Bio

Bio


Dr. Laura Johnston currently serves as the Clinical Director and Clinic Chief of the Blood & Marrow Transplantation Division and specializes in Graft Versus Host Disease (GVHD), exploring prevention and treatment of acute and chronic GVHD via clinical trials. She conducts and develops clinical research trials in allogeneic and autologous hematopoietic cell transplantation (HCT) for hematologic malignancies: acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), myeloproliferative disease, non-Hodgkin lymphoma (NHL), Hodgkin disease, myelodysplasia and aplastic anemia.

Clinical Focus


  • Cancer > Blood and Marrow Transplant
  • Cancer > Hematology
  • Blood and Marrow Transplantation
  • Graft-Versus-Host Disease
  • Hematology

Academic Appointments


Administrative Appointments


  • Clinical Director, Division of Blood and Marrow Transplantation Stanford University Medical Center (2009 - Present)
  • BMT Cancer Care Program Physical Lead, Stanford Cancer Institute (2010 - Present)
  • Clinic Chief, Division of Blood and Marrow Transplantation Stanford University Medical Center (2001 - Present)

Boards, Advisory Committees, Professional Organizations


  • Member, BMT Inpatient Utilization Task Force (2012 - Present)
  • Chairperson, BMT Review Committee (2011 - Present)
  • Member, Department of Medicine Quality Council (2011 - Present)
  • Member, Clinically Active Physician Council (2010 - Present)
  • Member, Kaiser/SHC BMT Strategic Alliance for Adult Blood and Marrow/Peripheral Stem Cell Transplantation Work Group (2010 - Present)
  • Preceptor, Ambulatory Medicine Clerkship Med 313 students (2009 - Present)
  • Mentor, Stanford Immersion in Medicine Program (2008 - Present)
  • Member, American Society of Blood and Marrow Transplantation (1996 - Present)
  • Member, American Society of Clinical Oncology (1992 - Present)
  • Member, American Society of Hematology (1992 - Present)

Professional Education


  • Medical Education: University of Minnesota School of Medicine Registrar (1989) MN
  • Board Certification: Hematology, American Board of Internal Medicine (1997)
  • Fellowship: UCSF Medical Center (1995) CA
  • Residency: UCSF Medical Center (1992) CA
  • Internship: UCSF Medical Center (1990) CA
  • BS, University of MN, Microbiology (1982)
  • MD, University of MN, Medicine (1989)

Research & Scholarship

Current Research and Scholarly Interests


I conduct and develop clinical research trials in allogeneic and autologous hematopoietic cell transplantation (HCT) for hematologic malignancies: acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), myeloproliferative disease, non-Hodgkin lymphoma (NHL), Hodgkin disease, myelodysplasia and aplastic anemia.


A specific interest is graft versus host disease (GVHD), exploring prevention and treatment of acute and chronic GVHD via clinical trials. The objectives of the GVHD trials are to reduce the incidence of GVHD, successfully treat acute and chronic GVHD, identify modalities or agents with more tolerable toxicity profiles and ultimately improve morbidity and mortality of affected patients. To this end, I have established a chronic GVHD clinic within the Stanford BMT division which aids in prospectively identifiing appropriate patients for clinical trials. The chronic GVHD clinic allows comprehensive evaluation and treatment for allogeneic BMT patients with new or progressive CGVHD. Through a multidisciplinary approach with my interested colleagues, I hope to impact the formidable effects GVHD has on the quality of life of the post-allogeneic transplant patient.


Other interests include unrelated donor HCT exploring alternate preparative regimens or graft sources as well as HLA typing.

Clinical Trials


  • Bone Marrow Grafting for Leukemia and Lymphoma Recruiting

    The purpose of this study is to obtain tissue samples for ongoing studies regarding transplant outcomes and complications.

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  • Phase 1-2 MAHCT w/ TCell Depleted Graft w/ Simultaneous Infusion Conventional and Regulatory T Cell Recruiting

    For patients with hematologic malignancies undergoing allogeneic myeloablative (MA) HCT with a T cell depleted graft, the infusion of naturally occurring regulatory T cells with conventional T cells (T cell add back) in pre-defined doses and ratios will reduce the incidence of acute graft vs host disease while augmenting the graft vs leukemia effect and improving immune reconstitution.

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  • Protocol For A Research Database For Hematopoietic Stem Cell Transplantation, Other Cellular Therapies and Marrow Toxic Injuries Recruiting

    The primary purpose of the Research Database is to have a comprehensive source of observational data that can be used to study HSC transplantation and cellular therapies. A secondary purpose of the Research Database is to have a comprehensive source of data to study marrow toxic injuries. Objectives: To learn more about what makes stem cell transplants and cellular therapies work well such as: - Determine how well recipients recover from their transplants or cellular therapy; - Determine how recovery after a transplant or cellular therapy can be improved; - Determine how a donor's or recipient's genetics impact recipient recovery after a transplant or cellular therapy; - Determine how access to transplant or cellular therapy for different groups of patients can be improved; - Determine how well donors recover from the collection procedures.

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  • Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors Recruiting

    This randomized phase III trial studies how well standard-dose combination chemotherapy works compared to high-dose combination chemotherapy and stem cell transplant in treating patients with germ cell tumors that have returned after a period of improvement or did not respond to treatment. Drugs used in chemotherapy, such as paclitaxel, ifosfamide, cisplatin, carboplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim or pegfilgrastim, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. It is not yet known whether high-dose combination chemotherapy and stem cell transplant are more effective than standard-dose combination chemotherapy in treating patients with refractory or relapsed germ cell tumors.

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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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  • A Phase 2 Trial of Rituximab and Corticosteroid Therapy for Newly Diagnosed Chronic Graft Versus Host Disease Not Recruiting

    The addition of rituximab to prednisone for the initial treatment of chronic GVHD will increase the overall response rate, enable a more rapid and effective steroid taper.

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

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  • A Phase 3 Study of Brentuximab Vedotin (SGN-35) in Patients at High Risk of Residual Hodgkin Lymphoma Following Stem Cell Transplant (The AETHERA Trial) Not Recruiting

    This is a randomized, double-blind, placebo-controlled, multicenter phase 3 trial to evaluate the efficacy and safety of brentuximab vedotin (SGN-35) and best supportive care (BSC) compared to placebo and BSC in treatment of residual Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT).

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Robeson, (650) 725 - 1647.

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  • A Pilot Study of Imatinib Mesylate in Steroid Refractory Chronic Graft Versus Host Disease Not Recruiting

    To determine if subjects with steroid refractory cGVHD can tolerate imatinib mesylate and whether their cGVHD responds to imatinib mesylate.

    Stanford is currently not accepting patients for this trial. For more information, please contact Joanne Otani, (650) 721 - 2372.

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  • Acute Graft-versus-Host Disease Treatment (BMT CTN 0802) Not Recruiting

    The study is a Phase III, randomized double blind, placebo controlled, and trial evaluating the addition of Mycophenolate mofetil (MMF) vs. placebo to systemic corticosteroids as initial therapy for acute Graft Vs Host Disease (GVHD). The primary endpoint will be GVHD free survival at Day 56 post randomization.

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

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  • Allo BMT in Advanced Leukemia or High Grade Lymphoma Not Recruiting

    To evaluate the role of ablative allogeneic hematopoietic cell transplantation in the treatment of advanced leukemia or lymphoma.

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

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  • Allo vs Hypomethylating/Best Supportive Care in MDS (BMT CTN 1102) Not Recruiting

    This study is designed as a multicenter trial, with biological assignment to one of two study arms; Arm 1: Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT), Arm 2: Non-Transplant Therapy/Best Supportive Care.

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

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

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

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

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  • Allogeneic Transplantation for Patients With Acute Leukemia or Chronic Myelogenous Leukemia (CML) Not Recruiting

    The purpose of the study is to evaluate the overall and disease free survival of recipients who have received G-CSF mobilized stem cells from HLA matched sibling donors.

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

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  • Allogeneic Transplantation From Related Haploidentical Donors Not Recruiting

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

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

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

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

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

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  • Autologous Bone Marrow Transplantation in Acute Non-Lymphoblastic Leukemia During First or Subsequent Remission Not Recruiting

    Evaluate the role of high dose chemotherapy with autologous hematopoietic cell transplantation for AML.

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

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

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

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

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  • Autologous Stem Cell Rescue for Primary Amyloidosis Not Recruiting

    To evaluate the role of high dose therapy and autologous hematopoietic cell transplant for amyloidosis.

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

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  • Blood and Marrow Transplant Clinical Research Network Not Recruiting

    The purpose of this network is to accelerate research in hematopoietic stem cell transplantation by comparing novel therapies to existing ones.

    Stanford is currently not accepting patients for this trial.

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  • CD8+ Memory T-Cells as Consolidative Therapy After Donor Non-myeloablative Hematopoietic Cell Transplant in Treating Patients With Leukemia or Lymphoma Not Recruiting

    This phase II trial studies how well cluster of differentiation 8 (CD8)+ memory T-cells work as a consolidative therapy following a donor non-myeloablative hematopoietic cell transplant in treating patients with leukemia or lymphoma. Giving total lymphoid irradiation and anti-thymocyte globulin before a donor hematopoietic cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of the donor's white blood cells, such as CD8+ memory T-cells, may boost this effect and may be an effective treatment to kill any cancer cells that may be left in the body (consolidative therapy).

    Stanford is currently not accepting patients for this trial. For more information, please contact Leah Galvez, 650-725-7951.

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  • Chronic Graft-versus-Host Disease Treatment (BMT CTN 0801) Not Recruiting

    This study is designed as a combined Phase II/III, randomized, open label, multicenter, prospective comparative study of sirolimus plus prednisone versus sirolimus/calcineurin-inhibitor plus prednisone for the treatment of chronic GVHD. Patients will be stratified by transplant center and will be randomized to an experimental arm of one of the two pre-specified experimental arms (sirolimus + prednisone or the comparator arm of sirolimus + calcineurin inhibitor + prednisone) in a 1:1 ratio.

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

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  • Cyclosporine Eye Drops in Preventing Graft-Versus-Host Disease of the Eye in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer or Bone Marrow Failure Disorder Not Recruiting

    RATIONALE: Cyclosporine eye drops may prevent graft-versus-host disease of the eye in patients who have undergone donor stem cell transplant for hematologic cancer or bone marrow failure disorder. PURPOSE: This randomized phase I trial is studying how well cyclosporine eye drops work in preventing graft-versus-host disease of the eye in patients who have undergone donor stem cell transplant for hematologic cancer or bone marrow failure disorder.

    Stanford is currently not accepting patients for this trial. For more information, please contact Joanne Otani, (650) 721 - 2372.

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  • Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study Not Recruiting

    Single arm, open-label study to provide Defibrotide to patients diagnosed with VOD. Defibrotide is no longer available though the Emergency Use IND mechanism (also known as compassionate use, or single patient named use). This protocol is the only mechanism by which Defibrotide can be made available to patients in the U.S.

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

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  • Defibrotide for the Treatment of Severe Hepatic Veno-Occlusive Disease in Hematopoetic Stem Cell Transplant Patients Not Recruiting

    The purpose of this study is to (1) demonstrate the efficacy and safety (toxicity) of 25 mg/kg/day of Defibrotide in patients with severe veno-occlusive disease (sVOD) and (2) evaluate serum and endothelial markers of veno-occlusive disease (VOD) through the analysis of blood samples.

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

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  • Donor Atorvastatin Treatment for Preventing Severe Acute Graft-Versus-Host Disease in Patients Undergoing Myeloablative Peripheral Blood Stem Cell Transplantation Not Recruiting

    This phase II trial studies donor atorvastatin treatment for the prevention of severe acute graft-versus-host disease (GVHD) in patients undergoing myeloablative peripheral blood stem cell (PBSC) transplantation. Giving chemotherapy and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also prevent the patient's immune system reject the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving atorvastatin to the donor before transplant may prevent this from happening.

