma of the breast CANCER Ganjoo, K., Advani, R., Mariappan, M. R., McMillan, A., Horning, S. 2007; 110 (1): 25-30

    Abstract

    Primary lymphoma of the breast has been reported to have a high local and central nervous system recurrence (CNS) rate, suggesting the need for consolidation radiotherapy and CNS prophylaxis. A retrospective study was done to evaluate the institutional experience in this patient population.In all, 37 patients with lymphoma involving the breast at initial diagnosis and managed at Stanford University from 1981-2005 were included. Diagnostic tissue biopsies were obtained either from the breast mass or an involved lymph node. Treatment and response data, patterns of recurrence, and outcomes were reviewed.Diffuse large B cell lymphoma (DLBCL) was the most common histologic subtype seen in 18 of 37 (49%) patients. Follicular and marginal zone subtypes were seen in 38%. Most patients presented with an incidental breast mass in stage I(E) or II(E). Four (11%) patients presented with bilateral breast involvement, with only 1 patient presenting with CNS disease. DLBCL patients received doxorubicin-based chemotherapy, with 70% receiving involved field radiotherapy and a single patient receiving intrathecal therapy. No recurrences occurred in the involved breast and a single parenchymal CNS recurrence was recorded. Among the DLBCL patients, the 5-year progression-free survival (PFS) was 61%, with a median follow-up of 3.8 years (range, 5 months to 19 years) and the 5-year overall survival (OS) was estimated at 82%. Patients with indolent lymphoma had an estimated 5-year PFS of 76% and an OS of 92%.DLBCL of the breast was successfully treated with doxorubicin-based chemotherapy alone or with involved field radiotherapy in an estimated 61% of patients at 5 years. A single CNS recurrence was observed in our series of patients, most of whom presented with limited disease.

    View details for DOI 10.1002/cncr.22753

    View details for Web of Science ID 000247384200003

    View details for PubMedID 17541937

  • 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

  • Angioimmunoblastic T cell lymphoma: Treatment experience with cyclosporine LEUKEMIA & LYMPHOMA Advani, R., Horwitz, S., Zelenetz, A., Horning, S. J. 2007; 48 (3): 521-525

    Abstract

    Angioimmunoblastic T cell lymphoma is a distinct entity for which there is no standard therapy. On the basis of the rationale that CsA may represent a novel drug for AITL, a disease with considerable immune dysregulation, and encouraging case reports, the authors have treated 12 patients with this agent. Ten had failed prior steroids and/or chemotherapy and two had no prior therapy. CsA was administered at a dose of 3 - 5 mg/kg PO bid for 6 - 8 weeks and gradually tapered by 50 mg every 1 - 3 weeks. Responding patients received a maintenance dose of 50 - 100 mg, with a gradual taper after a maximal response was achieved as tolerated. Doses were titrated for renal dysfunction or hypertension. CsA levels were not monitored. Eight of 12 patients responded (three complete and five partial remissions). Dose reductions were required in six patients; renal insufficiency (n = 3), fatigue (n = 2), and hypertension (n = 1). Two patients developed acute infections and one patient died shortly after active treatment. These results suggest that CsA deserves further testing as a novel therapy for AITL. By interrupting T-cell activation, CsA may alter the immune dysregulation that characterizes AILT. The efficacy of CsA is being explored in patients with recurrent AILT in a prospective trial (ECOG 2402).

    View details for DOI 10.1080/10428190601137658

    View details for Web of Science ID 000245108100015

    View details for PubMedID 17454592

  • 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

  • High-dose carmustine, etoposide, and cyclophosphamide followed by allogeneic hematopoietic cell transplantation for non-Hodgkin lymphoma BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Law, L. Y., Horning, S. J., Wong, R. M., Johnston, L. J., Laport, G. G., Lowsky, R., Shizuru, J. A., Blume, K. G., Negrin, R. S., Stockerl-Goldstein, K. E. 2006; 12 (7): 703-711

    Abstract

    Allogeneic hematopoietic cell transplantation (HCT) has been shown to be curative in a group of patients with aggressive non-Hodgkin lymphoma (NHL). A previous study has demonstrated equivalent outcomes with a conditioning regimen based on total body irradiation and another not based on total body irradiation with preparative therapy using cyclophosphamide, carmustine, and etoposide (CBV) in autologous HCT. We investigated the safety and efficacy of using CBV in an allogeneic setting. Patients were required to have relapsed or be at high risk for subsequent relapse of NHL. All patients had a fully HLA-matched sibling donor. Patients received carmustine (15 mg/kg), etoposide (60 mg/kg), and cyclophosphamide (100 mg/kg) on days -6, -4, and -2, respectively, followed by allogeneic HCT. All patients were treated with cyclosporine and methylprednisolone as prophylaxis for graft-versus-host disease (GVHD). Thirty-one patients (median age, 46 years) who were felt to be inappropriate candidates for autologous transplantation were enrolled. Each subject had a median of 3 previous chemotherapy regimens. All patients engrafted. Fifteen of 31 patients are alive. Median follow-up time was 11.5 months (range, .4-126). There were 8 deaths due to relapse. Nonrelapse mortality (n = 8) included infection (n = 3), GVHD (n = 2), diffuse alveolar hemorrhage (n = 1), veno-occlusive disease in the setting of concurrent acute GVHD of the liver (n = 1), and leukoencephalopathy (n = 1). Probabilities of event-free survival and overall survival were, respectively, 44% (95% confidence interval, 26%-62%) and 51% (33%-69%) at 1 year and 44% (26%-62%) and 47% (29%-65%) at 5 years. Probability of relapse was 33% (15%-51%) at 1 year and 5 years. Probability of nonrelapse mortality was 31% (13%-49%) at 1 year and 5 years. Incidences were 29% for acute GVHD and 39% for chronic GVHD. None of the 12 patients who developed chronic GVHD has disease recurrence. Patients who had required >3 previous chemotherapy regimens before HCT had an increased probability of relapse. CBV is an effective preparative regimen for patients with aggressive NHL who undergo allogeneic HCT.

    View details for DOI 10.1016/j.bbmt.2006.02.009

    View details for Web of Science ID 000238774800002

    View details for PubMedID 16785059

  • Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma JOURNAL OF CLINICAL ONCOLOGY Habermann, T. M., Weller, E. A., Morrison, V. A., Gascoyne, R. D., Cassileth, P. A., Cohn, J. B., Dakhil, S. R., Woda, B., Fisher, R. I., Peterson, B. A., Horning, S. J. 2006; 24 (19): 3121-3127

    Abstract

    To address early and late treatment failures in older patients with diffuse large B-cell lymphoma (DLBCL), we designed a two-stage randomized trial of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus rituximab plus CHOP (R-CHOP), with a second random assignment to maintenance rituximab (MR) or observation in responding patients.Untreated DLBCL patients who were 60 years or older were randomly assigned to R-CHOP (n = 318) or CHOP (n = 314); 415 responders were randomly assigned to MR (n = 207) or observation (n = 208). The primary end point was failure-free survival (FFS). All P values were two sided.Three-year FFS rate was 53% for R-CHOP patients and 46% for CHOP patients (P = .04) at a median follow-up time of 3.5 years. Two-year FFS rate from second random assignment was 76% for MR compared with 61% for observation (P = .009). No significant differences in survival were seen according to induction or maintenance therapy. FFS was prolonged with MR after CHOP (P = .0004) but not after R-CHOP (P = .81) with 2-year FFS rates from second random assignment of 77%, 79%, 74%, and 45% for R-CHOP, R-CHOP + MR, CHOP + MR, and CHOP, respectively. In a secondary analysis excluding MR patients, R-CHOP alone reduced the risks of treatment failure (P = .003) and death (P = .05) compared with CHOP alone.Rituximab administered as induction or maintenance with CHOP chemotherapy significantly prolonged FFS in older DLBCL patients. After R-CHOP, no benefit was provided by MR. These results, which are consistent with an additive effect of rituximab, suggest that future studies could focus on maintenance strategies with novel agents as well as new induction therapies.

    View details for DOI 10.1200/JCO.2005.05.1003

    View details for Web of Science ID 000238987200025

    View details for PubMedID 16754935

  • Rituximab, Bevacizumab and CHOP (RA-CHOP) in untreated diffuse large B-cell lymphoma: Safety, biomarker and pharmacokinetic analysis LEUKEMIA & LYMPHOMA Ganjoo, K. N., An, C. S., Robertson, M. J., Gordon, L. I., Sen, J. A., Weisenbach, J., Li, S., Weller, E. A., Orazi, A., Horning, S. J. 2006; 47 (6): 998-1005

    Abstract

    Bevacizumab is a humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF-A). Non-Hodgkin's lymphoma patients with high serum VEGF levels have an inferior survival compared to patients with low VEGF levels. Bevacizumab was administered through a central line at 15 mg kg(-1) IV on day 1 followed by rituximab (R) and CHOP on day 2 for cycle 1 and day 1 for cycles 2 - 8. Serum levels of bevacizumab and R were measured at specified time points to assess pharmacokinetics (PK). Plasma and urine samples were also analysed for VEGF. Tumor samples were stained for VEGF, CD31 and factor VIII by immunohistochemistry. Thirteen patients with newly-diagnosed DLBCL received a total of 88 cycles (range 2 - 8, median 7). Best response included five CR, six PR, one SD and one PD with an overall response rate of 85% and complete response rate of 38%. The 12-month PFS is 77% and a median follow-up of 16.9 months for the surviving patients. All tumor samples stained strongly positive for VEGF and there was a marginal association between baseline plasma VEGF and response (p = 0.04). Patients with higher plasma VEGF levels were generally younger and had bulky disease. Micro-vessel density did not correlate with presenting disease characteristics, VEGF expression or response. The PK of bevacizumab and rituximab were not influenced by combined treatment. In this patient population, treatment with RA-CHOP did not result in any episodes of grade 3 or 4 proteinuria, heart failure or hemorrhage. The RA-CHOP combination was generally well tolerated and safe.