    Stanford is currently not accepting patients for this trial. For more information, please contact Leah Galvez, 650-725-7951.

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  • Donor Regulatory T Cells in Treating Patients With Visceral Acute Graft-versus-Host Disease After Stem Cell Transplant Not Recruiting

    This phase I trial studies the side effects and best dose of donor regulatory T cells in treating patients with graft-versus-host disease affecting the liver or gastrointestinal organs (visceral) within 100 days (acute) after undergoing a stem cell transplant. Graft-versus-host disease occurs when donor immune cells infused in a stem cell transplant attack the gut, skin, liver, or other organ systems of the patient. Regulatory T cells are a type of immune cell that may be able to reduce the attack of the donor's immune cells on the patient's normal cells and help treat graft-vs-host disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Joanne Otani, 650-721-2372.

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  • Double Cord Versus Haploidentical (BMT CTN 1101) Not Recruiting

    Hematopoietic cell transplants (HCT)are one treatment option for people with leukemia or lymphoma. Family members,unrelated donors or banked umbilical cordblood units with similar tissue type can be used for HCT. This study will compare the effectiveness of two new types of bone marrow transplants in people with leukemia or lymphoma: one that uses bone marrow donated from family members with only partially matched bone marrow; and, one that uses two partially matched cord blood units.

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

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

    This is a phase 2 study of gemcitabine + high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue for Hodgkin's Disease

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

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  • Haploid Allogeneic Transplant Using the CliniMACS System Not Recruiting

    To assess the proportion of patients with donor neutrophil engraftment within 30 days of allogeneic transplant. To assess the incidence of acute GvHD during the first 100 days after transplantation.

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

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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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  • High Dose Sequential Therapy and Autologous Stem Cell Rescue for Multiple Myeloma Not Recruiting

    To assess the role of autologous hematopoietic cell rescue in the treatment of multiple myeloma.

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

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  • High-Dose Sequential Therapy and Single Autologous Transplantation for Multiple Myeloma Not Recruiting

    This study uses a sequence of high-dose chemotherapy drugs and a stem cell transplant to treat multiple myeloma. The study is being performed to evaluate the efficacy and side effects of treatment. Specifically, the study is designed to reduce the risk of interstitial pneumonitis.

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

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  • Ibrutinib in Combination With Corticosteroids vs Placebo in Combination With Corticosteroids in Subjects With New Onset cGVHD Not Recruiting

    To evaluate the safety and efficacy of ibrutinib in combination with prednisone in subjects with newly diagnosed moderate to severe cGVHD.

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

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  • Ibrutinib in Treating Patients With Refractory or Relapsed Lymphoma After Donor Stem Cell Transplant Not Recruiting

    This phase II trial studies how well ibrutinib works in treating patients after a donor stem cell transplant for lymphoma that is not responding to treatment or has come back. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

    Stanford is currently not accepting patients for this trial.

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  • Imatinib and Rituximab in Treating Cutaneous Sclerosis in Patients With Chronic Graft-Versus-Host Disease Not Recruiting

    This randomized phase II trial is evaluating how well imatinib mesylate works compared to rituximab in treating cutaneous sclerosis in patients with chronic graft- versus-host disease (GVHD). Both imatinib and rituximab have been reported to decrease skin thickening and improve skin and joint flexibility in people with cutaneous sclerosis due to chronic GVHD.

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

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  • Immune Mediated Disorders After Allogeneic Hematopoietic Cell Transplantation Not Recruiting

    The purpose of this research study is to better understand the onset and course of graft versus host disease (GVHD)and other immune-mediated disorders after stem cell transplant.

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

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  • Intravenous Administration of RGI-2001 in Patient Undergoing Allogenic Hematopoietic Stem Cell Transplantation (AHSCT) Not Recruiting

    The clinical trial is a Phase 1/2a, open-label, multi-center, dose-escalation study to evaluate the safety, tolerability and pharmacokinetic profile of RGI-2001 in patients undergoing AHSCT, with radiation or non-radiation myeloablative preparative treatment. The study will be separated into two parts; a dose escalation phase to assess safety, followed by a large expansion phase to further evaluate the pharmacologic effects of either a Maximum Tolerated Dose, Maximum Feasible Dose or optimal pharmacologically active dose of RGI-2001. The initial dose escalation safety portion of the study (Part 1) will include higher risk patients and limit the unrelated donor transplants. After safety is established in part 1 of the study, the second portion of the study will expand the enrollment criteria and allow transplantation by either related or unrelated donors. This study will endeavor to identify the dose range at which RGI-2001 has an acceptable safety profile, at which biologic activity is observed, and to guide possible dose levels to utilize in later phase studies based on biological activity.

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

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  • Mixed Chimera Allogeneic Transplantation From Matched Unrelated Donors For The Treatment Of Multiple Myeloma Not Recruiting

    The purpose of the study is to determine the toxicity and feasibility of non-myeloablative allogeneic hematopoietic cell transplants for multiple myeloma from unrelated donors.

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

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  • Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With ALL or CML Not Recruiting

    This phase I/II trial is studying the side effects and best way to give nilotinib when given alone or sequentially after imatinib mesylate after donor stem cell transplant in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia. Nilotinib and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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

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  • Non-Myeloablative Allogeneic Transplant for Myelodysplastic Syndromes and Myeloproliferative Disorders Not Recruiting

    To improve survival outcomes for patients with MDS and MPD with a nonmyeloablative allogeneic hematopoietic cell transplant.

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

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  • Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma Not Recruiting

    Mixed chimerism transplantation is an approach to allogeneic transplants that attempts to decrease regimen-related toxicity by using non-myeloablative preparatory regimens; establish mixed chimerism using low dose total body irradiation along with immunosuppression using cyclosporine and mycophenolate mofetil; suppress graft-vs-host and host-vs-graft reactions to allow a mixed chimeric state to be established, encourage tolerance and prevent graft-vs-host disease (GvHD) during the mixed chimerism period and use donor lymphocyte infusions to convert the patient to a full chimera while developing a graft-vs-tumor effect.

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

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  • Peripheral Blood Stem Cell Transplant vs Bone Marrow Transplant in Individuals With Hematologic Cancers (BMT CTN 0201) Not Recruiting

    The study is designed as a Phase III, randomized, open label, multicenter, prospective, comparative trial of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) versus marrow from unrelated donors for transplantation in patients with hematologic malignancies. Recipients will be stratified by transplant center and disease risk and will be randomized to either the PBSC or marrow arm in a 1:1 ratio.

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

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  • Ph II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma Not Recruiting

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

    Stanford is currently not accepting patients for this trial. For more information, please contact Michelle Chin, 650-721-4183.

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  • Phase 1 Infused Donor T Regulatory Cells in Steroid Dependent/Refractory Chronic GVHD Not Recruiting

    Chronic graft versus host disease (cGVHD) is a common complication of bone marrow or hematopoietic cell transplant from another person (allogeneic transplant). This study will determine if subjects with steroid dependent/refractory cGVHD can tolerate infusion of donor regulatory T cells and whether their cGVHD responds to the infusion.

    Stanford is currently not accepting patients for this trial. For more information, please contact Joanne Otani, 650-721-2372.

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  • Phase 1 Nilotinib in Steroid Dependent/Refractory Chronic Graft Versus Host Disease Not Recruiting

    PRIMARY OBJECTIVES: Determine the safety and tolerability of nilotinib in steroid dependent / refractory cGVHD. SECONDARY OBJECTIVES: Determine the clinical efficacy of nilotinib in steroid dependent / refractory cGVHD.

    Stanford is currently not accepting patients for this trial. For more information, please contact Joanne Otani, 650-721-2372.

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  • Phase 2 Poor Risk DLBCL of TLI and ATG Followed by Matched Allogeneic HT as Consolidation to Autologous HCT Not Recruiting

    The purpose of this study is to determine if double autologous then allogeneic hematopoietic cell transplant may offer an improved treatment option for patients with relapsed diffuse large B-cell lymphoma (DLBCL) 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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  • Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using TLI & ATG Not Recruiting

    To evaluate the toxicity and tolerability of this tandem autologous/allogeneic transplant approach for patients with advanced stage multiple myeloma.

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

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

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

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

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  • Phase II Early Behavioral Intervention in BMT w/ Sleep Disturbance-Assess QOL+Fatigue+Cognitive f(x) Not Recruiting

    This pilot clinical trial studies early brief behavioral intervention in treating sleep disturbance and improving quality of life in patients undergoing bone marrow transplant (BMT). A brief behavioral intervention may reduce symptoms of insomnia and fatigue and improve quality of life and cognitive function in patients undergoing BMT

    Stanford is currently not accepting patients for this trial. For more information, please contact Oxana Palesh, 650-725-7011.

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  • Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders Not Recruiting

    Allogeneic stem cell transplantation (transplant of blood cells from another individual) is a treatment option for patients with myelodysplasia or myeloproliferative Disorders. During the course of this study, it will be evaluated whether a particular type of blood cell, called a cytokine-induced killer (CIK) cell, may add benefit to allogeneic stem cell transplantation. CIK cells are present in small quantities in the bloodstream but their numbers can be expanded after a brief period of nurturing in a laboratory.

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

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  • Post-transplant Autologous Cytokine-induced Killer (CIK) Cells for Treatment of High Risk Hematologic Malignancies Not Recruiting

    The purpose of the study is to conduct a phase I study of adoptive immunotherapy with autologous, ex-vivo expanded cytokine-induced killer (CIK) cells to reduce the relapse rate in autologous stem cell transplant patients with high-risk hematologic malignancies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sherry Moore, (650) 725 - 7951.

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  • Prophylactic Use of Maribavir for the Prevention of Cytomegalovirus (CMV) Disease in Stem Cell Transplant Recipients Not Recruiting

    The purpose of this research study is to investigate whether or not maribavir is safe and effective for preventing CMV disease when taken by mouth for up to 12 weeks in patients who have had a stem cell transplant.

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

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  • Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Adults With Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Not Recruiting

    The primary objective of phase 1 is to evaluate the safety of KTE-C19 and atezolizumab combination regimens. The primary objective of phase 2 is to evaluate the efficacy of KTE-C19 and atezolizumab, as measured by complete response rate in participants with refractory diffuse large B-cell lymphoma (DLBCL).

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

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  • Sibling and Unrelated Donor Hematopoietic Cell Transplant in Hematologic Malignancies Not Recruiting

    The purpose of this study is to determine the tolerability and efficacy in treating patients aged 51-60 with acute leukemia and in treating myelodysplastic syndromes (MDS) or myeloproliferative disorders (MPD).

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

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  • Sirolimus & Mycophenolate Mofetil as GvHD Prophylaxis in Myeloablative, Matched Related Donor HCT Not Recruiting

    A continuation study of sirolimus and mycophenolate mofetil (MMF) for graft-vs-host disease (GvHD) prophylaxis for patients undergoing matched related allogeneic hematopoietic stem cell transplantation (HSCT) for acute and chronic leukemia, myelodysplastic syndrome (MDS), high risk non-Hodgkin lymphoma (NHL), or Hodgkin lymphoma (HL)

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

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  • Sirolimus and Mycophenolate Mofetil as Graft Versus Host Disease Prophylaxis in Myeloablative Matched Related Donor Hematopoietic Cell Transplant Not Recruiting

    To evaluate the incidence of grade II-IV acute GVHD with sirolimus and mycophenolate mofetil GVHD prophylaxis.