    View details for DOI 10.1080/10428190600563821

    View details for Web of Science ID 000239037000007

    View details for PubMedID 16840188

  • Management of advanced stage Hodgkin lymphoma. Journal of the National Comprehensive Cancer Network Advani, R., Ai, W. Z., Horning, S. J. 2006; 4 (3): 241-247

    Abstract

    Although advanced Hodgkin lymphoma is highly curable, balancing the high cure rate with long-term toxicity is challenging. ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) is the standard chemotherapy regimen, producing a high cure rate with acceptable toxicity. Stanford V and BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) are new regimens with encouraging results and are undergoing randomized clinical trials. The International Prognostic Score provides a clinical tool that may help identify patients with high-risk disease who may require a more aggressive regimen. Consolidative radiation's role in managing advanced Hodgkin lymphoma is still controversial, but it is most accepted for bulky or residual disease or after brief chemotherapy. The development and integration of newer imaging tools, such as fluorodeoxyglucose-positron emission tomography imaging, may allow a more precise evaluation of disease and help define which patients might benefit from consolidative treatment.

    View details for PubMedID 16507271

  • Randomized comparison of ABVD chemotherapy with a strategy that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma: National Cancer Institute of Canada Clinical Trials Group and the Eastern Cooperative Oncology Group JOURNAL OF CLINICAL ONCOLOGY Meyer, R. M., Gospodarowicz, M. K., Connors, J. M., Pearcey, R. G., Bezjak, A., Wells, W. A., Burns, B. E., Winter, J. N., Horning, S. J., Dar, A. R., Djurfeldt, M. S., Ding, K., Shepherd, L. E. 2005; 23 (21): 4634-4642

    Abstract

    We report results of a randomized trial comparing ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy alone with treatment that includes radiation therapy in patients with limited-stage Hodgkin's lymphoma.Patients with nonbulky clinical stage I to IIA Hodgkin's lymphoma were stratified into favorable and unfavorable risk cohorts. Patients allocated to radiation-containing therapy received subtotal nodal radiation if favorable risk or combined-modality therapy if unfavorable risk. Patients allocated to ABVD received four to six treatment cycles.We evaluated 399 patients. Median follow-up is 4.2 years. In comparison with ABVD alone, 5-year freedom from disease progression is superior in patients allocated to radiation therapy (P = .006; 93% v 87%); no differences in event-free survival (P = .06; 88% v 86%) or overall survival (P = .4; 94% v 96%) were detected. In a subset analyses comparing patients stratified into the unfavorable cohort, freedom from disease progression was superior in patients allocated to combined-modality treatment (P = .004; 95% v 88%); no difference in overall survival was detected (P = .3; 92% v 95%). Of 15 deaths observed, nine were attributed to causes other than Hodgkin's lymphoma or acute treatment-related toxicity.In patients with limited-stage Hodgkin's lymphoma, no difference in overall survival was detected between patients randomly assigned to receive treatment that includes radiation therapy or ABVD alone. Although 5-year freedom from disease progression was superior in patients receiving radiation therapy, this advantage is offset by deaths due to causes other than progressive Hodgkin's lymphoma or acute treatment-related toxicity.

    View details for DOI 10.1200/JCO.2005.09.085

    View details for Web of Science ID 000230872000013

    View details for PubMedID 15837968

  • Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-Cell lymphoma, progressive after rituximab JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Younes, A., Jain, V., KROLL, S., Lucas, J., Podoloff, D., Goris, M. 2005; 23 (4): 712-719

    Abstract

    To determine overall response (OR) and complete response (CR) rates, response duration, progression-free (PFS) and overall survival and safety with the tositumomab and iodine-131 tositumomab ((131)I tositumomab) therapeutic regimen in patients with indolent, follicular large-cell, or transformed B-cell lymphoma, progressive after rituximab.From July 1998 to November 1999, 40 patients (24 rituximab nonresponders: 11 with response < 6 months, and five with response > or = 6 months) received a therapeutic dose (0.65 to 0.75 Gy per platelet count) of (131)I tositumomab based on total-body dosimetry in this prospective phase II study. The median number of prior treatments was four; 59% of patients were chemotherapy-resistant.Confirmed OR (65%) and CR (38%) rates were not significantly associated with prior rituximab response. With a median follow-up of 3.3 years, the median PFS was 10.4 months, 24.5 months for responders, and not reached for CR patients. Among follicular grade 1 or 2 patients with tumors < or = 7 cm (n = 21), the OR and CR rates were 86% and 57%. Estimated 3-year PFS in this subgroup was 48%, compared with 11% for all others (P = .002). Transient grade 3 to 4 marrow toxicity was seen in 50% of patients. Two patients, one of whom received two subsequent chemotherapy regimens, developed secondary myelodysplasia.(131)I tositumomab is effective in CD20-positive lymphoma progressive after rituximab, with a 65% OR rate and median PFS of 24.5 months for responders. Patients with follicular grade 1 or 2 histology and tumors < or = 7 cm achieved very high OR and CR rates, with 48% PFS at 3 years.

    View details for DOI 10.1200/JCO.2005.07.040

    View details for Web of Science ID 000226738900010

    View details for PubMedID 15613695

  • 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

  • Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern cooperative oncology group study 1484 JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Weller, E., Kim, K. M., Earle, J. D., O'Connell, M. J., Habermann, T. M., Glick, J. H. 2004; 22 (15): 3032-3038

    Abstract

    To compare low-dose (30 Gy) radiotherapy (RT) with observation (OBS) in limited-stage aggressive lymphoma patients achieving complete remission (CR) after chemotherapy, and to measure conversion from partial response (PR) to CR with high-dose (40 Gy) RT.From 1984 to 1992, stage I (with risk factors) and II adults with diffuse aggressive lymphoma in CR after eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomly assigned to 30 Gy involved-field RT or OBS. PR patients received 40 Gy RT.Among 172 CR patients, the 6-year disease-free survival (DFS) was 73% for low-dose RT versus 56% for OBS (two-sided P = .05). Failure-free survival (two-sided P = .06), and time to progression (two-sided P = .06) also favored RT. Intent-to-treat analyses yielded similar results. No survival differences were observed. Three RT versus 15 OBS patients relapsed in initial disease sites. At 6 years, failure-free survival was 63% in PR patients; conversion to CR did not significantly influence clinical outcome.For patients in CR after CHOP, low-dose RT prolonged DFS and provided local control, but no survival benefit was observed. The majority of PR patients were event-free at 6 years despite residual radiographic abnormalities. Future efforts should be directed toward improved imaging and more effective systemic therapies.

    View details for DOI 10.1200/JCO.2004.06.088

    View details for Web of Science ID 000223115000010

    View details for PubMedID 15210738

  • Rituximab in stem cell transplantation for aggressive lymphoma. Current hematology reports Horwitz, S. M., Horning, S. J. 2004; 3 (4): 227-229

    View details for PubMedID 15217551

  • Stage I and II follicular non-Hodgkin's lymphoma: Long-term follow-up of no initial therapy JOURNAL OF CLINICAL ONCOLOGY Advani, R., Rosenberg, S. A., Horning, S. J. 2004; 22 (8): 1454-1459

    Abstract

    To analyze the outcome of no initial therapy in stage I and II follicular small-cleaved (FSC) and follicular mixed (FM) non-Hodgkin's lymphoma (NHL) on overall survival, time to treatment, incidence and course of transformation, and cause of death.This was a retrospective analysis. Criteria for selection were patients with stage I and IIA FSC and FM (grades 1 and 2) NHL with therapy deferred for at least 3 months after diagnosis and a minimum follow-up of 1 year.Forty-three patients were identified (11 stage I, 32 stage II), with a median age of 58 years. Reasons for no initial therapy included: physician choice (n = 20), large abdominal radiation field required (n = 10), advanced age (n = 7), concern for xerostomia (n = 4), or patient refusal (n = 2). At a median follow-up of 86 months, 27 patients (63%) had not been treated. The median time to treatment in the remaining 16 patients was 22 months. Four of 16 patients transformed to a higher-grade lymphoma. Nine patients died-six due to progressive lymphoma. Estimated survivals at 5, 10, and 20 years were 97%, 85%, and 22%, respectively.In selected stage I and II follicular NHL patients, deferred therapy is an acceptable approach, as more than half of our patients remained untreated at a median of 6 or more years, and survival was comparable to that seen in reports with immediate treatment.

    View details for DOI 10.1200/JCO.2004.10.086

    View details for Web of Science ID 000220912200016

    View details for PubMedID 15024027

  • Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma BLOOD Horwitz, S. M., Negrin, R. S., Blume, K. G., Breslin, S., Stuart, M. J., Stockerl-Goldstein, K. E., JOHNSTON, L. J., Wong, R. M., Shizuru, J. A., Horning, S. J. 2004; 103 (3): 777-783

    Abstract

    Based on the favorable safety profile and the independent activity of rituximab in B-cell lymphoma, we evaluated its efficacy and toxicity after high-dose therapy (HDT) and autologous hematopoietic cell transplantation (HCT). Thirty-five patients with diffuse large cell (25 patients), mantle cell (3 patients), transformed (3 patients), or other (4 patients) subtypes of B-cell lymphoma received HDT followed by a purged autologous graft. The rituximab schedule was 4 weekly infusions (375 mg/m(2)) starting at day 42 after HCT and, for patients 5 to 35, a second 4-week course 6 months after HCT. All planned therapy was completed in 29 patients. With 30 months' median follow-up, the 2-year event-free survival (EFS) rate was 83% and the overall survival (OS) rate was 88%. For 21 patients with relapsed or refractory large cell lymphoma, the EFS rate was 81% and the OS rate was 85%. Grades 3 to 4 neutropenia occurred in 19 (54%) patients. A prospective study of immune reconstitution included measurements of lymphocyte subsets, immunoglobulins, and response to vaccination. Serious infections were not observed despite delayed B-cell recovery in all patients and suppressed immunoglobulin G (IgG) levels and low pneumococcus antibody titers in a subset. Rituximab after HDT and HCT is feasible, and these phase 2 data support the current US Intergroup phase 3 trial in recurrent/refractory diffuse large cell lymphoma.

    View details for DOI 10.1182/blood-2003-04-1257

    View details for Web of Science ID 000188393800013

    View details for PubMedID 12907446

  • Future directions in radioimmunotherapy for B-cell lymphoma SEMINARS IN ONCOLOGY Horning, S. J. 2003; 30 (6): 29-34

    Abstract

    Rituximab has become a staple in the management of B-cell non-Hodgkin's lymphoma, but it has limited activity as a single agent, with responses in about half of patients with recurrent follicular and low-grade lymphoma. Radioimmunotherapy (RIT) may surmount inherent or acquired antibody resistance by targeting a radionuclide to tumor cells. This strategy is particularly appealing for B-cell lymphoma because CD20 affords an outstanding target and lymphomas are inherently radiosensitive. The efficacy and safety of RIT have been established in the treatment of relapsed or refractory indolent non-Hodgkin's lymphoma, and yttrium 90 ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, Cambridge, MA) was the first RIT agent to be approved by the US Food and Drug Administration. This supplement to Seminars in Oncology seeks to present hematologists and medical oncologists with the most recent developments in RIT with (90)Y ibritumomab tiuxetan for non-Hodgkin's lymphoma, to clarify the role of the medical oncologist in the administration of the ibritumomab tiuxetan regimen, to indicate how and when RIT with (90)Y ibritumomab tiuxetan may most successfully be integrated into the continuum of treatment for patients with B-cell lymphoma, and to describe ongoing clinical trials with (90)Y ibritumomab tiuxetan in B-cell lymphomas.

    View details for DOI 10.1053/j.seminoncol.2003.10.006

    View details for Web of Science ID 000187880300006

    View details for PubMedID 14710401

  • 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

  • Lymphocyte predominant Hodgkin's disease: More patience than patients CANCER JOURNAL Ekstrand, B. C., Horning, S. J. 2002; 8 (5): 367-368

    View details for Web of Science ID 000178894100004

    View details for PubMedID 12416892

  • Lymphocyte predominant Hodgkin's disease. Current oncology reports Ekstrand, B. C., Horning, S. J. 2002; 4 (5): 424-433

    Abstract

    Lymphocyte predominant Hodgkin's disease (LPHD) is a rare type of B-cell lymphoma with unique pathologic and clinical features that distinguish it from other types of Hodgkin's disease. Patients with LPHD tend to be younger males who present with indolent and asymptomatic lymphadenopathy limited to peripheral lymph nodes. The immunophenotype of the malignant lymphocytic and/or histiocytic cells (CD20+, CD15-, CD30-) forms the basis of the pathologic distinction from the subtypes of classical Hodgkin's disease. Despite an excellent response to aggressive upfront combined-modality treatment, patients with LPHD tend to relapse continuously over decades. The benign nature of these relapses and the incidence of late treatment-related toxicity have raised questions about the need for an aggressive upfront approach. Recent insights into the molecular pathogenesis of LPHD and the development of novel targeted therapies promise to improve future treatment.

    View details for PubMedID 12162918

  • Hodgkin's disease BLOOD REVIEWS Ekstrand, B. C., Horning, S. J. 2002; 16 (2): 111-117

    Abstract

    Significant progress has been made over the past decade in the classification, diagnosis, staging, prognosis, and treatment of Hodgkin's disease (HD). A new classification system has recognized differences in the natural history of certain subtypes. The introduction of positron emission tomography has improved the accuracy of non-invasive staging. New prognostic indices have led to the development of risk-adapted treatment strategies. The serious long-term side effects of extended-field radiotherapy have prompted the increasing use of chemotherapy in conjunction with limited radiotherapy for early-stage patients. Combination chemotherapy remains the treatment of choice for advanced HD, and new dose-intense regimens appear to have improved activity. Patients who relapse now have a more favorable prognosis with the availability of active salvage regimens, autologous stem cell transplantation, and novel biologic agents.

    View details for DOI 10.1054/blre.2002.0190

    View details for Web of Science ID 000176713400004

    View details for PubMedID 12127954

  • 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

  • Durable remission in recurrent T-cell-rich B-cell lymphoma with the anti-CD20 antibody rituximab CLINICAL LYMPHOMA Natkunam, Y., Stanton, T. S., Warnke, R. A., Horning, S. J. 2001; 2 (3): 185-187

    Abstract

    A diagnostic continuum exists between lymphocyte-predominant Hodgkin's disease, T-cell-rich B-cell lymphoma (TCRBCL), and diffuse large B-cell lymphoma. While TCRBCLs are uncommon, their clinical and morphologic presentation can mimic other Hodgkin's and non-Hodgkin's lymphomas from which they must be distinguished for diagnosis and treatment. We present an unusual case of a 30-year-old man with recurrent TCRBCL arising from lymphocyte-predominant Hodgkin's disease with remarkable response to treatment with the anti-CD20 antibody, rituximab.

    View details for Web of Science ID 000173328300009

    View details for PubMedID 11779297

  • 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

  • Efficacy and toxicity of a CCNU-containing high-dose chemotherapy regimen followed by autologous hematopoietic cell transplantation in relapsed or refractory Hodgkin's disease BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Stuart, M. J., Chao, N. S., Horning, S. J., Wong, R. M., Negrin, R. S., JOHNSTON, L. J., Shizuru, J. A., Long, G. D., Blume, K. G., Stockerl-Goldstein, K. E., Goldstein, S. 2001; 7 (10): 552-560

    Abstract

    High-dose CBV (cyclophosphamide, carmustine, and etoposide) in combination with autologous HCT achieves survival rates of approximately 50% at 5 years in recurrent or refractory Hodgkin's disease (HD). However, carmustine (BCNU) dose-dependent pulmonary toxicity occurs in 20% to 30% of patients. A decreased incidence of interstitial pneumonitis as well as a possible benefit in efficacy has been reported with lomustine (CCNU) compared to BCNU in the standard dose setting. In a dose-escalation study, we substituted CCNU for BCNU in the CBV regimen for 16 patients with HD (n = 12) or non-Hodgkin's lymphoma (n = 4). Based on the promising results, an additional 47 consecutive patients with HD were treated with the following regimen: CCNU (15 mg/kg) orally on day -6, etoposide (60 mg/kg) intravenously on day -4, and cyclophosphamide (100 mg/kg) intravenously on day -2. Peripheral blood progenitor cells and/or bone marrow were infused on day 0. With a median follow-up for the surviving patients of 3.2 years (range, 0.8-9.9 years), the 3-year overall survival rate was 57% (CI, +/-15%), event-free survival was 52% (CI, +/-14%), and freedom from progression was 68% (CI, +/-14%). There were 21 deaths, 10 due to HD. Six patients died due to respiratory failure. Interstitial pneumonitis occurred in 63% of patients and could not be correlated with prior chest radiotherapy. This regimen demonstrated survival rates similar to those of historical studies that used the CBV regimen. However, the incidence of interstitial pneumonitis was in excess of expected.

    View details for Web of Science ID 000172275500004

    View details for PubMedID 11760087

  • 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

  • Advances in the treatment of Hodgkin's lymphoma CURRENT OPINION IN HEMATOLOGY Horwitz, S. M., Horning, S. J. 2000; 7 (4): 235-240

    Abstract

    Given the successful treatment for most patients with Hodgkin's lymphoma, efforts have been directed primarily toward improving outcomes for the minority of patients with poor prognosis or relapsed disease or reducing the late effects of therapy for long-term survivors. Recently, a simple and clinically useful prognostic scoring system was developed for patients with advanced disease. This system allows better risk assessment for individual patients and more uniformity among patients participating in clinical trials. In addition, trials using newer chemotherapeutic regimens such as Stanford V or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) are maturing with promising results. Other studies are helping to define the role of high-dose therapy for patients with Hodgkin's lymphoma, although biologic treatments such as cellular or antibody-based therapies are still in early phases of development. Lastly, positron emission tomographic scanning is emerging as a useful tool in staging and following Hodgkin's lymphoma.

    View details for Web of Science ID 000165671600006

    View details for PubMedID 10882179

  • 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

  • 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

  • Autologous hematopoietic cell transplantation in Hodgkin's disease BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION JOHNSTON, L. J., Horning, S. J. 2000; 6 (3A): 289-300

    Abstract

    The use of HDT and AHCT in Hodgkin's disease patients with early relapsed and refractory disease is supported by historical comparisons. In regard to the late relapsed patient or the newly diagnosed high-risk patient, the role AHCT plays would ideally be answered by well-controlled phase 3 trials. A surrogate approach would be the comparison of AHCT data with well-matched historical controls. It is important, however, to be mindful of the changes that have occur red in the therapy of the newly diagnosed and relapsed HD patient (ABVD replacing MOPP regimens) and the impact these changes may or may not have on nonrelapse mortality in the autografted and nonautografted setting. In addition, the incorporation of consistent prognostic factors in any trial design may identify groups of relapsed or refractory and high-risk HD patients who may or may not gain benefit from HDT. The most effective and efficient route to answering these treatment questions is enrollment of patients in well-controlled and well-designed clinical trials.

    View details for Web of Science ID 000090022500001

    View details for PubMedID 10905766

  • High-dose therapy with hematopoietic cell transplantation for patients with central nervous system involvement by non-Hodgkin's lymphoma BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Alvarnas, J. C., Negrin, R. S., Horning, S. J., Hu, W. W., Long, G. D., Schriber, J. R., Stockerl-Goldstein, K., Tierney, K., Wong, R., Blume, K. G., Chao, N. J. 2000; 6 (3A): 352-358

    Abstract

    Central nervous system (CNS) involvement by non-Hodgkin's lymphoma (NHL) carries a poor patient prognosis whether it occurs as a primary site of disease or secondarily in patients with systemic disease. In a group of 481 patients undergoing high-dose therapy with hematopoietic cell transplantation (HCT) for NHL, 15 patients (3.1%) were identified with CNS involvement. Two patients had primary CNS lymphoma, and 13 had secondary disease. All patients received intrathecal chemotherapy, and 13 received CNS radiotherapy before transplantation. Fourteen patients received systemic chemotherapy. At the time of transplantation, both patients with primary CNS lymphoma and 8 patients with secondary disease had achieved a complete response, 3 patients had achieved a partial response, 1 had failed induction therapy, and 1 had progression of CNS disease before high-dose therapy. Fourteen patients received carmustine, etoposide, and cyclophosphamide as the preparative regimen, and 1 patient received fractionated total body irradiation instead of carmustine. The 2 patients with primary CNS lymphoma were alive and free of disease, 1 at 1,085 days after HCT and 1 at 3,704 days after HCT. The actuarial 5-year event-free survival (EFS) was 46% +/- 26%, and overall survival (OS) was 41% +/- 28%. The median EFS and OS were 2.2 and 1.5 years, respectively. Three patients experienced symptomatic memory loss or intellectual decline after therapy, 1 patient developed paraplegia, and 1 patient had a thrombotic stroke 20 months after HCT. Despite treatment-related toxicities, 7 patients responding to quality-of-life questions at approximately 1 year after HCT gave their overall quality of life a median rating of 9 out of a possible 10 (range, 6-10). High-dose therapy with autologous HCT can produce extended EFS in patients with secondary CNS lymphoma and possibly in those with primary CNS NHL.