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

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  • Sirolimus as Primary Therapy for the Treatment of Chronic Graft Versus Host Disease Not Recruiting

    Evaluate the clinical activity of sirolimus in combination with cyclosporine and corticosteroids as first line therapy for the treatment of chronic Graft Versus Host Disease.

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

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  • Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease Not Recruiting

    To study the effectiveness of an immunosuppressive drug sirolimus, in the treatment of chronic graft versus host disease in combination with prednisone.

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

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  • Sirolimus/Tacrolimus Versus Tacrolimus/Methotrexate for Preventing Graft-Versus-Host Disease (GVHD) (BMT CTN 0402) Not Recruiting

    The study is designed as a phase III, randomized, open label, multicenter, prospective, comparative trial of sirolimus and tacrolimus versus tacrolimus and methotrexate as graft-versus-host disease (GVHD) prophylaxis after human leukocyte antigen (HLA)-matched, related, peripheral blood stem cell transplantation in individuals with hematologic cancer. Participants will be stratified by transplant center and will be randomly assigned to the sirolimus/tacrolimus or tacrolimus/methotrexate arms at a 1:1 ratio.

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

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  • Stem Cell Transplant From Matched Unrelated or Partially Matched Related Donors Not Recruiting

    To evaluate the use of unrelated donors for hematopoietic cell transplantation in the treatment of hematologic and lymphoid malignancies.

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

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  • Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma (BMT CTN 0702) Not Recruiting

    The study is designed as a Phase III, multicenter trial of tandem autologous transplants plus maintenance therapy versus the strategy of single autologous transplant plus consolidation therapy with lenalidomide, bortezomib and dexamethasone (RVD) followed by maintenance therapy or single autologous transplant plus maintenance therapy as part of upfront treatment of multiple myeloma (MM). Lenalidomide will be used as maintenance therapy for three years in all arms.

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

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  • Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Chronic Graft Versus Host Disease Not Recruiting

    The purpose of this study is to assess the safety and clinical efficacy of ibrutinib in subjects with steroid dependent or refractory Chronic Graft Versus Host Disease.

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

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  • Study of US-ATG-F to Prevent Chronic Graft Versus Host Disease (GVHD) Not Recruiting

    The study objective is to compare the efficacy and safety of US-ATG-F as a supplement to standard of care prophylaxis versus standard of care prophylaxis alone in moderate to severe chronic GVHD-free survival.

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

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  • Targeted Therapy of Bronchiolitis Obliterans Syndrome Not Recruiting

    This phase II trial studies how well giving fluticasone propionate, azithromycin, and montelukast sodium (FAM) together works in treating patients with bronchiolitis obliterans who previously underwent stem cell transplant. FAM may be an effective treatment for bronchiolitis obliterans

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

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

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

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

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  • Transplantation for Patients With Chronic Lymphocytic Leukemia Not Recruiting

    To evaluate the role of high dose therapy and autologous or allogeneic hematopoietic cell transplantation for the treatment of chronic lymphocytic leukemia.

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

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  • Trial to Evaluate Palifermin in the Reduction of Acute Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Allogeneic Marrow/Peripheral Blood Progenitor Cell (PBPC) Transplantation Not Recruiting

    The main purpose of this study is to evaluate the effect of palifermin versus placebo in the reduction of severe acute graft versus host disease (GVHD) and severe oral mucositis.

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

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Teaching

2019-20 Courses


Publications

All Publications


  • Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT) BONE MARROW TRANSPLANTATION Kansagra, A. J., Frey, N. V., Bar, M., Laetsch, T. W., Carpenter, P. A., Savani, B. N., Heslop, H. E., Bollard, C. M., Komanduri, K. V., Gastineau, D. A., Chabannon, C., Perales, M. A., Hudecek, M., Aljurf, M., Andritsos, L., Barrett, J. A., Bachanova, V., Bonini, C., Ghobadi, A., Gill, S. I., Hill, J. A., Kenderian, S., Kebriaei, P., Nagler, A., Maloney, D., Liu, H. D., Shah, N. N., Kharfan-Dabaja, M. A., Shpall, E. J., Mufti, G. J., Johnston, L., Jacoby, E., Bazarbachi, A., DiPersio, J. F., Pavletic, S. Z., Porter, D. L., Grupp, S. A., Sadelain, M., Litzow, M. R., Mohty, M., Hashmi, S. K. 2019; 54 (11): 1868?80
  • Hematopoietic Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Updated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation DeFilipp, Z., Advani, A. S., Bachanova, V., Cassaday, R. D., Deangelo, D. J., Kebriaei, P., Rowe, J. M., Seftel, M. D., Stock, W., Tallman, M. S., Fanning, S., Inamoto, Y., Kansagra, A., Johnston, L., Nagler, A., Sauter, C. S., Savani, B. N., Perales, M., Carpenter, P. A., Larson, R. A., Weisdorf, D. 2019

    Abstract

    The role of hematopoietic cell transplantation (HCT) for adults with acute lymphoblastic leukemia (ALL) is reviewed and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of ALL experts developed consensus on the treatment recommendations based upon the evidence. Allogeneic HCT offers a survival benefit in selected patients with ALL and this review summarizes the standard indications as well as the areas of controversy. There is now greater experience with pediatric-inspired chemotherapy regimens that has transformed upfront therapy for adult ALL, resulting in higher remission rates and overall survival. This in turn has increased the equipoise around decision-making for ALL in first complete remission (CR1) when there is no measurable residual disease (MRD) at the end of induction and/or consolidation. Randomized studies are needed for adults with ALL to compare allogeneic HCT in CR1 with pediatric-inspired chemotherapy alone. Studies to assess indications for transplant in the evolving landscape of MRD assessments and novel targeted and immune therapeutics remain important areas of investigation.

    View details for DOI 10.1016/j.bbmt.2019.08.014

    View details for PubMedID 31446198

  • Transplantation of donor grafts with defined ratio of conventional and regulatory T cells in HLA-matched recipients JCI INSIGHT Meyer, E. H., Laport, G., Xie, B. J., MacDonald, K., Heydari, K., Sahaf, B., Tang, S., Baker, J., Armstrong, R., Tate, K., Tadisco, C., Arai, S., Johnston, L., Lowsky, R., Muffly, L., Rezvani, A. R., Shizuru, J., Weng, W., Sheehan, K., Miklos, D., Negrin, R. S. 2019; 4 (10)
  • Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT). Bone marrow transplantation Kansagra, A. J., Frey, N. V., Bar, M., Laetsch, T. W., Carpenter, P. A., Savani, B. N., Heslop, H. E., Bollard, C. M., Komanduri, K. V., Gastineau, D. A., Chabannon, C., Perales, M. A., Hudecek, M., Aljurf, M., Andritsos, L., Barrett, J. A., Bachanova, V., Bonini, C., Ghobadi, A., Gill, S. I., Hill, J. A., Kenderian, S., Kebriaei, P., Nagler, A., Maloney, D., Liu, H. D., Shah, N. N., Kharfan-Dabaja, M. A., Shpall, E. J., Mufti, G. J., Johnston, L., Jacoby, E., Bazarbachi, A., DiPersio, J. F., Pavletic, S. Z., Porter, D. L., Grupp, S. A., Sadelain, M., Litzow, M. R., Mohty, M., Hashmi, S. K. 2019

    Abstract

    On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

    View details for PubMedID 31092900

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

    Abstract

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

    View details for DOI 10.1182/bloodadvances.2019000297

    View details for PubMedID 31427277

  • Transplantation of donor grafts with defined ratio of conventional and regulatory T cells in HLA-matched recipients. JCI insight Meyer, E. H., Laport, G., Xie, B. J., MacDonald, K., Heydari, K., Sahaf, B., Tang, S. W., Baker, J., Armstrong, R., Tate, K., Tadisco, C., Arai, S., Johnston, L., Lowsky, R., Muffly, L., Rezvani, A. R., Shizuru, J., Weng, W. K., Sheehan, K., Miklos, D., Negrin, R. S. 2019; 4 (10)

    Abstract

    BACKGROUNDIn preclinical murine and early clinical studies of hematopoietic cell transplantation, engineering of donor grafts with defined ratios of CD4+CD25+FoxP3+ Tregs to conventional T cells (Tcons) results in the prevention of graft-versus-host disease and improved immune reconstitution. The use of highly purified primary graft Tregs for direct cell infusion has potential advantages over impure immunomagnetic selection or culture expansion, but has not been tested clinically. We performed a phase I study of the timed addition of CD34-selected hematopoietic stem cells and Tregs, followed by Tcons for the treatment of patients with high-risk hematological malignancies.METHODSWe present interim evaluation of a single-center open phase I/II study of administration of human leukocyte-matched Tregs and CD34-selected hematopoietic cells, followed by infusion of an equal ratio of Tcons in adult patients undergoing myeloablative hematopoietic stem cell transplantation (HCT) for high-risk or active hematological malignancies. Tregs were purified by immunomagnetic selection and high-speed cell sorting.RESULTSHere we report results for the first 12 patients who received Tregs of between 91% and 96% purity. Greater than grade II GVHD was noted in 2 patients in the first cohort of 5 patients, who received cryopreserved Tregs, but neither acute nor chronic GVHD was noted in the second cohort of 7 patients, who received fresh Tregs and single-agent GVHD prophylaxis. Patients in the second cohort appeared to have normal immune reconstitution compared with patients who underwent transplantation and did not develop GVHD.CONCLUSIONOur study shows that the use of highly purified fresh Tregs is clinically feasible and supports continued investigation of the strategy.TRIAL REGISTRATIONClinicalTrials.gov NCT01660607.FUNDINGNIH NHBLI R01 HL114591 and K08HL119590.

    View details for PubMedID 31092732

  • ASBMT Statement on Routine Prophylaxis for Central Nervous System Recurrence of Acute Lymphoblastic Leukemia following Allogeneic Hematopoietic Cell Transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Sauter, C. S., DeFilipp, Z., Inamoto, Y., Johnston, L., Nagler, A., Savani, B. N., Carpenter, P. A., Perales, M. 2018

    Abstract

    Hematologic malignancies treated with allogeneic hematopoietic cell transplantation (allo-HCT) have varying incidences of posttransplant central nervous system (CNS) relapse, with acute lymphoblastic leukemia (ALL) representing the most common disease histology. While data supporting posttransplant CNS prophylaxis for ALL in the pre-CNS penetrant systemic therapy-era established this as standard practice, controversy exists regarding the role of posttransplant CNS prophylaxis in the contemporary era. Herein we review the most relevant, albeit exclusively retrospective, literature to date for the role of posttransplant CNS prophylaxis in ALL. Given the paucity of data supporting the routine practice of posttransplant CNS prophylaxis for ALL in the contemporary era, this position statement is anticipated to further stoke controversy and discussion within the transplantation community. Ultimately, only well-designed prospective clinical studies will elucidate the role of routine posttransplant CNS prophylaxis.