    View details for Web of Science ID 000090022500008

    View details for PubMedID 10905773

  • Favorable treatment outcome in non-Hodgkin's lymphoma patients with "poor" mobilization of peripheral blood progenitor cells BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Stockerl-Goldstein, K. E., Reddy, S. A., Horning, S. J., Blume, K. G., Chao, N. J., Hu, W. W., JOHNSTON, L. J., Long, G. D., Strober, S., Wong, R. M., Feiner, R. H., Kohler, S., Negrin, R. S. 2000; 6 (5): 506-512

    Abstract

    Our purpose was to evaluate the outcome and costs of high-dose chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation in patients with the inability to mobilize sufficient numbers of PBPCs to allow rapid engraftment after PBPC transplantation. We treated 172 consecutive non-Hodgkin's lymphoma (NHL) patients with cyclophosphamide and granulocyte colony-stimulating factor followed by apheresis to collect PBPCs. The cells were separated on a Percoll gradient and purged with monoclonal antibodies and complement. The patients were categorized as "good" mobilizers if a collection of > or =2 x 10(6) CD34+ cells/kg was obtained (n = 138, 80%) or "poor" mobilizers if <2 x 10(6) CD34+ cells/kg were obtained (n = 34, 20%). With a median follow-up of 3.5 years, there is no statistically significant difference in actuarial event-free survival, overall survival, or relapse for good mobilizers compared with poor mobilizers. However, there was a trend toward increasing nonrelapse, transplantation-related mortality of 11.8% for poor mobilizers versus 3.6% for good mobilizers (P = .08) and early death from all causes including relapse within 120 days (poor 20.6% versus good 8.7%, P = .06). The total cost for bone marrow transplantation-related care was significantly higher, at $140,264 for poor mobilizers versus $80,833 for good mobilizers (P = .0001). The population of patients with NHL who mobilize PBPCs poorly into the circulation have a higher cost for posttransplant support. However, there is no significant difference in relapse, event-free survival, or overall survival for such patients compared with those who mobilize PBPCs easily.

    View details for Web of Science ID 000090049700004

    View details for PubMedID 11063379

  • Autologous hematopoietic cell transplantation in non-Hodgkin's lymphoma HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA Johnston, L. J., Horning, S. J. 1999; 13 (5): 889-?

    Abstract

    High-dose chemotherapy and AHCT is the therapy of choice for patients with chemosensitive relapsed DLCL, but the part it plays in primary therapy in high-risk NHL patients and in primary and salvage therapy for non-DLCL subtypes remains to be clarified. The continuation of phase III trials is the most efficient and effective route to defining this role. A large number of NHL patients succumb to their disease, so it is hoped that alternate therapies, such as cytokines, monoclonal antibodies, and vaccines, may improve the results of HDT.

    View details for Web of Science ID 000083419100002

    View details for PubMedID 10553254

  • Treatment of early-stage Hodgkin's disease SEMINARS IN HEMATOLOGY Advani, R. H., Horning, S. J. 1999; 36 (3): 270-281

    Abstract

    The management of early-stage Hodgkin's disease has been evolving over the past 25 years, largely due to recognition of early and late complications associated with radiation therapy and the demonstration of minimally toxic but effective chemotherapy. Thus, extended-field radiation is no longer the "gold standard" of treatment. Rather, combined modality approaches with abbreviated chemotherapy and limited radiation, which obviates the need for precise staging offered by laparotomy, provide excellent results with the potential for fewer adverse late effects. Several controlled clinical trials are ongoing to determine the minimal duration of chemotherapy and extent and dose of radiotherapy that will not compromise the excellent cure rate of early-stage disease.

    View details for Web of Science ID 000081774400007

    View details for PubMedID 10462327

  • Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas JOURNAL OF CLINICAL ONCOLOGY Cheson, B. D., Horning, S. J., Coiffier, B., Shipp, M. A., Fisher, R. I., Connors, J. M., Lister, T. A., Vose, J., Grillo-Lopez, A., Hagenbeek, A., Cabanillas, F., Klippensten, D., Hiddemann, W., Castellino, R., Harris, N. L., Armitage, J. O., Carter, W., Hoppe, R., Canellos, G. P. 1999; 17 (4): 1244-1253

    Abstract

    Standardized guidelines for response assessment are needed to ensure comparability among clinical trials in non-Hodgkin's lymphomas (NHL). To achieve this, two meetings were convened among United States and international lymphoma experts representing medical hematology/oncology, radiology, radiation oncology, and pathology to review currently used response definitions and to develop a uniform set of criteria for assessing response in clinical trials. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. Single-photon emission computed tomography gallium scans are encouraged as a valuable adjunct to assessment of patients with large-cell NHL, but such scans require appropriate expertise. Flow cytometric, cytogenetic, and molecular studies are not currently included in response definitions. Response rates may be the most important objective in phase II trials where the activity of a new agent is important and may provide support for approval by regulatory agencies. However, the goals of most phase III trials are to identify therapies that will prolong the progression-free survival, if not the overall survival, of the treated patients. We hope that these guidelines will serve to improve communication among investigators and comparability among clinical trials until clinically relevant laboratory and imaging studies are identified and become more widely available.

    View details for Web of Science ID 000079496300021

    View details for PubMedID 10561185

  • Advances in the management of Hodgkin's and non-Hodgkin's lymphoma. Current opinion in hematology Davis, T. A., Horning, S. J. 1998; 5 (4): 259-263

    Abstract

    Recent developments in the management of lymphoma continue to refine our approach to the disease. There is increasing acceptance of the International Lymphoma Study Group classification for non-Hodgkin's lymphoma. Identification of a new viral agent associated with certain subtypes of lymphoma and new immunologic therapies change our perspective on the disease. New data on treatment results further elucidate the role of radiotherapy and high-dose therapy in Hodgkin's disease and the non-Hodgkin's lymphomas.

    View details for PubMedID 9747632

  • A prognostic score for advanced Hodgkin?s disease. New England Journal of Medicine Hasenclever D, Diehl V, Armitage JO, Assouline D, Bjorkholm M, Brusamolino E, Cannelos GP, Carde P, Crowther D, Cunningham D, Eghbali H, Ferme C, Fisher RI, Glick JH, Glimelius B, Gobbi PG, Holte H, Horning SJ et al. 1998; 229 (21): 1506?14
  • Primary refractory Hodgkin's disease. Annals of oncology Horning, S. J. 1998; 9: S97-101

    Abstract

    Primary refractory Hodgkin's disease may generally be defined as progression of disease during induction treatment or a partial or transient response (< 60 days) to induction therapy. Salvage chemotherapy is inadequate in this patient population; fewer than 10% of patients survive for 10 years or longer. Improved outcomes after failure of primary induction therapy have been reported with myeloablative therapy and autografting. The projected event-free survivals ranged from 18%-49% at four years. Highly selected patients may benefit from salvage radiotherapy, but this may be best accomplished in combination with transplantation. A number of strategies might be considered for increasing the cure rate for the small subset of patients with primary refractory Hodgkin's disease. Among these, identification of patients at high risk for induction failure and modifications of primary treatment to address this risk hold the greatest promise for success.

    View details for PubMedID 9926246

  • High-dose therapy and transplantation for low-grade lymphoma HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA Horning, S. J. 1997; 11 (5): 919-?

    Abstract

    Because of the indolent natural history of low-grade lymphomas, long follow-up is needed to assess the overall success of high-dose therapy and autografting. Results to date suggest that patients with brief first or second remission with chemotherapy or those who attain only a partial remission with second-line or subsequent chemotherapy, but remain drug sensitive, may enjoy prolonged remissions relative to conventional treatment. The role of autografting in first remission is uncertain because the data from clinical trials are not mature. Furthermore, the risk of myelodysplasia after transplantation, the broad range of therapeutic alternatives available, and the option to give high-dose therapy upon relapse argue against autografting as primary treatment. Although purging the autograft of residual lymphoma as assessed by molecular methods has been associated with longer remission duration in one major center, the data from published series are remarkably similar, whether the graft was purged or not. Promising anecdotal data suggest that allogeneic transplantation for low-grade lymphoma deserves further study in prospective clinical trials.

    View details for Web of Science ID A1997YB02500007

    View details for PubMedID 9336722

  • Recent advances in the treatment of Hodgkin's disease. Current opinion in hematology Yuen, A. R., Horning, S. J. 1997; 4 (4): 286-290

    Abstract

    Most patients who present with Hodgkin's disease today can be cured of their disease. Current treatments strive to maintain a high level of efficacy while reducing side effects that limit the quality and length of survival. Sophisticated molecular techniques continue to aid our understanding of the etiology and pathogenesis of this disease. However, the heterogeneity and paucity of "malignant" cells in Hodgkin's disease continue to limit our ability to articulate a coherent and encompassing model.

    View details for PubMedID 9260057

  • Treatment of angioimmunoblastic T-cell lymphoma with cyclosporine ANNALS OF ONCOLOGY Advani, R., Warnke, R., Sikic, B. I., Horning, S. 1997; 8 (6): 601-603

    View details for Web of Science ID A1997XN79200022

    View details for PubMedID 9261530

  • 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

  • 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 Web of Science ID A1997WG07300008

    View details for PubMedID 9028311

  • 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

  • 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

  • Purine analogs in marginal-zone lymphomas. Annals of oncology Horning, S. J. 1996; 7: S21-6

    Abstract

    In an area of lymphoma classification still being defined, marginal-zone lymphomas have distinctive immunohistochemical and cytogenetic features that distinguish them from mantle-cell and follicular lymphomas. There are three subtypes: the extranodal mucosa-associated lymphoid tissue (MALT) lymphomas, the nodal monocytoid B-cell (MBCL) lymphomas, and the splenic marginal-zone lymphomas. The MALT lymphomas represent the neoplastic counterpart of the gut-associated lymphoid tissue, which extends from the jejunum to the rectum. They arise in sites usually containing no lymphoid tissue, such as the stomach, thyroid, and salivary gland. Gastric MALT lymphomas, the most common, are associated with Helicobacter pylori. The MBCL lymphomas closely resemble MALT lymphomas and unlike other non-Hodgkin's lymphomas are commonly composite. Therapy for these lymphomas may include radiation therapy or surgery when disease is of limited extent. However, gastrectomy for gastric MALT lymphomas is not in favor because of the efficacy of antibiotic regimens that can eliminate H. pylori infection. Splenectomy may be indicated for splenic lymphomas. Purine analogs are promising therapeutic agents because they are specific for lymphoid cells. Also, they may prove useful in indolent cancers such as these, because of their activity against dividing and resting cells. Purine analogs may be considered as second-line therapy after alkylating agents for these lymphomas.