    View details for PubMedID 30590125

  • Clinical utilization of Chimeric Antigen Receptors T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL) - an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT). Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Kansagra, A. J., Frey, N. V., Bar, M., Laetsch, T. W., Carpenter, P. A., Savani, B. N., Heslop, H. E., Bollard, C. M., Komanduri, K. V., Gastineau, D. A., Chabannon, C., Perales, M. A., Hudecek, M., Aljurf, M., Andritsos, L., Barrett, J. A., Bachanova, V., Bonini, C., Ghobadi, A., Gill, S. I., Hill, J., Kenderian, S., Kebriaei, P., Nagler, A., Maloney, D., Liu, H. D., Shah, N. N., Kharfan-Dabaja, M. A., Shpall, E. J., Mufti, G. J., Johnston, L., Jacoby, E., Bazarbachi, A., DiPersio, J. F., Pavletic, S. Z., Porter, D. L., Grupp, S. A., Sadelain, M., Litzow, M. R., Mohty, M., Hashmi, S. K. 2018

    Abstract

    On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor - T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

    View details for PubMedID 30576834

  • Nonmyeloablative Allogeneic Transplantation Using TLI-ATG Conditioning for Lymphoid and Myeloid Malignancies: Mature Follow-up from a Large, Single Institution Cohort Spinner, M. A., Kennedy, V. E., Tamaresis, J. S., Lavori, P. W., Elder, L. V., Arai, S., Johnston, L. J., Meyer, E. H., Miklos, D. B., Muffly, L. S., Negrin, R. S., Rezvani, A. R., Shizuru, J. A., Weng, W., Hoppe, R. T., Strober, S., Lowsky, R. AMER SOC HEMATOLOGY. 2018
  • Elevated Axicabtagene Ciloleucel (CAR-19) Expansion By Immunophenotyping Is Associated with Toxicity in Diffuse Large B-Cell Lymphoma Spiegel, J. Y., Sahaf, B., Hossain, N., Frank, M. J., Claire, G., Abramian, M., Latchford, T., Villa, B., Cancilla, J., Oak, J., Natkunam, Y., Long, S. R., Arai, S., Johnston, L. J., Lowsky, R., Meyer, E. H., Muffly, L. S., Negrin, R. S., Rezvani, A. R., Shizuru, J. A., Weng, W., Kong, K. A., Mackall, C. L., Miklos, D. B. AMER SOC HEMATOLOGY. 2018
  • Effect of Antihuman T Lymphocyte Globulin on Immune Recovery after Myeloablative Allogeneic Stem Cell Transplantation with Matched Unrelated Donors: Analysis of Immune Reconstitution in a Double-Blind Randomized Controlled Trial BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Gooptu, M., Kim, H. T., Chen, Y., Rybka, W., Artz, A., Boyer, M., Johnston, L., McGuirk, J., Shea, T. C., Jagasia, M., Shaughnessy, P. J., Reynolds, C. G., Fields, M., Alyea, E. P., Ho, V. T., Glavin, F., Dipersio, J. F., Westervelt, P., Ritz, J., Soiffer, R. J. 2018; 24 (11): 2216?23

    Abstract

    We recently conducted a randomized double-blind study in which we demonstrated that moderate/severe chronic graft-versus-host disease (cGVHD) but not cGVHD-free survival was reduced in patients receiving anti-T lymphocyte globulin (ATLG) versus placebo. In a companion study we performed immunophenotypic analysis to determine the impact of ATLG on immune reconstitution (IR) and to correlate IR with clinical outcomes. The randomized study (n?=?254) included patients (aged 18 to 65 years) who underwent myeloablative transplants for acute myeloid leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia from HLA-matched unrelated donors. Ninety-one patients consented for the companion IR study (ATLG?=?44, placebo?=?47). Blood samples were collected on days 30, 100, 180, and 360 after hematopoietic cell transplantation (HCT), and multiparameter flow cytometry was performed in a blinded fashion. Reconstitution of CD3+ and CD4+ T cells was delayed up to 6 months post-HCT in the ATLG arm, whereas absolute regulatory T cell (Treg) (CD4+25+127-) numbers were lower only in the first 100 days. Analysis of the CD4+ Treg and conventional T cells (Tconv) (CD4+25-127+) compartments showed a profound absence of naive Tregs and Tconv in the first 100 days post-HCT, with very slow recovery for 1 year. B cell and natural killer cell recovery were similar in each arm. Higher absolute counts of CD3+, CD4+, CD8+ T, Tregs, and Tconv were associated with improved overall survival, progression-free survival, and nonrelapse mortality but not moderate/severe cGVHD. Although ATLG delays CD3+ and CD4+ T cell recovery post-transplant, it has a relative Treg sparing effect after the early post-HCT period, with possible implications for protection from cGVHD. ATLG severely compromises the generation of naive CD4+ cells (Treg and Tconv), potentially affecting the diversity of the TCR repertoire and T cell responses against malignancy and infection.

    View details for PubMedID 30006305

  • A phase II/III randomized, multicenter trial of prednisone/sirolimus versus prednisone/sirolimus/calcineurin inhibitor for the treatment of chronic graft-versus-host disease: BMT CTN 0801 HAEMATOLOGICA Carpenter, P. A., Logan, B. R., Lee, S. J., Weisdorf, D. J., Johnston, L., Costa, L. J., Kitko, C. L., Bolanos-Meade, J., Sarantopoulos, S., Alousi, A. M., Abhyankar, S., Waller, E. K., Mendizabal, A., Zhu, J., O'Brien, K. A., Lazaryan, A., Wu, J., Nemecek, E. R., Pavletic, S. Z., Cutler, C. S., Horowitz, M. M., Arora, M., BMT CTN 2018; 103 (11): 1915?24

    Abstract

    Initial therapy of chronic graft-versus-host disease is prednisone ± a calcineurin-inhibitor, but most patients respond inadequately. In a randomized, adaptive, phase II/III, multicenter trial we studied whether prednisone/sirolimus or prednisone/sirolimus/photopheresis was more effective than prednisone/sirolimus/calcineurin-inhibitor for treating chronic graft-versus-host disease in treatment-naïve or early inadequate responders. Primary endpoints of this study were proportions of subjects alive without relapse or secondary therapy with 6-month complete or partial response in phase II, or with 2-year complete response in phase III. The prednisone/sirolimus/photopheresis arm closed prematurely because of slow accrual and the remaining two-drug versus three-drug study ended in phase II due to statistical futility with 138 evaluable subjects. The two-drug and three-drug arms did not differ in rates of 6-month complete or partial response (48.6% versus 50.0%, P=0.87), or 2-year complete response (14.7% versus 15.5%, P=0.90). Serum creatinine values >1.5 times baseline were less frequent in the calcineurin-inhibitor-free arm at 2 months (1.5% versus 11.7%, P=0.025) and 6 months (7.8% versus 24.0%, P=0.016). Higher adjusted Short Form-36 Physical Component Summary and Physical Functioning scores were seen in the two-drug arm at both 2 months (P=0.02 and P=0.04, respectively) and 6 months (P=0.007 and P=0.001, respectively). Failure-free survival and overall survival rates at 2 years were similar for patients in the the two-drug and three-drug arms (48.6% versus 46.2%, P=0.78; 81.5% versus 74%, P=0.28). Based on similar long-term outcomes, prednisone/sirolimus is a therapeutic alternative to prednisone/sirolimus/calcineurin-inhibitor for chronic graft-versus-host disease, being easier to administer and better tolerated. Clinicaltrials.gov identifier: NCT01106833.

    View details for PubMedID 29954931

  • ASBMT Practice Guidelines Committee Survey on Long-Term Follow-Up Clinics for Hematopoietic Cell Transplant Survivors BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Hashmi, S. K., Lee, S. J., Savani, B. N., Burns, L., Wingard, J. R., Perales, M., Palmer, J., Chow, E., Meyer, E., Marks, D., Mohty, M., Inamoto, Y., Rodriguez, C., Nagler, A., Sauter, C., Komanduri, K., Pidala, J., Hamadani, M., Johnston, L., Shah, N., Shaughnessy, P., Hamilton, B. K., Majhail, N., Kharfan-Dabaja, M. A., Schriber, J., DeFilipp, Z., Tarlock, K. G., Fanning, S., Curtin, P., Rizzo, J., Carpenter, P. A. 2018; 24 (6): 1119?24

    Abstract

    Significant advances in hematopoietic cell transplantation (HCT) have increased the long-term survivorship of its recipients, but because of unique complications arising from radiation and chemotherapy, recipients require lifelong follow-up. To evaluate current survivorship or long-term follow-up (LTFU) clinics specifically for HCT survivors and to evaluate the potential barriers in their establishment, the American Society for Blood and Marrow Transplantation (ASBMT) Practice Guidelines Committee electronically surveyed 200 HCT programs to gather quantitative and qualitative data about models of care. Among 77 programs (38.5%) that responded, 45% indicated presence of an LTFU clinic; however, LTFU care models varied with respect to services provided, specialist availability, type of patients served, and staffing. Among 55% of programs without an LTFU clinic, 100% agreed that allogeneic HCT survivors have unique needs separate from graft-versus-host disease and that complications could arise during the transition of care either from pediatric to adult settings or away from the HCT center. Lack of expertise, logistics, financial issues, and the observation that 84% of individual practitioners prefer to provide survivorship care were the identified obstacles to establishing new LTFU clinics. The ASBMT hopes that policymakers, HCT providers, and institutions will benefit from the results of this survey and recommends that delivering guidelines-driven screening and expert management of late effects is the goal of first-rate HCT survivorship care.

    View details for PubMedID 29608957

  • Infusion of donor-derived CD8(+) memory T cells for relapse following allogeneic hematopoietic cell transplantation BLOOD ADVANCES Muffly, L., Sheehan, K., Armstrong, R., Jensen, K., Tate, K., Rezvani, A. R., Miklos, D., Arai, S., Shizuru, J., Johnston, L., Meyer, E., Weng, W., Laport, G. G., Negrin, R. S., Strober, S., Lowsky, R. 2018; 2 (6): 681?90

    Abstract

    Murine models showed that CD8+CD44hi memory T (TM) cells could eradicate malignant cells without inducing graft-versus-host disease (GVHD). We evaluated the feasibility and safety of infusing freshly isolated and purified donor-derived phenotypic CD8+ TM cells into adults with disease relapse after allogeneic hematopoietic cell transplantation (HCT). Phenotypic CD8 TM cells were isolated after unmobilized donor apheresis using a tandem immunomagnetic selection strategy of CD45RA depletion followed by CD8+ enrichment. Fifteen patients received CD8+ TM cells at escalating doses (1 × 106, 5 × 106, or 10 × 106 cells per kg). Thirteen received cytoreduction before CD8+ TM cell infusion, and 9 had active disease at the time of infusion. Mean yield and purity of the CD8+ TM infusion were 38.1% and 92.8%, respectively; >90% had CD8+ T effector memory phenotype, cytokine expression, and secretion profile. No adverse infusional events or dose-limiting toxicities occurred; GVHD developed in 1 patient (grade 2 liver). Ten patients (67%) maintained or achieved response (7 complete response, 1 partial response, 2 stable disease) for at least 3 months after infusion; 4 of the responders had active disease at the time of infusion. With a median follow-up from infusion of 328 days (range, 118-1328 days), median event-free survival and overall survival were 4.9 months (95% confidence interval [CI], 1-19.3 months) and 19.6 months (95% CI, 5.6 months to not reached), respectively. Collection and enrichment of phenotypic CD8+ TM cells is feasible, well tolerated, and associated with a low incidence of GVHD when administered as a manipulated infusion of donor lymphocytes in patients who have relapsed after HCT. This trial was registered at www.clinicaltrials.gov as #NCT01523223.