    View details for PubMedID 9010575

  • Recent advances in Hodgkin's disease. Current opinion in hematology Yuen, A. R., Horning, S. J. 1995; 2 (4): 262-267

    Abstract

    The treatment of Hodgkin's disease has long superseded our understanding of the pathogenesis of the disease. Recent work adds further evidence to the theory that the Epstein-Barr virus and the bcl2 oncogene play an etiologic role in certain histologic subtypes. Most patients who present with Hodgkin's disease today will be cured with radiation therapy, chemotherapy, or a combination of the two. However, any satisfaction with success in treating the disease should be tempered by the increasing recognition of morbid and potentially lethal complications. Secondary malignancies, cardiotoxicity, and other late effects continue to limit the quality and quantity of life after initial and salvage treatment.

    View details for PubMedID 9372006

  • LONG-TERM SURVIVAL AFTER HISTOLOGIC TRANSFORMATION OF LOW-GRADE FOLLICULAR LYMPHOMA JOURNAL OF CLINICAL ONCOLOGY Yuen, A. R., Kamel, O. W., Halpern, J., Horning, S. J. 1995; 13 (7): 1726-1733

    Abstract

    To describe the course of patients following histologic transformation (HT) from low-grade follicular lymphoma to intermediate- or high-grade non-Hodgkin's lymphoma.Patients were identified from data bases in the Division of Oncology and the Department of Surgical Pathology. HT was defined as the conversion of a follicular small cleaved-cell or follicular mixed small cleaved-cell and large-cell lymphoma to a diffuse large-cell, diffuse mixed small cleaved-cell and large-cell or any high-grade lymphoma.We analyzed the clinical course of 74 low-grade lymphoma patients with histologically proven transformation occurring from 1965 to 1988. The median time from diagnosis to HT was 66 months, and the median age at HT was 58 years. The median duration of survival after transformation was 22 months. Anatomic extent of disease at HT (limited v extensive, P = .01), prior chemotherapy (none v any, P = .01), and response to therapy (complete v partial or none, P = .005) at time of HT were identified as significant predictors of survival after HT in backward-selection Cox regression analysis. Thirty patients attained a complete response to therapy at HT. They had a median survival duration of 81 months after HT.A subset of patients with HT from low-grade follicular lymphoma to intermediate- or high-grade lymphoma enjoys relatively long-term survival. Patients with limited disease and no previous exposure to chemotherapy have the most favorable prognosis.

    View details for Web of Science ID A1995RG15700027

    View details for PubMedID 7602362

  • TRANSPLANTATION OF ENRICHED AND PURGED PERIPHERAL-BLOOD PROGENITOR CELLS FROM A SINGLE APHERESIS PRODUCT IN PATIENTS WITH NON-HODGKINS-LYMPHOMA BLOOD Negrin, R. S., KUSNIERZGLAZ, C. R., Still, B. J., Schriber, J. R., Chao, N. J., Long, G. D., Hoyle, C., Hu, W. W., Horning, S. J., Brown, B. W., Blume, K. G., Strober, S. 1995; 85 (11): 3334-3341

    Abstract

    High-dose chemotherapy with or without radiotherapy followed by autologous transplantation of hematopoietic progenitor cells is an effective treatment for patients with high-risk or relapsed non-Hodgkin's lymphoma. Chemotherapy and/or hematopoietic growth factors have been used to mobilize progenitor cells in the peripheral blood for transplantation. However, the mobilized blood cell products have been found to be frequently contaminated with tumor cells, and techniques have not been developed to purge tumor cells from these products. In addition, the minimum number of hematopoietic progenitor cells required for engraftment has not yet been fully elucidated. We treated 21 patients with a single infusion of cyclophosphamide (4 g/m2) followed by daily administration of granulocyte colony-stimulating factor (G-CSF). After recovery of the white blood cell count, a single 3-hour apheresis collection was performed. The apheresis product was then applied to a discontinuous Percoll gradient. The low-density fractions resulting from this separation procedure were enriched for CD34+ progenitor cells (total cell yield, 19.5%; CD34+ cell recovery, 81.2%). These enriched cellular products were treated with a panel of anti-B cell or anti-T cell monoclonal antibodies and complement in an effort to remove residual tumor cells. After treatment of the patient with myeloablative therapies, the enriched and purged cells were reinfused. Hematologic recovery was rapid, with median neutrophil engraftment in 10 days [absolute neutrophil count (ANC), greater than 0.5 x 10(9)/L] and 11 days (ANC, greater than 1.0 x 10(9)/L). Median platelet transfusion independence required 13 days. The rapidity of multilineage engraftment correlated with the number of CD34+ cells per kilogram that were infused. Patients who received more than 2 x 10(6) CD34+ cells per kilogram had rapid hematologic engraftment, whereas those patients transplanted with less than 2 x 10(6) CD34+ cells per kilogram had slower platelet recovery. Modeling studies using a lymphoma cell line with a t(14; 18) chromosomal translocation demonstrated the successful removal of tumor cells assayed using the polymerase chain reaction (PCR) after the processing and purging. Four of the 21 patients had PCR-detectable lymphoma cells in the bone marrow and peripheral blood; however, the enriched and purged blood products reinfused in all four did not contain detectable tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS)

    View details for Web of Science ID A1995RA13600043

    View details for PubMedID 7538824

  • 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

  • A NEW PREPARATORY REGIMEN FOR AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR PATIENTS WITH LYMPHOMA CANCER Chao, N. J., Kastrissios, H., Long, G. D., Negrin, R. S., Horning, S. J., Wong, R. M., Blaschke, T. F., Blume, K. G. 1995; 75 (6): 1354-1359

    Abstract

    This trial studied the feasibility and efficacy of a new preparatory regimen for autologous bone marrow transplantation for patients with advanced lymphoid malignancies.Twenty-one patients with Hodgkin's disease (n = 12) and non-Hodgkin's lymphoma (n = 9) were treated in this study. Lomustine was substituted for carmustine) in a dose-escalation study with an initial dose of 6 mg/kg and increasing by 3 mg/kg in groups of four patients. The preparatory regimen consisted of lomustine (6-15 mg/kg) orally on Day -6, etoposide (60 mg/kg) intravenously (i.v.) on Day -4, and cyclophosphamide (100 mg/kg) i.v. on Day -2. Peripheral blood progenitor cells and/or bone marrow were infused on Day 0.Lomustine was well tolerated in all patients with no significant toxicity specific to this drug. Engraftment was prompt: the time to achieving greater than or equal to 500 granulocytes/microliters was 12 days (range, 9-16 days) and the time to achieving greater than or equal to 25,000 platelets/microliters without transfusion support was 16 days (range, 9-22 days). Five patients experienced interstitial pneumonitis, three of whom had active or recent interstitial pneumonitis before bone marrow transplantation, and one who just completed mantle irradiation. Three patients died from this preparatory regimen, one of progressive interstitial pneumonitis, one of Legionella pneumonia, and one of multiorgan failure. Three patients with non-Hodgkin's lymphoma relapsed. Fourteen patients are currently alive and disease free to date. The actuarial are currently alive and disease free to date. The actuarial disease free survival was 57%, with a median follow-up of 23 months (range, 1-48 months).The preparatory regimen consisting of lomustine/etoposide/cyclophosphamide is active in treating patients with lymphomas. Further trials with high doses of lomustine are warranted.

    View details for Web of Science ID A1995QL72800017

    View details for PubMedID 7882286

  • 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

  • FOLLICULAR LARGE-CELL LYMPHOMA - INTERMEDIATE OR LOW-GRADE JOURNAL OF CLINICAL ONCOLOGY Bartlett, N. L., Rizeq, M., Dorfman, R. F., Halpern, J., Horning, S. J. 1994; 12 (7): 1349-1357

    Abstract

    To evaluate the benefit of anthracycline-based chemotherapy, identify prognostic factors, and determine the value of the International Prognostic Factors Index for patients with follicular large-cell (FLC) lymphoma.This retrospective study includes 96 patients with FLC lymphoma treated at Stanford University Medical Center between 1969 and 1991. Fifty-five patients received doxorubicin plus cyclophosphamide-containing chemotherapy regimens, 21 patients received other chemotherapy regimens, 15 patients received radiotherapy only, and five patients received no initial therapy. Thirty-four patients had stage I or II disease and 62 patients had stage III or IV disease.With a median follow-up duration of 5.2 years (range, 1 to 18), the actuarial 5- and 10-year overall survival rates were 75% and 54%, with actuarial 5- and 10-year freedom from progression (FFP) rates of 53% and 42%, respectively. Patients treated with chemotherapy regimens that contained both doxorubicin and cyclophosphamide had a superior actuarial 10-year FFP rate (55% v 25%, P = .06) and overall survival rate (65% v 42%, P = .04) compared with patients treated with other chemotherapy regimens. Only one patient treated with doxorubicin plus cyclophosphamide relapsed after 3 years. In the multivariate analysis, discordant lymphoma and treatment with chemotherapy regimens not containing both cyclophosphamide and doxorubicin predicted for worse FFP and overall survival rates. In addition, poor performance status and increasing areas of diffuse histology predicted for a worse survival, while anemia and male sex predicted for a worse FFP. The age-specific International Index was useful in predicting outcome; however, few patients with FLC lymphoma had high-risk features.The plateau in FFP implies that patients with FLC lymphoma enjoy sustained remissions after standard anthracycline-based chemotherapy. FLC lymphoma should continue to be approached as an intermediate-grade lymphoma with curative intent.