    View details for PubMedID 29572391

  • Phase I/II Trial for Patients with Advanced Hematologic Malignancies Undergoing Myeloablative Allogeneic HCT with a T Cell Depleted Graft with Infusion of Conventional T Cells and Regulatory T Cells Meyer, E., Laport, G. G., Tantsura, I., Tang, S., Sahaf, B., Rangarajan, K., Armstrong, R., Tate, K., Tudisco, C., Sheehan, K., Arai, S., Johnston, L., Muffly, L., Lowsky, R., Rezvani, A., Weng, W., Miklos, D., Negrin, R. S. ELSEVIER SCIENCE INC. 2018: S145
  • Anti-Platelet-Derived Growth Factor Receptor Alpha Chain Antibodies Predict for Response to Nilotinib in Steroid-Refractory or -Dependent Chronic Graft-Versus-Host Disease BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Chen, G. L., Carpenter, P. A., Broady, R., Gregory, T. K., Johnston, L. J., Storer, B. E., Beumer, J. H., Qiu, J., Cerda, K., Le, R., Otani, J. M., Liu, H., Ross, M. A., Arai, S., Flowers, M. D., McCarthy, P. L., Miklos, D. B. 2018; 24 (2): 373?80

    Abstract

    Imatinib has clinical activity in chronic graft-versus-host disease (cGVHD), a significant complication of allogeneic hematopoietic cell transplant. Nilotinib is a tyrosine kinase inhibitor that targets the same receptors as imatinib but with different affinities. We tested the hypothesis that nilotinib is safe and has clinical activity in cGVHD. Thirty-three participants were enrolled in a phase I/II dose escalation and dose extension clinical trial of nilotinib for the treatment of steroid-refractory or- dependent cGVHD (ClinicalTrials.gov, NCT01155817). We assessed safety, clinical response, and pretreatment anti-platelet-derived growth factor receptor alpha chain (anti-PDGFRA) antibody levels. The 200-mg dose was identified as the maximum tolerated dose and used for the phase II dose extension study. At 6 months the incidence of failure-free survival (FFS), cGVHD progression, and nilotinib intolerance resulting in its discontinuation was 50%, 23%, and 23%, respectively. cGVHD responses in skin, joints, and mouth were observed at 3 and 6 months based on improvement in respective National Institutes of Health organ severity scores. Pretreatment anti-PDGFRA antibody levels ? .150 optical density as measured by ELISA correlated with longer FFS time (P?

    View details for PubMedID 29051021

  • Heart Rate Variability Markers as Correlates of Survival in Recipients of Hematopoietic Cell Transplantation Oncology nursing forum Scheiber, C., Johnston, L., Packer, M., Gevirtz, R., Edwards, K. S., Palesh, O. 2018; 45 (2): 250?59

    Abstract

    To assess pre-/post-transplantation changes in autonomic tone, as measured by heart rate variability (HRV), among patients undergoing hematopoietic cell transplantation (HCT) and to look at those changes as they relate to post-transplantation survival rates. .Data were derived from a sample of 27 English-speaking patients undergoing allogeneic or autologous HCT at Stanford University. .A survival analysis using the Kaplan-Meier estimator was employed to explore whether increased HRV would enhance survival probabilities over time among patients undergoing HCT..An increased probability of survival was significantly related to increases in two HRV indexes.HRV may be a useful predictor of mortality among patients undergoing HCT. Interventions deliverable by nurses could be used to enhance HRV for patients identified as being at risk for early mortality.

    View details for PubMedID 29466350

  • Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Soiffer, R. J., Kim, H. T., McGuirk, J., Horwitz, M. E., Johnston, L., Patnaik, M. M., Rybka, W., Artz, A., Porter, D. L., Shea, T. C., Boyer, M. W., Maziarz, R. T., Shaughnessy, P. J., Gergis, U., Safah, H., Reshef, R., DiPersio, J. F., Stiff, P. J., Vusirikala, M., Szer, J., Holter, J., Levine, J. D., Martin, P. J., Pidala, J. A., Lewis, I. D., Ho, V. T., Alyea, E. P., Ritz, J., Glavin, F., Westervelt, P., Jagasia, M. H., Chen, Y. 2017: JCO2017758177

    Abstract

    Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

    View details for PubMedID 29040031

  • Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index in Nonmyeloablative Allogeneic Stem Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Veeraputhiran, M., Yang, L., Sundaram, V., Arai, S., Lowsky, R., Miklos, D., Meyer, E., Muffly, L., Negrin, R., Rezvani, A., Shizuru, J., Weng, W., Johnston, L. 2017; 23 (10): 1744?48

    Abstract

    The Hematopoietic Cell Transplantation (HCT)-Specific Comorbidity Index (HCT-CI) has been extensively studied in myeloablative and reduced-intensity conditioning regimens, with less data available regarding the validity of HCT-CI in nonmyeloablative (NMA) allogeneic transplantation. We conducted a retrospective analysis to evaluate the association between HCT-CI and nonrelapse mortality (NRM) and all-cause mortality (ACM) in patients receiving the total lymphoid irradiation and antithymocyte globulin (TLI/ATG) NMA transplantation preparative regimen. We abstracted demographic and clinical data from consecutive patients, who received allogeneic HCT with the TLI/ATG regimen between January 2008 and September 2014, from the Stanford blood and marrow transplantation database. We conducted univariable and multivariable Cox proportional hazards regression models to evaluate the association between HCT-CI and NRM and ACM. In all, 287 patients were included for analysis. The median age of the patients was 61 (range, 22 to 77) years. The median overall survival was 844 (range, 374 to 1484) days. Most patients had Karnofsky performance score of 90 or above (85%). Fifty-two (18%) patients relapsed within 3 months and 108 (38%) patients relapsed within 1 year, with a median time to relapse of 163 (range, 83 to 366) days. Among the comorbidities in the HCT-CI identified at the time of HCT, reduced pulmonary function was the most common (n?=?89), followed by prior history of malignancy (n?=?39), psychiatric condition (n?=?38), and diabetes (n?=?31). Patients with higher HCT-CI scores had higher mortality risks for ACM (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.22 to 3.14 for HCT-CI score 1 or 2 and HR, 1.85; 95% CI, 1.11 to 3.08 for HCT-CI score ??3, compared with 0, respectively). Among individual HCT-CI variables, diabetes (HR, 2.31; 95% CI, 1.79 to 2.89; P?=?.003) and prior solid tumors (HR, 1.75; 95% CI, 1.02 to 3.00; P?=?.043) were associated with a higher risk of ACM. Higher HCT-CI scores were significantly associated with higher risk of death. HCT-CI is a valid tool for predicting ACM in NMA TLI/ATG allogeneic HCT.

    View details for PubMedID 28668491

  • Posttransplant feasibility study of nilotinib prophylaxis for high-risk Philadelphia chromosome positive leukemia BLOOD Carpenter, P. A., Johnston, L., Fernandez, H. F., Radich, J. P., Mauro, M. J., Flowers, M. D., Martin, P. J., Gooley, T. A. 2017; 130 (9): 1170?72

    View details for PubMedID 28698203

  • Increased Foxp3(+)Helios(+) Regulatory T Cells and Decreased Acute Graft-versus-Host Disease after Allogeneic Bone Marrow Transplantation in Patients Receiving Sirolimus and RGI-2001, an Activator of Invariant Natural Killer T Cells BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Chen, Y., Efebera, Y. A., Johnston, L., Ball, E. D., Avigan, D., Lekakis, L. J., Bachier, C. R., Martin, P., Duramad, O., Ishii, Y., Han, S., Jung, Y., Lee, D., Kunkel, L., Negrin, R. S., Bui, J. D. 2017; 23 (4): 625-634

    Abstract

    Regulatory T (Treg) cells play a central role in immune tolerance and prevention of aberrant immune responses. Several studies have suggested that the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) can be ameliorated by increasing Tregs. We have developed an approach of in vivo expansion of Tregs with RGI-2001, a novel liposomal formulation of a synthetic derivative of alpha-galactosylceramide, a naturally occurring ligand that binds to CD1 and activates and expands invariant natural killer cells. In preclinical studies, a single intravenous infusion of RGI-2001 expanded Treg and could ameliorate GVHD in a mouse model of allogeneic HCT. To explore the role of RGI-2001 in clinical HCT, we initiated a phase 2A clinical trial (n?=?29), testing 2 different doses of RGI-2001 administered as a single infusion on day 0 of allogeneic HCT. RGI-2001 was well tolerated and without infusion reactions or cytokine release syndrome. A subset of patients (8 of 29, 28%) responded to RGI-2001 by inducing a markedly increased number of cells with a Treg phenotype. The Treg had a high Ki-67 index and were almost exclusively Helios(+) and Foxp3(+), indicating that their accumulation was due to expansion of natural Treg. Notably, the incidence of grade 2 to 4 GVHD in the 8 patients who responded to RGI-2001 was 12.5%, compared with 52.4% in the 21 patients who did not respond. No grade 3 or 4 GVHD was observed in the responder group, compared with a 9.5% incidence among nonresponders. Immunosuppression with sirolimus was also associated with a low incidence of GVHD, suggesting that RGI-2001 may have synergized with sirolimus to promote Treg expansion.

    View details for DOI 10.1016/j.bbmt.2017.01.069

    View details for Web of Science ID 000397364300013

  • Integrating cancer survivorship care into allogeneic BMT recovery. Bugos, K., Stenger, S., Smith, A., Johnston, L., Gross, M., Knight, G., Lambert, S., Muffly, L. S. AMER SOC CLINICAL ONCOLOGY. 2017
  • HLA-mismatched unrelated donor transplantation using TLI-ATG conditioning has a low risk of GVHD and potent antitumor activity. Blood advances Spinner, M. A., Fernández-Viña, M., Creary, L. E., Quinn, O., Elder, L., Arai, S., Johnston, L. J., Meyer, E. H., Miklos, D. B., Muffly, L. S., Negrin, R. S., Shizuru, J. A., Weng, W. K., Laport, G. G., Strober, S., Lowsky, R., Rezvani, A. R. 2017; 1 (17): 1347?57

    Abstract

    Many patients lack a fully HLA-matched donor for hematopoietic cell transplantation (HCT), and HLA mismatch is typically associated with inferior outcomes. Total lymphoid irradiation and antithymocyte globulin (TLI-ATG) is a nonmyeloablative conditioning regimen that is protective against graft-versus-host disease (GVHD), and we hypothesized that the protective effect would extend beyond HLA-matched donors. We report outcomes for all consecutively transplanted patients at Stanford University from December 2001 through May 2015 who received TLI-ATG conditioning and HCTs from 8 to 9 out of 10 HLA-mismatched unrelated donors (MMUDs, N = 72) compared with 10 out of 10 HLA-matched unrelated donors (MUDs, N = 193). The median age of the patients was 60 years with a median follow-up of 2 years, and there was a similar distribution of lymphoid and myeloid malignancies in both cohorts. There were no significant differences between MMUD and MUD cohorts in overall survival (46% vs 46% at 5 years, P = .86), disease-free survival (38% vs 28% at 5 years, P = .25), nonrelapse mortality (17% vs 12% at 2 years, P = .34), acute GVHD grades III-IV (6% vs 3% at day +100, P = .61), or chronic GVHD (39% vs 35% at 5 years, P = .49). There was a trend toward less relapse in the MMUD cohort (45% vs 60% at 5 years, hazard ratio: 0.71, P = .094), which was significant for patients with lymphoid malignancies (29% vs 57% at 5 years, hazard ratio: 0.55, P = .044). Achieving full donor chimerism was strongly associated with lower relapse rates. TLI-ATG conditioning may overcome the traditionally poorer outcome associated with HLA-mismatched donors and may be particularly well suited for patients with lymphoid malignancies who lack HLA-matched donors.