    View details for Web of Science ID A1994NW07500003

    View details for PubMedID 8021725

  • TREATMENT APPROACHES TO THE LOW-GRADE LYMPHOMAS BLOOD Horning, S. J. 1994; 83 (4): 881-884

    View details for Web of Science ID A1994MW69200002

    View details for PubMedID 8111061

  • 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

  • Low-grade lymphoma 1993: state of the art. Annals of oncology Horning, S. J. 1994; 5: 23-27

    View details for PubMedID 7911319

  • NATURAL-HISTORY OF AND THERAPY FOR THE INDOLENT NON-HODGKINS-LYMPHOMAS SEMINARS IN ONCOLOGY Horning, S. J. 1993; 20 (5): 75-88

    View details for Web of Science ID A1993MF18200006

    View details for PubMedID 8211209

  • THE EFFICACY OF GRANULOCYTE-COLONY-STIMULATING FACTOR FOLLOWING AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR NON-HODGKINS-LYMPHOMA WITH MONOCLONAL-ANTIBODY PURGED BONE-MARROW LEUKEMIA Schriber, J. R., Negrin, R. S., Chao, N. J., Long, G. D., Horning, S. J., Blume, K. G. 1993; 7 (10): 1491-1495

    Abstract

    Cloned colony-stimulating factors have been shown to accelerate myeloid recovery following autologous bone marrow transplantation. Studies with granulocyte-macrophage colony-stimulating factor (GM-CSF) have demonstrated efficacy in accelerating neutrophil recovery in patients rescued from myeloablative therapy. In our previous study, however, the subset of patients who received monoclonal antibody and complement purged bone marrow grafts followed by GM-CSF recovered neutrophil counts at the same rate as placebo-treated patients. We have now performed a phase II trial to assess whether granulocyte colony-stimulating factor (G-CSF) results in accelerated engraftment in this group of patients. Twenty-three consecutive patients with recurrent non-Hodgkin's lymphoma received G-CSF (10.5 +/- 1.2 micrograms/kg per day) following myeloablative therapy consisting of etoposide (60 mg/kg), cyclophosphamide (100 mg/kg), and either carmustine (15 mg/kg) or fractionated total body irradiation (1200 cGy). All patients received bone marrow grafts which had been purged with a panel of monoclonal antibodies directed against either B or T cell determinants plus complement. Peripheral blood mononuclear cells (PBMC) were not administered to any of the patients in this study. Twenty-one patients engrafted at a median absolute neutrophil count (ANC) greater than 500/microliters at day 12 and ANC greater than 1000/microliters at day 14. The time to myeloid engraftment was significantly shortened compared to our previous experience with either GM-CSF or placebo following identical preparatory regimens (p < 0.01). G-CSF is capable of accelerating myeloid engraftment in patients receiving monoclonal antibody purged bone marrow grafts following myeloablative therapy when compared to historical control groups treated with placebo or GM-CSF.

    View details for Web of Science ID A1993MD20600001

    View details for PubMedID 7692189

  • MACOP-B +/- RADIATION-THERAPY FOR DIFFUSE LARGE-CELL LYMPHOMA - ANALYSIS OF THE STANFORD RESULTS ACCORDING TO PROGNOSTIC INDEXES CANCER Bartlett, N. L., Kwak, L. W., Horning, S. J. 1993; 71 (12): 4034-4042

    Abstract

    The efficacy and toxicity of the MA-COP-B regimen were assessed after outstanding results were reported in diffuse large cell lymphoma (DLCL) by the Vancouver group. The results are reported according to several proposed prognostic indices, including the recent International Prognostic Factors (IPF) Project.Forty-seven patients with untreated DLCL received MACOP-B chemotherapy. Thirty patients, most of whom had bulky disease, also received consolidative radiation therapy (RT). Patient characteristics include median age of 42 years, Stage III/IV (57%), bulky or symptomatic Stage II disease (43%), elevated lactic dehydrogenase (81%) and at least one extranodal site (72%).At a median follow-up of 3.3 years, overall survival was 57% and freedom from progression (FFP) was 52%. The 3-year FFP data were related to tumor extent: 74% for limited stage versus 38% for extensive disease. These data correlated well with four prognostic indices reported in the literature. The IPF index accurately identified low-, intermediate-, and high-risk subgroups.Patients with limited or low-risk DLCL have an excellent prognosis with MACOP-B +/- RT. These results do not support the use of consolidative high-dose therapy and bone marrow transplantation in patients with limited disease, even if bulky or accompanied by an elevated lactic dehydrogenase. Compared to historical CHOP data, MACOP-B +/- RT does not appear to improve outcome for those patients with poor prognostic features, most of whom will fail. The IPF index is a simple, accurate method of distinguishing high-risk patients who require new therapeutic initiatives.

    View details for Web of Science ID A1993LH25600037

    View details for PubMedID 7685238

  • EPSTEIN-BARR VIRUS-ASSOCIATED LYMPHOPROLIFERATIVE DISORDER FOLLOWING AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR NON-HODGKINS-LYMPHOMA TRANSPLANTATION Chao, N. J., Berry, G. J., Advani, R., Horning, S. J., Weiss, L. M., Blume, K. G. 1993; 55 (6): 1425-1428

    View details for Web of Science ID A1993LK58900040

    View details for PubMedID 8390736

  • GRANULOCYTE COLONY-STIMULATING FACTOR MOBILIZED PERIPHERAL-BLOOD PROGENITOR CELLS ACCELERATE GRANULOCYTE AND PLATELET RECOVERY AFTER HIGH-DOSE CHEMOTHERAPY BLOOD Chao, N. J., Schriber, J. R., Grimes, K., Long, G. D., Negrin, R. S., RAIMONDI, C. M., Horning, S. J., Brown, S. L., Miller, L., Blume, K. G. 1993; 81 (8): 2031-2035

    Abstract

    Hematopoietic growth factors have been used to accelerate engraftment after bone marrow transplantation and to "mobilize" peripheral blood progenitor cells (PBPC). We report on the data in 85 consecutive patients with Hodgkin's disease who were treated in a single institution using different methods to obtain PB progenitor cells. Use of granulocyte colony-stimulating factor for mobilization resulted in a significantly accelerated time to recovery of granulocytes (10 days v 12 days, P < .01) when compared with "nonmobilized" PBPC recipients. Similarly, use of mobilized PBPC resulted in a significantly accelerated time to platelet engraftment (13 days v 30 days, P < .001) when compared with "nonmobilized" recipients. Moreover, there was a statistically significant difference in total costs in favor of the group receiving "mobilized" PBPC.

    View details for Web of Science ID A1993KY00500008

    View details for PubMedID 7682454

  • 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

  • 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

  • DYNAMIC ASSESSMENT OF QUALITY-OF-LIFE AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION BLOOD Chao, N. J., Tierney, D. K., Bloom, J. R., Long, G. D., Barr, T. A., STALLBAUM, B. A., Wong, R. M., Negrin, R. S., Horning, S. J., Blume, K. G. 1992; 80 (3): 825-830

    Abstract

    To determine the quality of life in adult patients after autologous bone marrow transplantation (BMT), we administered a questionnaire to a cohort of patients seen at a single referral-based center. The sample included adults 18 years and older during the 1 year following an autologous BMT. Both disease-free patients and those who relapsed with 1-year of follow-up data available were included. Of 59 eligible patients, 58 (98%) responded to the questionnaire. Patients completed a telephone questionnaire administered by a nurse specialist in the field of BMT approximately every 90 days. At the time of initial contact on day +90, the mean quality of life was 7.8 (range, 1 to 10) on a scale of 1 to 10, with 10 being the best. By the end of the first year of follow-up, the mean quality of life was 8.9 (range, 3 to 10). Seventy-eight percent of the patients were employed. Twenty-one percent lost weight during the first year, with the majority reporting voluntary weight loss. Fourteen percent reported difficulties with sexual activity. Only 5% reported difficulty with sleeping or with frequent colds. One patient felt that her appearance was worse, and none of the patients reported a poor appetite. Eighty-eight percent of surviving adult patients reported an above-average to excellent quality of life 1 year following autologous BMT. This outcome is encouraging and suggests that this procedure is not associated with long-term morbidity in the surviving adult patient.

    View details for Web of Science ID A1992JF85500033

    View details for PubMedID 1638031

  • GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) AS AN ADJUNCT TO AUTOLOGOUS HEMATOPOIETIC STEM-CELL TRANSPLANTATION FOR LYMPHOMA ANNALS OF INTERNAL MEDICINE Advani, R., Chao, N. J., Horning, S. J., Blume, K. G., Ahn, D. K., Lamborn, K. R., FLEMING, N. C., Bonnem, E. M., Greenberg, P. L. 1992; 116 (3): 183-189

    Abstract

    To determine the hemopoietic effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients having autologous hemopoietic stem cell transplantation for Hodgkin or non-Hodgkin lymphoma.Placebo or GM-CSF was administered after bone marrow or peripheral blood stem cell transplantation or both in a randomized, double-blind phase III trial by daily intravenous infusion (10 micrograms/kg body weight) until absolute neutrophil counts reached greater than or equal to 1000/mm3 on 3 consecutive days.Bone marrow transplantation unit in a university hospital.Sixty-nine consecutive patients with Hodgkin or non-Hodgkin lymphoma received GM-CSF (36 patients) or placebo (33 patients).Patients who received GM-CSF achieved absolute neutrophil counts greater than or equal to 500/mm3 (median, 12 compared with 16 days, P = 0.02) and absolute neutrophil counts greater than or equal to 1000/mm3 (median, 15 compared with 24 days, P less than 0.001) more quickly than patients who received placebo. Multivariate analysis indicated that use of GM-CSF, peripheral blood stem cells, and unpurged bone marrow were the strongest predictors for early neutrophil recovery greater than 500/mm3. Bacterial infections were significantly reduced in the GM-CSF group (P = 0.04). Delayed engraftment (neutrophils less than 500/mm3 at day 30) occurred in 26% and 17% of the placebo and GM-CSF groups, respectively, and correlated with the absence of detectable myeloid progenitor cells (colony-forming units-granulocyte macrophage, CFU-GM) (P less than 0.001) in marrow aspirate specimens obtained on day 15. Time to platelet independence, duration of hospital stay, severe adverse reactions, relapse, and disease-free survival rates did not differ significantly between the two groups.Administration of GM-CSF after autologous hemopoietic stem cell transplantation in patients with lymphoma resulted in accelerated myeloid recovery, particularly in patients who received peripheral blood stem cells and nonpurged bone marrow, and was associated with a decreased incidence of bacterial infections.

    View details for Web of Science ID A1992HB35600002

    View details for PubMedID 1345803

  • CLINICAL-SIGNIFICANCE OF MORPHOLOGICAL SUBDIVISION IN DIFFUSE LARGE CELL LYMPHOMA CANCER Kwak, L. W., Wilson, M., Weiss, L. M., Horning, S. J., Warnke, R. A., Dorfman, R. F. 1991; 68 (9): 1988-1993

    Abstract

    Although diffuse large cell lymphomas can be morphologically divided into large cell (DLC) and immunoblastic (IBL) subtypes, the clinical significance of this subdivision remains controversial. The initial diagnostic materials from 85 patients with recorded diagnoses of diffuse large cell lymphoma who were treated at Stanford between 1975 and 1986 with cyclophosphamide, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP); methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M-BACOD); or methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were retrospectively reviewed by a panel of hematopathologists and classified according to morphologic criteria of the Working Formulation. Based on the criterion of agreement of two of three observers, 60 patients were classified as having DLC, 19 as having IBL, and the lymphomas in 6 patients could not be additionally classified. No significant differences in complete response (CR) rate, freedom from disease progression (FFP), or overall survival were found between the DLC and IBL groups. There was also no significant difference in prognosis between DLC cases additionally subclassified as large cleaved cell (16 patients) and those with large non-cleaved cell (36 patients). Although IBL is considered to be a high-grade lymphoma, the authors concluded that it does not differ significantly in prognosis from DLC lymphoma and, therefore, does not justify a modified treatment selection based on IBL morphologic type alone. Definitive evaluation of the prognostic significance of morphologic subdivision may require a larger cohort of uniformly treated patients.

    View details for Web of Science ID A1991GK16800022

    View details for PubMedID 1913547

  • MOLECULAR BIOLOGIC STUDIES IN THE CLINICAL-EVALUATION OF NON-HODGKINS-LYMPHOMA HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA Hardy, R., Horning, S. J. 1991; 5 (5): 891-900

    Abstract

    Recent advances in DNA technology have revealed new information about the biology of the non-Hodgkin's lymphomas that is both provocative and exciting. Because these technologies are just beginning to be applied to the clinical evaluation of the non-Hodgkin's lymphomas, the results of clinical studies must be regarded as preliminary. At this time we can only speculate on how they might lead to improved clinical management or provide the basis for new therapies.

    View details for Web of Science ID A1991GF40200005

    View details for PubMedID 1938760

  • SIMILAR OUTCOME OF TREATMENT OF B-CELL AND T-CELL DIFFUSE LARGE-CELL LYMPHOMAS - THE STANFORD EXPERIENCE JOURNAL OF CLINICAL ONCOLOGY Kwak, L. W., Wilson, M., Weiss, L. M., DOGGETT, R., Dorfman, R. F., Warnke, R. A., Horning, S. J. 1991; 9 (8): 1426-1431

    Abstract

    Although previous studies have suggested a relatively poor prognosis for some patients with peripheral T-cell lymphoma, the clinical significance of immunologic phenotype in diffuse large-cell lymphoma (DLCL) remains controversial. One hundred one patients with a uniform morphologic diagnosis of DLCL treated at Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were studied with regard to immunologic phenotype. Immunologic analysis, performed on frozen or paraffin-embedded tissue, identified 77 cases of B-cell origin, 21 cases of T-cell origin, and three cases that lacked B-cell or T-cell markers. Analysis of complete remission (CR) rates (84% v 95%), 5-year actuarial freedom from disease progression (38% v 53%), and 5-year actuarial overall survival (52% v 79%) showed no statistically significant differences in prognosis between B- and T-cell patients, respectively. The 5-year actuarial survival of patients with stage IV T-cell DLCL (56%) also did not differ in a statistically significant way from stage IV B-cell patients (36%). We conclude that treatment selection for DLCL should not be based on immunologic phenotype alone.

    View details for Web of Science ID A1991FY95900016

    View details for PubMedID 1712837

  • CORTICOSTEROID-THERAPY FOR DIFFUSE ALVEOLAR HEMORRHAGE IN AUTOLOGOUS BONE-MARROW TRANSPLANT RECIPIENTS ANNALS OF INTERNAL MEDICINE Chao, N. J., Duncan, S. R., Long, G. D., Horning, S. J., Blume, K. G. 1991; 114 (2): 145-146

    View details for Web of Science ID A1991ER53400010

    View details for PubMedID 1984392

  • 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

  • CEPP(B) - AN EFFECTIVE AND WELL-TOLERATED REGIMEN IN POOR-RISK, AGGRESSIVE NON-HODGKINS-LYMPHOMA BLOOD Chao, N. J., Rosenberg, S. A., Horning, S. J. 1990; 76 (7): 1293-1298

    Abstract

    Eighty-three patients with intermediate- or high-grade non-Hodgkin's lymphoma were treated with CEPP(B) (cyclophosphamide, etoposide [VP-16], procarbazine, and prednisone with or without bleomycin) chemotherapy at Stanford University Medical Center (Stanford, CA) from January 1982 through June 1989. Sixty-nine received CEPP(B) as second-line or subsequent therapy after relapse from previous combination chemotherapy, and 14 patients received CEPP(B) as first-line therapy. Of 75 patients evaluable for response, 30 patients (40%) achieved a complete response (CR) and 24 patients (32%) achieved a partial response (PR), providing an overall response rate of 72%. Complete responses were recorded on 21 of 61 (34%) patients with recurrent disease and 9 of the 14 patients who received CEPP(B) as first line therapy (64%). Myelosuppression was the major side effect of treatment, resulting in eight neutropenic-febrile episodes from a total of 253 courses. A single fatal toxic event occurred on a patient who developed adult respiratory distress syndrome. Overall, CEPP(B) was well-tolerated and proved to be effective palliative therapy for patients with non-Hodgkin's lymphoma after relapse. As such, CEPP(B) may be considered for cytoreduction before ablative therapy and bone marrow transplantation. CEPP(B) may also be considered for initial therapy in selected patients who cannot tolerate doxorubicin-containing regimens.

    View details for Web of Science ID A1990EB07800005

    View details for PubMedID 2207307

  • PROGNOSTIC-SIGNIFICANCE OF ACTUAL DOSE INTENSITY IN DIFFUSE LARGE-CELL LYMPHOMA - RESULTS OF A TREE-STRUCTURED SURVIVAL ANALYSIS JOURNAL OF CLINICAL ONCOLOGY Kwak, L. W., Halpern, J., Olshen, R. A., Horning, S. J. 1990; 8 (6): 963-977

    Abstract

    While diffuse large-cell lymphoma (DLCL) is considered to be highly curable with current therapy, treatment failures are observed even with intensive combination chemotherapy regimens. In order to study the prognostic significance of actual dose intensity of chemotherapy in DLCL, we retrospectively analyzed 115 previously untreated patients treated as Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclosphosphamide, vincristine, prednisone, and bleomycin (MACOP-B). The actual relative dose intensity (RDI), the amount of drug actually administered to each patient during the first 12 weeks of therapy, was calculated as standardized to CHOP and analyzed in addition to clinical factors prognostic for survival by univariate analysis. Multivariate recursive partitioning (tree-structured) survival analysis identified the actual RDI of Adriamycin greater than 75% as the single most important predictor of survival. A model incorporating the actual RDI of Adriamycin and performance status, in combination with serum lactate dehydrogenase (LDH) and extranodal disease, defined three overall prognostic groups of patients with respective 3-year survival rates of 89%, 63%, and 18%. The three prognostic groups remained distinct, even when restricted to complete responders. This model was also predictive of survival when dose intensity was analyzed relative to the optimum dose defined for each of the three regimens and when applied to a subgroup of patients aged 50 years or younger. We conclude that actual RDI is an important prognostic factor for survival in DLCL and that analysis of RDI early in the course of treatment may allow modification of the treatment plan.

    View details for Web of Science ID A1990DG84100004

    View details for PubMedID 2348230

  • DETECTION OF NON-HODGKINS-LYMPHOMA IN THE PERIPHERAL-BLOOD BY ANALYSIS OF ANTIGEN RECEPTOR GENE REARRANGEMENTS - RESULTS OF A PROSPECTIVE-STUDY BLOOD Horning, S. J., Galili, N., Cleary, M., Sklar, J. 1990; 75 (5): 1139-1145

    Abstract

    Analysis of immunoglobulin (Ig) and T-cell receptor gene rearrangements, using Southern blot hybridization, has been applied to peripheral blood lymphocytes (PBL) in 335 samples from patients with non-Hodgkin's lymphoma. The incidence of circulating lymphoma cells detected by gene rearrangement analyses is related to the histologic subtype, clinical stage of disease, and clinical status. Among 104 patients studied at diagnosis, the incidence of positive analyses was 34% in low-grade lymphoma and only 8% in intermediate-grade lymphoma. Clonal Ig gene rearrangements were detected nearly universally in the small lymphocytic histologic subtype. PBL studies were related to the initial stage of disease: positive studies were seen in 35% of patients with stage IV disease, 29% of patients with stage III disease, and 12% of patients with stages I-II disease. The incidence of PBL rearrangements at the time of disease recurrence in 32 patients requiring cytoreductive therapy was 48%, somewhat greater than at initial diagnosis. A group of patients with low-grade lymphoma, who had treatment deferred after diagnosis or recurrence, was also studied; the incidence of PBL rearrangements was 38% in this population. Among 157 patients clinically free of disease, DNA analyses of the PBL were positive in only 10%. Subsequent relapse of disease in 26 patients was antedated by PBL rearrangement in only one patient. Clonal rearrangements detected in 15 patients have been followed by recurrence of clinical disease in only one patient over a median of 24 months from the time of analysis. The lack of detectable rearrangements in the peripheral blood in the majority of patients may be due to methodology or the biology of the disease. These issues may be further addressed with alternative methods for assessment of minimal disease. However, rigorous testing of any new molecular tool requires an adequate patient population in which disease status is closely monitored over a sufficient period of time.

    View details for Web of Science ID A1990CQ87700016

    View details for PubMedID 2306519

  • 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

  • LYMPHOMAS PRESENTING AS HISTOLOGICALLY UNCLASSIFIED NEOPLASMS - CHARACTERISTICS AND RESPONSE TO TREATMENT JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., CARRIER, E. K., Rouse, R. V., Warnke, R. A., Michie, S. A. 1989; 7 (9): 1281-1287

    Abstract

    Malignant lymphoma is frequently diagnosed when immunohistochemical techniques are applied to otherwise unclassified neoplasms. In this analysis of 35 patients with a histologically unclassified neoplasm that expressed leukocyte-common antigen(s) (LCA), actuarial survival was 63%, and 45% of patients were free from disease progression at 30 months following treatment as for lymphoma. The clinical features at diagnosis and the results of combination chemotherapy were found to be similar to a group of patients with a diagnosis of diffuse large-cell lymphoma (DLCL) concurrently treated at this institution. This study further emphasizes the importance of improved diagnostic techniques in the management of histologically unclassified tumors.