    View details for PubMedID 29296777

  • Improving Care With a Portfolio of Physician-Led Cancer Quality Measures at an Academic Center Improving Care With a Portfolio of Physician-Led Cancer Quality Measures at an Academic Center Porter, J. B. 2017; 13 (8): e673-e682

    Abstract

    Development and implementation of robust reporting processes to systematically provide quality data to care teams in a timely manner is challenging. National cancer quality measures are useful, but the manual data collection required is resource intensive, and reporting is delayed. We designed a largely automated measurement system with our multidisciplinary cancer care programs (CCPs) to identify, measure, and improve quality metrics that were meaningful to the care teams and their patients.Each CCP physician leader collaborated with the cancer quality team to identify metrics, abiding by established guiding principles. Financial incentive was provided to the CCPs if performance at the end of the study period met predetermined targets. Reports were developed and provided to the CCP physician leaders on a monthly or quarterly basis, for dissemination to their CCP teams.A total of 15 distinct quality measures were collected in depth for the first time at this cancer center. Metrics spanned the patient care continuum, from diagnosis through end of life or survivorship care. All metrics improved over the study period, met their targets, and earned a financial incentive for their CCP.Our quality program had three essential elements that led to its success: (1) engaging physicians in choosing the quality measures and prespecifying goals, (2) using automated extraction methods for rapid and timely feedback on improvement and progress toward achieving goals, and (3) offering a financial team-based incentive if prespecified goals were met.

    View details for DOI 10.1200/JOP.2017.021139

    View details for PubMedCentralID PMC5880618

  • A Prospective Randomized Double Blind Phase 3 Clinical Trial of Anti- T Lymphocyte Globulin (ATLG) to Assess Impact on Chronic Graft-Versus-Host Disease (cGVHD) Free Survival in Patients Undergoing HLA Matched Unrelated Myeloablative Hematopoietic Cell Transplantation (HCT) Soiffer, R. J., Kim, H. T., McGuirk, J., Horwitz, M. E., Johnston, L., Patnaik, M. M., Rybka, W., Artz, A., Porter, D. L., Shea, T. C., Boyer, M. W., Maziarz, R. T., Jagasia, M. H., Shaughnessy, P. J., Gergis, U., Safah, H., Reshef, R., DiPersio, J. F., Stiff, P. J., Vusirikala, M., Szer, J., Holter, J., Levine, J. D., Martin, P. J., Pidala, J. A., Lewis, I. D., Ho, V. T., Alyea, E. P., Ritz, J., Glavin, F., Westervelt, P., Chen, Y. AMER SOC HEMATOLOGY. 2016
  • A Phase I Study of Donor Regulatory T Cells As Treatment for Steroid Dependent/Refractory Chronic Graft Versus Host Disease Johnston, L., Armstrong, R., Baker, J., Sahaf, B., Otani, J., Tate, K., Tudisco, C., Sheehan, K., Meyer, E., Miklos, D., Negrin, R. S. AMER SOC HEMATOLOGY. 2016
  • Phase I Study of CD8 Memory T-Cell Donor Lymphocyte Infusion for Relapse of Hematologic Malignancies Following Matched Related Donor Allogeneic Hematopoietic Cell Transplantation Muffly, L. S., Sheehan, K., Armstrong, R., Tate, K., Tudisco, C., Rezvani, A. R., Miklos, D., Arai, S., Shizuru, J., Johnston, L., Meyer, E., Weng, W., Laport, G. G., Negrin, R. S., Strober, S., Lowsky, R. AMER SOC HEMATOLOGY. 2016
  • Allogeneic Transplants from HLA-Mismatched Unrelated Donors Using Total Lymphoid Irradiation and Antithymocyte Globulin Conditioning Retain a Low Risk of Graft-Versus-Host Disease and Non-Relapse Mortality with at Least As Potent Anti-Tumor Activity As with Matched Unrelated Donors Spinner, M. A., Vina, M., Elder, L., Arai, S., Johnston, L., Meyer, E., Miklos, D., Muffly, L., Negrin, R. S., Shizuru, J., Weng, W., Laport, G. G., Strober, S., Lowsky, R., Rezvani, A. R. AMER SOC HEMATOLOGY. 2016
  • Lung Function Trajectory in Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Cell Transplant ANNALS OF THE AMERICAN THORACIC SOCIETY Cheng, G., Storer, B., Chien, J. W., Jagasia, M., Hubbard, J. J., Burns, L., Ho, V. T., Pidala, J., Palmer, J., Johnston, L., Mayer, S., Crothers, K., Pusic, I., Lee, S. J., Williams, K. M. 2016; 13 (11): 1932?39

    Abstract

    The natural history of lung function in patients with bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplant is poorly characterized. Understanding the trajectory of lung function is necessary for prompt clinical recognition and treatment and also for the rational design of prospective studies.To describe the longitudinal trajectory of lung function parameters, including FEV1, in patients with BOS after hematopoietic cell transplant.Subjects with BOS defined by National Institutes of Health consensus guidelines criteria from a recent multicenter prospective trial of combination treatment with fluticasone, azithromycin and montelukast and a retrospective cohort from Fred Hutchinson Cancer Research Center were included. Longitudinal change in FEV1 for each patient was calculated on the basis of available pulmonary function tests in three periods: pre-BOS, from BOS diagnosis to 6 months, and 6-18 months after diagnosis. The effect of treatment on FEV1 trajectory was analyzed by univariate and multivariate linear regression. The Kaplan-Meier method was used to estimate survival.The FEV1 percent predicted value at diagnosis was 46% (interquartile range, 35-57%) for trial participants and 53% (interquartile range, 41-64%) for the retrospective cohort. There was a concomitant mild reduction in FVC, as well as a marked reduction in forced expiratory flow, midexpiratory phase, at diagnosis. While there was individual heterogeneity, the overall FEV1 trajectory was characterized by a marked decline within 6 months prior to BOS diagnosis, followed by stability of FEV1 early after diagnosis and a slow rate of decline beyond 6 months. The effect of the trial medications on FEV1 trajectory after BOS diagnosis was a mean rate of change of 0.92% predicted per month (95% confidence interval, -0.53 to 2.37) compared with the retrospective cohort, but this was not statistically significant. Two-year overall survival rates were 76% and 72% for the study participants and the retrospective cohort patients, respectively. Earlier time to diagnosis after hematopoietic cell transplant and severity of FVC at diagnosis were significantly associated with reduced survival.The FEV1 trajectory in patients with BOS after hematopoietic cell transplant in a contemporary era of management follows a predominant pattern of rapid FEV1 decline in the 6 months prior to diagnosis, followed by FEV1 stabilization after diagnosis.

    View details for PubMedID 27513368

    View details for PubMedCentralID PMC5122479

  • Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Williams, K. M., Cheng, G., Pusic, I., Jagasia, M., Burns, L., Ho, V. T., Pidala, J., Palmer, J., Johnston, L., Mayer, S., Chien, J. W., Jacobsohn, D. A., Pavletic, S. Z., Martin, P. J., Storer, B. E., Inamoto, Y., Chai, X., Flowers, M. E., Lee, S. J. 2016; 22 (4): 710-716

    Abstract

    Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.

    View details for DOI 10.1016/j.bbmt.2015.10.009

    View details for Web of Science ID 000373093500017

    View details for PubMedCentralID PMC4801753

  • Central Nervous System Involvement of Chronic Graft Versus Host Disease Neppalli, A., Johnston, L. ELSEVIER SCIENCE INC. 2016: S407
  • Prednisone (PDN)/Sirolimus (SRL) Compared to PDN/SRL/Calcineurin Inhibitor (CNI) as Treatment for Chronic Graft-Versus-Host-Disease (cGVHD): A Randomized Phase II Study from the Blood and Marrow Transplant Clinical Trials Network Carpenter, P. A., Logan, B. R., Lee, S. J., Weisdorf, D. J., Johnston, L., Costa, L. J., Kitko, C. L., Bolanos-Meade, J., Alousi, A. M., Horowitz, M. M., Abhyankar, S., Waller, E. K., Mendizabal, A., Wang, Y., Lazaryan, A., Carter, S. L., Nemecek, E. R., Pavletic, S. Z., Cutler, C. S., Arora, M., BMT CTN ELSEVIER SCIENCE INC. 2016: S50?S52
  • Long-Term Outcomes of AML Patients Using Total Lymphoid Irradiation with Anti-Thymocyte Globulin Nakasone, H., Miklos, D. B., Meyer, E., Rezvani, A., Muffly, L., Weng, W., Arai, S., Johnston, L., Laport, G. G., Shizuru, J. A., Negrin, R., Strober, S., Lowsky, R. ELSEVIER SCIENCE INC. 2016: S204?S205
  • Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Williams, K. M., Cheng, G. S., Pusic, I., Jagasia, M., Burns, L., Ho, V. T., Pidala, J., Palmer, J., Johnston, L., Mayer, S., Chien, J. W., Jacobsohn, D. A., Pavletic, S. Z., Martin, P. J., Storer, B. E., Inamoto, Y., Chai, X., Flowers, M. E., Lee, S. J. 2016; 22 (4): 710?16

    Abstract

    Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.

    View details for PubMedID 26475726

  • Donor-Derived CIK Cell Infusion As Consolidative Therapy after Non-Myeloablative Allogeneic Transplant in Patients with Myeloid Neoplasms Narayan, R., Benjamin, J., Laport, G., Tian, L., Tate, K., Elder, L., Galvez, L., Armstrong, R., Sheehan, K., Lowsky, R., Arai, S., Johnston, L., Miklos, D., Muffly, L. S., Rezvani, A. R., Shizuru, J., Weng, W., Strober, S., Negrin, R., Meyer, E. AMER SOC HEMATOLOGY. 2015
  • Intensive Care Utilization for Hematopoietic Cell Transplant Recipients BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Jenkins, P., Johnston, L. J., Pickham, D., Chang, B., Rizk, N., Tierney, D. K. 2015; 21 (11): 2023-2027

    Abstract

    Blood and marrow transplantation (BMT) is a potentially curative therapy for a number of malignant and nonmalignant diseases. Multiple variables, including age, comorbid conditions, disease, disease stage, prior therapies, degree of donor-recipient matching, type of transplantation, and dose intensity of the preparative regimen, affect both morbidity and mortality. Despite tremendous gains in supportive care, BMT remains a high-risk medical therapy. A critically ill BMT recipient may require transfer to an intensive care unit (ICU) and the specialized medical and nursing care that can be provided, such as mechanical ventilation and vasopressor support. Mortality for BMT recipients requiring care in an ICU is high. This paper will describe the experience of the Stanford Blood and Marrow Transplant Program in developing and implementing guidelines to maximize the benefit of intensive care for critically ill BMT recipients.

    View details for DOI 10.1016/j.bbmt.2015.07.026

    View details for Web of Science ID 000363357200024

    View details for PubMedID 26238809

  • Sexuality, Menopausal Symptoms, and Quality of Life in Premenopausal Women in the First Year Following Hematopoietic Cell Transplantation ONCOLOGY NURSING FORUM Tierney, D. K., Palesh, O., Johnston, L. 2015; 42 (5): 488-497

    Abstract

    To describe sexuality, menopausal symptoms, and quality of life (QOL) in premenopausal women in the first year following hematopoietic cell transplantation (HCT). .One-year prospective longitudinal study..Stanford University Medical Center in California..63 premenopausal female recipients of HCT with a mean age of 34.5 years..Three instruments were used.Sexuality, menopausal symptoms, and QOL..At one year post-HCT, women reported absent to low desire and arousal, adequate lubrication less than half of the time, absent or rare orgasm, pain during vaginal penetration more than half the time, and dissatisfaction with overall sex life. Women also reported moderate to severe vasomotor symptoms, including hot flashes, night sweats, and sweating. Twenty-one women were avoiding sexual activity, and 25 women were not sexually active. Mean QOL scores significantly increased (p = 0.028) in the first year, signifying an improvement in QOL. Variables predictive of improved QOL at one year post-HCT include decreased psychosocial and physical symptoms, sexual satisfaction, and pre-HCT QOL score..One year post-HCT, women reported sexual dysfunction, sexual dissatisfaction, and menopausal symptoms, which negatively affect QOL. .Nurses and other healthcare providers working with recipients of HCT can provide anticipatory guidance on potential changes in sexuality and menopausal symptoms to facilitate adaptation by reducing discordance between expectations and new realities. .