    View details for Web of Science ID A1989AM61500015

    View details for PubMedID 2671285

  • NUMBERS OF HOST HELPER T-CELLS AND PROLIFERATING CELLS PREDICT SURVIVAL IN DIFFUSE SMALL-CELL LYMPHOMAS JOURNAL OF CLINICAL ONCOLOGY Medeiros, L. J., Picker, L. J., Gelb, A. B., Strickler, J. G., BRAIN, S. W., Weiss, L. M., Horning, S. J., Warnke, R. A. 1989; 7 (8): 1009-1017

    Abstract

    Diffuse small-cell lymphomas of B-lineage comprise a group of immunophenotypically related lymphoid malignancies that display variable clinical aggressiveness. We compared a variety of clinical, pathologic, and immunologic characteristics of 64 B-lineage diffuse small-cell lymphomas to patient survival in an effort to define prognostically relevant subtypes of these neoplasms. Neither clinical parameters nor histological subclassification correlated with patient outcome. In contrast, three immunologic features of these lymphomas showed a statistically significant relationship with actuarial survival. Neoplasms that manifested greater than or equal to 25% Ki-67+ cells (proliferation-associated antigen), less than 25% Leu 4+ cells (pan-T antigen), or less than 15% Leu 3+ cells (helper/inducer T-subset antigen) were associated with significantly decreased patient survival as compared to neoplasms with the reverse phenotype (P = .02, P = .003, P = .0005, respectively). Leu 3 findings were of particular importance in initial biopsies (P = .0007), while the Ki-67 findings were significant regardless of time of biopsy (P = .01 for biopsies at diagnosis and P = .004 for other biopsies). These data indicate that immunologic analysis can demonstrate subsets of diffuse small-cell lymphoma with different biologic potential, and suggest that such analysis be included in the routine work-up of patients with this type of neoplasm.

    View details for Web of Science ID A1989AG85900006

    View details for PubMedID 2526862

  • 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

  • TREATMENT OF B-CELL LYMPHOMAS WITH ANTI-IDIOTYPE ANTIBODIES ALONE AND IN COMBINATION WITH ALPHA INTERFERON BLOOD Brown, S. L., MILLER, R. A., Horning, S. J., Czerwinski, D., Hart, S. M., MCELDERRY, R., BASHAM, T., Warnke, R. A., Merigan, T. C., Levy, R. 1989; 73 (3): 651-661

    Abstract

    Idiotypes are distinct clonal markers for B-cell lymphomas. Previously we reported the use of anti-idiotype antibodies in the therapy of patients with B-cell malignancies. Because synergy was demonstrated with the addition of alpha interferon to anti-idiotype antibodies in a murine lymphoma model, we performed a clinical trial combining these two agents. Here we provide an update of the original trial of anti-idiotype antibodies alone and report the outcome of the new combination trial. In 16 treatment courses of anti-idiotype antibodies alone there were seven partial responses and one complete response. In 12 courses of combination anti-idiotype antibody and alpha interferon there were two complete responses and seven partial responses. Substantial tumor regressions occurred with minimal toxicity in both trials even in patients refractory to conventional chemotherapy. Tumor specimens obtained at the time of disease progression often contained a preponderance of idiotype-negative lymphoma cells, suggesting that anti-idiotype antibody treatment exerted a strong antitumor effect against antigen-positive cells. Anti-idiotype antibodies have reproducible objective antitumor activity in B-cell lymphoma. The addition of alpha interferon may improve the initial rate of response to this treatment. Strategies that deal effectively with idiotype-negative lymphoma cells should improve the extent and duration of these responses.

    View details for Web of Science ID A1989T250100006

    View details for PubMedID 2465039

  • EXPRESSION OF LFA-1 IN NON-HODGKINS LYMPHOMA CANCER Medeiros, L. J., Weiss, L. M., Picker, L. J., CLAYBERGER, C., Horning, S. J., KRENSKY, A. M., Warnke, R. A. 1989; 63 (2): 255-259

    Abstract

    Lymphocyte function-associated antigen 1 (LFA-1) is a glycoprotein involved in virtually all aspects of the immune response requiring direct cell to cell contact. It has been suggested that lack of LFA-1 expression in lymphomas may represent a mechanism of escape from immunologic surveillance. We investigated the expression of LFA-1 in a series of more than 250 lymphoid neoplasms and reactive lymphoid proliferations using a frozen section immunoperoxidase technique. LFA-1 was expressed by all lymphoid populations in the reactive cases. In contrast, absence of LFA-1 alpha or beta chains was found in 44% of non-Hodgkin's lymphomas, including 50% of B-cell lymphomas. These findings suggest that loss of LFA-1 expression may be of great use in the differential diagnosis of benign versus malignant lymphoproliferations. Eighty percent of initial biopsy specimens of low-grade lymphoma exhibited LFA-1 expression, whereas only 8% of recurrent specimens retained expression of both LFA-1 subunits. However, we found no correlation between LFA-1 expression and clinical course in a series of 64 patients with diffuse large cell lymphomas.

    View details for Web of Science ID A1989R775500008

    View details for PubMedID 2642732

  • 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

  • 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

  • COMPARISON OF HOST-CELL INFILTRATES IN PATIENTS WITH FOLLICULAR LYMPHOMA WITH AND WITHOUT SPONTANEOUS REGRESSION AMERICAN JOURNAL OF CLINICAL PATHOLOGY Strickler, J. G., COPENHAVER, C. M., ROJAS, V. A., Horning, S. J., Warnke, R. A. 1988; 90 (3): 257-261

    Abstract

    The "host cell infiltrates" in five patients with low-grade follicular lymphoma who had spontaneous regression without therapy were studied with the use of immunohistochemical methods applied to frozen sections. These infiltrates were compared with the "host cell infiltrates" in six patients with follicular lymphoma with progressive disease. The group with progressive disease was selected to be similar to the group with spontaneous regression in age, sex, histologic characteristics, and stage of disease. The patients with spontaneous regression had significantly more T-helper cells in the host cell infiltrate than the control patients. There were no statistically significant differences between the two groups in numbers of cytotoxic/suppressor T-cells, macrophages, Tac-positive cells, Leu-7-positive cells, or proliferating cells.

    View details for Web of Science ID A1988P904100005

    View details for PubMedID 2970792

  • 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

  • TRANSFERRIN RECEPTOR EXPRESSION BY NON-HODGKINS LYMPHOMAS - CORRELATION WITH MORPHOLOGIC GRADE AND SURVIVAL CANCER Medeiros, L. J., Picker, L. J., Horning, S. J., Warnke, R. A. 1988; 61 (9): 1844-1851

    Abstract

    The monoclonal antibody OKT9 was applied to cryostat sections of 267 non-Hodgkin's lymphomas and related neoplasms. It was found that the transferrin receptor is expressed by a wide variety of B- and T-lineage non-Hodgkin's lymphomas. The OKT9 staining also was loosely correlated with the three morphologic grades of non-Hodgkin's lymphomas identified by the International Working Formulation. In general, higher grade lymphomas more often and more intensely expressed the T9 antigen. However, transferrin receptor expression by certain histologic subtypes of lymphoma did not correlate with their morphologic grade: low-grade follicular lymphomas expressed the T9 antigen more frequently than diffuse low-grade lymphomas; diffuse small cleaved cell lymphomas were stained by OKT9 less often than other histologic subtypes of intermediate-grade lymphomas; and diffuse immunoblastic lymphomas expressed transferrin receptors less often than the other high-grade histologic subtypes of non-Hodgkin's lymphoma. Intermediate lymphocytic lymphomas, not recognized in the International Working Formulation, were infrequently and weakly stained by OKT9 in a manner similar to diffuse low-grade lymphomas. We obtained clinical follow-up data on 43 individuals with chronic lymphocytic leukemia/small lymphocytic lymphoma and 64 individuals with diffuse large cell and immunoblastic lymphoma. Transferrin receptor expression in these two groups did not correlate significantly with survival.

    View details for Web of Science ID A1988M992800020

    View details for PubMedID 3355978

Conference Proceedings


  • Follicular lymphoma: Have we made any progress? Horning, S. J. OXFORD UNIV PRESS. 2000: 23-27

    Abstract

    Follicular lymphomas are characterized by relatively long median survivals and a continuous pattern of relapse. The heterogeneity in these diseases is increasingly appreciated, leading to concerted efforts to define prognostic factors and risk-adapted strategies. The status of multiple options for treatment including interferon, fludarabine, dose intensification with autologous transplantation, therapy targeting the CD20 antigen and novel approaches is reviewed. The long natural history of follicular lymphoma requires mature data for accurate analysis. However, the achievement of molecular remission as a surrogate endpoint is under active investigation. This is an exciting era for the clinical investigation of follicular lymphoma given the large number of candidate therapies and their potential combinations and permutations. Although the goal of primary treatment remains durable remission and cure, the sequential application of effective, non-cross-resistant treatments may also result in a prolongation of median survival time. It is essential that physicians treating patients with follicular lymphoma demonstrate restraint in the application of new treatments and cooperate in the study of new therapies in carefully designed phase II and phase III trials.

    View details for Web of Science ID 000085882800005

    View details for PubMedID 10707774

  • Brief chemotherapy (Stanford V) and adjuvant radiotherapy for bulky or advanced Hodgkin's disease: An update 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

  • THE STANFORD HODGKINS-DISEASE (HD) STUDIES - AN UPDATE Horning, S. J. STOCKTON PRESS. 1991: 53-55

    Abstract

    Successive, prospective clinical trials for adults with HD have been conducted from 1962-1991. With approximately 75% of patients in continuous remission as a result of current therapy, attention may be focused on reducing treatment complications for the majority of patients and improving efficacy in selected, high risk populations. This overview will describe recently completed and ongoing clinical trials at Stanford University which address these therapeutic objectives.

    View details for Web of Science ID A1991GH79800013

    View details for PubMedID 1890867

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