    View details for DOI 10.1188/15.ONF.488-497

    View details for Web of Science ID 000363892900010

    View details for PubMedID 26302277

  • National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. The 2014 Ancillary Therapy and Supportive Care Working Group Report BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Carpenter, P. A., Kitko, C. L., Elad, S., Flowers, M. E., Gea-Banacloche, J. C., Halter, J. P., Hoodin, F., Johnston, L., Lawitschka, A., McDonald, G. B., Opipari, A. W., Savani, B. N., Schultz, K. R., Smith, S. R., Syrjala, K. L., Treister, N., Vogelsang, G. B., Williams, K. M., Pavletic, S. Z., Martin, P. J., Lee, S. J., Couriel, D. R. 2015; 21 (7): 1167-1187

    Abstract

    The 2006 National Institutes of Health (NIH) Consensus paper presented recommendations by the Ancillary Therapy and Supportive Care Working Group to support clinical research trials in chronic graft-versus-host disease (GVHD). Topics covered in that inaugural effort included the prevention and management of infections and common complications of chronic GVHD, as well as recommendations for patient education and appropriate follow-up. Given the new literature that has emerged during the past 8 years, we made further organ-specific refinements to these guidelines. Minimum frequencies are suggested for monitoring key parameters relevant to chronic GVHD during systemic immunosuppressive therapy and, thereafter, referral to existing late effects consensus guidelines is advised. Using the framework of the prior consensus, the 2014 NIH recommendations are organized by organ or other relevant systems and graded according to the strength and quality of supporting evidence.

    View details for DOI 10.1016/j.bbmt.2015.03.024

    View details for PubMedID 25838185

  • A Multicenter Phase I/II Study of Relapse Prophylaxis with Nilotinib after Hematopoietic Cell Transplantation (HCT) for High-Risk Philadelphia Chromosome-Positive (Ph plus ) Leukemias Carpenter, P. A., Johnston, L., Fernandez, H., Radich, J., Mauro, M. J., Flowers, M. D., Martin, P. J., Gooley, T. ELSEVIER SCIENCE INC. 2015: S274?S276
  • Encouraging Results of a Phase II Trial of Inhaled Fluticasone Propionate, Azithromycin, and Montelukast (FAM) May Maintain Lung Function in Bronchiolitis Obliterans Syndrome (BOS) after Hematopoietic Cell Transplantation Williams, K. M., Cheng, G., Pusic, I., Jagasia, M. H., Burns, L. J., Ho, V. T., Pidala, J., Palmer, J., Johnston, L., Mayer, S., Jacobsohn, D. A., Martin, P. J., Storer, B. E., Inamoto, Y., Chai, X., Flowers, M. D., Lee, S. J. ELSEVIER SCIENCE INC. 2015: S61?S62
  • BOS after HCT: Preceding Events, Diagnostic Characteristics, and Natural History of Patients Treated on a Prospective Trial Cheng, G., Pusic, I., Jagasia, M. H., Burns, L. J., Ho, V. T., Pidala, J., Palmer, J., Johnston, L., Mayer, S., Chai, X., Lee, S. J., Williams, K. M. ELSEVIER SCIENCE INC. 2015: S172?S173
  • Allogeneic hematopoietic cell transplant for normal karyotype AML: indirect evidence of selection for adverse molecular profile. Bone marrow transplantation Percival, M. M., Medeiros, B. C., Tian, L., Robeson, S., Laport, G. G., Johnston, L. J., Shizuru, J. A., Miklos, D. B., Arai, S., Weng, W. K., Negrin, R. S., Lowsky, R. 2015

    View details for PubMedID 25893457

  • Non-Myeloablative Allogeneic Transplantation Resulting in Clinical and Molecular Remission with Low Non-Relapse Mortality (NRM) in Patients with Advanced Stage Mycosis Fungoides (MF) and Sezary Syndrome (SS) Weng, W., Armstrong, R., Arai, S., Johnston, L., Laport, G. G., Lowsky, R., Miklos, D. B., Shizuru, J. A., Benjamin, J. E., Negrin, R. S., Reddy, S., Million, L., Hoppe, R. T., Kim, Y. H. AMER SOC HEMATOLOGY. 2014
  • Sleep Disruption in Hematopoietic Cell Transplantation Recipients: Prevalence, Severity, and Clinical Management BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Jim, H. S., Evans, B., Jeong, J. M., Gonzalez, B. D., Johnston, L., Nelson, A. M., Kesler, S., Phillips, K. M., Barata, A., Pidala, J., Palesh, O. 2014; 20 (10): 1465-1484

    Abstract

    Sleep disruption is common among hematopoietic cell transplant (HCT) recipients, with over 50% of recipients experiencing sleep disruption pre-transplant, with up to 82% of patients experiencing moderate to severe sleep disruption during hospitalization for transplant and up to 43% after transplant. These rates of sleep disruption are substantially higher than what we see in the general population. Although sleep disruption can be distressing to patients and contribute to diminished quality of life, it is rarely discussed during clinical visits. The goal of the current review is to draw attention to sleep disruption and disorders (ie, insomnia, obstructive sleep apnea, restless legs syndrome) as a clinical problem in HCT in order to facilitate patient education, intervention, and research. We identified 35 observational studies published in the past decade that examined sleep disruption or disorders in HCT. Most studies utilized a single item measure of sleep, had small sample size, and included heterogeneous samples of patients. Six studies of the effects of psychosocial and exercise interventions on sleep in HCT have reported no significant improvements. These results highlight the need for rigorous observational and interventional studies of sleep disruption and disorders in HCT recipients..

    View details for DOI 10.1016/j.bbmt.2014.04.010

    View details for Web of Science ID 000342117100003

    View details for PubMedCentralID PMC4163090

  • Sleep disruption in hematopoietic cell transplantation recipients: prevalence, severity, and clinical management. Biology of blood and marrow transplantation Jim, H. S., Evans, B., Jeong, J. M., Gonzalez, B. D., Johnston, L., Nelson, A. M., Kesler, S., Phillips, K. M., Barata, A., Pidala, J., Palesh, O. 2014; 20 (10): 1465-1484

    Abstract

    Sleep disruption is common among hematopoietic cell transplant (HCT) recipients, with over 50% of recipients experiencing sleep disruption pre-transplant, with up to 82% of patients experiencing moderate to severe sleep disruption during hospitalization for transplant and up to 43% after transplant. These rates of sleep disruption are substantially higher than what we see in the general population. Although sleep disruption can be distressing to patients and contribute to diminished quality of life, it is rarely discussed during clinical visits. The goal of the current review is to draw attention to sleep disruption and disorders (ie, insomnia, obstructive sleep apnea, restless legs syndrome) as a clinical problem in HCT in order to facilitate patient education, intervention, and research. We identified 35 observational studies published in the past decade that examined sleep disruption or disorders in HCT. Most studies utilized a single item measure of sleep, had small sample size, and included heterogeneous samples of patients. Six studies of the effects of psychosocial and exercise interventions on sleep in HCT have reported no significant improvements. These results highlight the need for rigorous observational and interventional studies of sleep disruption and disorders in HCT recipients..

    View details for DOI 10.1016/j.bbmt.2014.04.010

    View details for PubMedID 24747335

  • Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT BLOOD Cutler, C., Logan, B., Nakamura, R., Johnston, L., Choi, S., Porter, D., Hogan, W. J., Pasquini, M., MacMillan, M. L., Hsu, J. W., Waller, E. K., Grupp, S., McCarthy, P., Wu, J., Hu, Z., Carter, S. L., Horowitz, M. M., Antin, J. H. 2014; 124 (8): 1372-1377

    Abstract

    Grades 2-4 acute graft-versus-host disease (GVHD) occurs in approximately 35% of matched, related donor (MRD) allogeneic hematopoietic cell transplantation (HCT) recipients. We sought to determine if the combination of tacrolimus and sirolimus (Tac/Sir) was more effective than tacrolimus and methotrexate (Tac/Mtx) in preventing acute GVHD and early mortality after allogeneic MRD HCT in a phase 3, multicenter trial. The primary end point of the trial was to compare 114-day grades 2-4 acute GVHD-free survival using an intention-to-treat analysis of 304 randomized subjects. There was no difference in the probability of day 114 grades 2-4 acute GVHD-free survival (67% vs 62%, P = .38). Grades 2-4 GVHD was similar in the Tac/Sir and Tac/Mtx arms (26% vs 34%, P = .48). Neutrophil and platelet engraftment were more rapid in the Tac/Sir arm (14 vs 16 days, P < .001; 16 vs 19 days, P = .03). Oropharyngeal mucositis was less severe in the Tac/Sir arm (peak Oral Mucositis Assessment Scale score 0.70 vs 0.96, P < .001), but otherwise toxicity was similar. Chronic GVHD, relapse-free survival, and overall survival at 2 years were no different between study arms (53% vs 45%, P = .06; 53% vs 54%, P = .77; and 59% vs 63%, P = .36). Based on similar long-term outcomes, more rapid engraftment, and less oropharyngeal mucositis, the combination of Tac/Sir is an acceptable alternative to Tac/Mtx after MRD HCT. This study was funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; and the trial was registered at www.clinicaltrials.gov as #NCT00406393.

    View details for DOI 10.1182/blood-2014-04-567164

    View details for Web of Science ID 000342761900031

    View details for PubMedID 24982504

    View details for PubMedCentralID PMC4141519

  • Total lymphoid irradiation-antithymocyte globulin conditioning and allogeneic transplantation for patients with myelodysplastic syndromes and myeloproliferative neoplasms. Biology of blood and marrow transplantation Benjamin, J., Chhabra, S., Kohrt, H. E., Lavori, P., Laport, G. G., Arai, S., Johnston, L., Miklos, D. B., Shizuru, J. A., Weng, W., Negrin, R. S., Lowsky, R. 2014; 20 (6): 837-843

    Abstract

    Allogeneic hematopoietic cell transplantation (allo HCT) is the only curative therapy for the myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), but treatment toxicity has been a barrier to its more widespread use. The nonmyeloablative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) permits the establishment of donor hematopoiesis necessary for the graft-versus-malignancy effect and is protective against acute graft-versus-host disease (aGVHD), but it has minimal direct cytotoxicity against myeloid diseases. We explored the use of TLI-ATG conditioning to treat 61 patients with allo HCT for MDS (n = 32), therapy-related myeloid neoplasms (n = 15), MPN (n = 9), and chronic myelomonocytic leukemia (n = 5). The median age of all patients was 63 years (range, 50 to 73). The cumulative incidence of aGVHD grades II to IV was 14% (95% confidence interval [CI], 4% to 23%) and for grades III to IV, 4% (95% CI, 0 to 9%), and it did not differ between patients who received allografts from related or unrelated donors. The cumulative incidence of nonrelapse mortality (NRM) at 100 days, 12 months, and 36 months was 0%, 7%, and 11%. Overall survival and progression-free survival were 41% (95% CI, 29% to 53%) and 35% (95% CI, 23% to 48%), respectively. The safety and tolerability of TLI-ATG, as exemplified by its low NRM, provides a foundation for further risk-adapted or prophylactic interventions to prevent disease progression.

    View details for DOI 10.1016/j.bbmt.2014.02.023

    View details for PubMedID 24607552

  • Outcome of Tandem Autologous/Allogeneic Hematopoietic Cell Transplantation in High-Risk Non Hodgkin's Lymphoma Patients: Stanford University Experience Wudhikarn, K., Lavori, P., Arai, S., Johnston, L., Laport, G. G., Lowsky, R., Miklos, D. B., Shizuru, J. A., Hoppe, R. T., Benjamin, J., Meyer, E., Negrin, R., Weng, W. ELSEVIER SCIENCE INC. 2014: S164
  • Ocular Gvhd: Epidemiology, Risk Factors and Impact on Quality of Life-a Chronic Gvhd Consortium Study Jagasia, M. H., Chai, X., Pidala, J., Inamoto, Y., Arora, M., Cutler, C. S., Flowers, M. D., Johnston, L., Pavletic, S. Z., Lee, S. J. ELSEVIER SCIENCE INC. 2014: S269
  • Outcomes After Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation with Total Lymphoid Irradiation and Anti-Thymocyte Globulin in Lymphoid Malignancies After Failed Autologous Transplantation BMT Tandem Meetings Kanate, A. S., Efron, B., Chhabra, S., Kohrt, H., Shizuru, J. A., Laport, G. G., Miklos, D. B., Benjamin, J., Johnston, L., Arai, S., Weng, W., Negrin, R., Strober, S., Lowsky, R. ELSEVIER SCIENCE INC. 2013: S154?S155
  • TLI-ATG Conditioning and Allogeneic Transplantation for Patients with MDS and MPN BMT Tandem Meetings Benjamin, J., Chhabra, S., Kohrt, H., Laport, G. G., Arai, S., Johnston, L., Miklos, D. B., Shizuru, J. A., Weng, W., Negrin, R., Lowsky, R. ELSEVIER SCIENCE INC. 2013: S113?S114
  • Non-Myeloablative Conditioning with Total Lymphoid Irradiation and ATG and Allogeneic Transplantation for Patients with Myelodysplastic Syndrome, Therapy-Related Myeloid Neoplasms, and Myeloproliferative Neoplasms. 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Benjamin, J., Chhabra, S., Kohrt, H. E., Laport, G. G., Arai, S., Johnston, L., Miklos, D. B., Shizuru, J. A., Weng, W., Negrin, R. S., Lowsky, R. AMER SOC HEMATOLOGY. 2012
  • Impact of Day 28 Absolute Lymphocyte Count On Outcome of Hematopoietic Cell Transplant (HCT) in CR1 for Adult Patients with Acute Lymphoblastic Leukemia 54th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Rose, J. A., Dunn, T. J., Liedtke, M., Elson, P., Kalaycio, M., Copelan, E., Sobecks, R., Sekeres, M. A., Hobson, S., Johnston, L., Tench, S., Cross, S., Advani, A. AMER SOC HEMATOLOGY. 2012
  • Long-term outcomes after high dose therapy and autologous haematopoietic cell rescue for refractory/relapsed Hodgkin lymphoma BRITISH JOURNAL OF HAEMATOLOGY Minn, A. Y., Riedel, E., Halpern, J., Johnston, L. J., Horning, S. J., Hoppe, R. T., Goodman, K. A. 2012; 159 (3): 329-339

    Abstract

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

    View details for DOI 10.1111/bjh.12038

    View details for Web of Science ID 000309717500009

    View details for PubMedID 22966754

  • Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors NEW ENGLAND JOURNAL OF MEDICINE Anasetti, C., Logan, B. R., Lee, S. J., Waller, E. K., Weisdorf, D. J., Wingard, J. R., Cutler, C. S., Westervelt, P., Woolfrey, A., Couban, S., Ehninger, G., Johnston, L., Maziarz, R. T., Pulsipher, M. A., Porter, D. L., Mineishi, S., McCarty, J. M., Khan, S. P., Anderlini, P., Bensinger, W. I., Leitman, S. F., Rowley, S. D., Bredeson, C., Carter, S. L., Horowitz, M. M., Confer, D. L. 2012; 367 (16): 1487-1496

    Abstract

    Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia.We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37).The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse.We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.).

    View details for DOI 10.1056/NEJMoa1203517

    View details for Web of Science ID 000309904500006

    View details for PubMedID 23075175

  • Yield of Single versus Upper and Lower Endoscopic Biopsies in the Diagnosis of Gastrointestinal Graft-Versus-Host Disease in Patients with Prior Allogeneic Hematopoietic Stem Cell Transplantation Liu, A., Meyer, E., Johnston, L., Gerson, L. NATURE PUBLISHING GROUP. 2012: S731
  • Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence BLOOD Arai, S., Sahaf, B., Narasimhan, B., Chen, G. L., Jones, C. D., Lowsky, R., Shizuru, J. A., Johnston, L. J., Laport, G. G., Weng, W., Benjamin, J. E., Schaenman, J., Brown, J., Ramirez, J., Zehnder, J. L., Negrin, R. S., Miklos, D. B. 2012; 119 (25): 6145-6154

    Abstract

    B cells are involved in the pathogenesis of chronic GVHD (cGVHD). We hypothesized that prophylactic anti-B-cell therapy delivered 2 months after transplantation would decrease allogeneic donor B-cell immunity and possibly the incidence of cGVHD. Therefore, in the present study, patients with high-risk chronic lymphocytic leukemia (n = 22) and mantle-cell lymphoma (n = 13) received a total lymphoid irradiation of 80 cGy for 10 days and antithymocyte globulin 1.5 mg/kg/d for 5 days. Rituximab (375 mg/m(2)) was infused weekly on days 56, 63, 70, and 77 after transplantation. The incidence of acute GVHD was 6%. The cumulative incidence of cGVHD was 20%. Nonrelapse mortality was 3%. Rituximab treatment after allogeneic transplantation significantly reduced B-cell allogeneic immunity, with complete prevention of alloreactive H-Y Ab development in male patients with female donors (P = .01). Overall survival and freedom from progression at 4 years for chronic lymphocytic leukemia patients were 73% and 47%, respectively; for mantle-cell lymphoma patients, they were 69% and 53%, respectively.

    View details for DOI 10.1182/blood-2011-12-395970

    View details for PubMedID 22563089

  • Sirolimus and mycophenolate mofetil as GVHD prophylaxis in myeloablative, matched-related donor hematopoietic cell transplantation BONE MARROW TRANSPLANTATION Johnston, L., Florek, M., Armstrong, R., McCune, J. S., Arai, S., Brown, J., Laport, G., Lowsky, R., Miklos, D., Shizuru, J., Sheehan, K., Lavori, P., Negrin, R. 2012; 47 (4): 581-588

    Abstract

    We investigated sirolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis in patients with advanced hematological malignancies receiving myeloablative hematopoietic cell transplantation (HCT) from HLA-identical sibling donors. On the basis of pre-study stopping rules, the trial was closed to accrual after enrollment of 11 adult patients. In all, 7 of the 11 patients received BU-containing preparative regimens. Sirolimus was discontinued in three patients because of the toxicity-related events of severe sinusoidal obstructive syndrome, portal vein thrombosis, altered mental status and in one patient because of the risk of poor wound healing. In all, 6 of the 11 patients developed grade II-IV acute GVHD (AGVHD) a median of 15.5 days post HCT. Two of three patients with grade IV AGVHD had sirolimus discontinued by 9 days post HCT. All patients responded to AGVHD therapy without GVHD-related deaths. There were two non-relapse- and two relapse-related deaths. At a median follow-up of 38 months (2-47 months), 7 of 11 patients were alive without disease. MMF and sirolimus GVHD prophylaxis did not reduce the risk of AGVHD, however, there were no GVHD-related deaths. The severe toxicities in the patients receiving the BU-containing preparative regimens limited the continued use of sirolimus and MMF for the prevention of AGVHD.

    View details for DOI 10.1038/bmt.2011.104

    View details for Web of Science ID 000302576700018

    View details for PubMedID 21552302

    View details for PubMedCentralID PMC3163055

  • Long-Term Outcome of Patients with Metastatic Breast Cancer Treated with High-Dose Chemotherapy and Transplantation of Purified Autologous Hematopoietic Stem Cells BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Mueller, A. M., Kohrt, H. E., Cha, S., Laport, G., Klein, J., Guardino, A. E., Johnston, L. J., Stockerl-Goldstein, K. E., Hanania, E., Juttner, C., Blume, K. G., Negrin, R. S., Weissman, I. L., Shizuru, J. A. 2012; 18 (1): 125-133

    Abstract

    Metastatic breast cancer remains a major treatment challenge. The use of high-dose chemotherapy (HDCT) with rescue by autologous mobilized peripheral blood (MPB) is controversial, in part because of contamination of MPB by circulating tumor cells. CD34(+)Thy-1(+) selected hematopoietic stem cells (HSC) represent a graft source with a greater than 250,000-fold reduction in cancer cells. Here, we present the long-term outcome of a pilot study to determine feasibility and engraftment using HDCT and purified HSC in patients with metastatic breast cancer. Twenty-two patients who had been treated with standard chemotherapy were enrolled into a phase I/II trial between December 1996 and February 1998, and underwent HDCT followed by rescue with CD34(+)Thy-1(+) HSC isolated from autologous MPB. More than 12 years after the end of the study, 23% (5 of 22) of HSC recipients are alive, and 18% (4 of 22) are free of recurrence with normal hematopoietic function. Median progression-free survival (PFS) was 16 months, and median overall survival (OS) was 60 months. Retrospective comparison with 74 patients transplanted between February 1995 and June 1999 with the identical HDCT regimen but rescue with unmanipulated MPB indicated that 9% of patients are alive, and 7% are without disease. Median PFS was 10 months, and median OS was 28 months. In conclusion, cancer-depleted HSC following HDCT resulted in better than expected 12- to 14-year PFS and OS in a cohort of metastatic breast cancer patients. These data prompt us to look once again at purified HSC transplantation in a protocol powered to test for efficacy in advanced-stage breast cancer patients.

    View details for DOI 10.1016/j.bbmt.2011.07.009

    View details for PubMedID 21767515

  • Increased Incidence of Chronic Graft-Versus-Host Disease (GVHD) and No Survival Advantage with Filgrastim-Mobilized Peripheral Blood Stem Cells (PBSC) Compared to Bone Marrow (BM) Transplants From Unrelated Donors: Results of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 0201, a Phase III, Prospective, Randomized Trial 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Anasetti, C., Logan, B. R., Lee, S. J., Waller, E. K., Weisdorf, D. J., Wingard, J. R., Cutler, C. S., Westervelt, P., Woolfrey, A., Couban, S., Johnston, L., Maziarz, R. T., Pulsipher, M., Anderlini, P., Bensinger, W. I., Leitman, S. F., Rowley, S. D., Carter, S. L., Horowitz, M. M., Confer, D. L. AMER SOC HEMATOLOGY. 2011: 3?3
  • A Phase 1 Open Label, Dose Escalation Study of Nilotinib in Steroid Dependent/Refractory Chronic Graft-Versus-Host Disease 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Chen, G. L., Carpenter, P. A., Broady, R., Gregory, T. B., Arai, S., Johnston, L., Flowers, M. E., Beumer, J. H., Mendolsohn, J., Zhou, X., Perloff, S. H., Otani, J. M., Miklos, D. B. AMER SOC HEMATOLOGY. 2011: 866?67
  • Adoptive Immunotherapy with Cytokine-Induced Killer Cells for Patients with Relapsed Hematologic Malignancies after Allogeneic Hematopoietic Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Laport, G. G., Sheehan, K., Baker, J., Armstrong, R., Wong, R. M., Lowsky, R., Johnston, L. J., Shizuru, J. A., Miklos, D., Arai, S., Benjamin, J. E., Weng, W., Negrin, R. S. 2011; 17 (11): 1679-1687

    Abstract

    Donor leukocyte infusions induce remissions in some patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplantation (HCT); however, graft-versus-host disease (GVHD) remains the major complication of this strategy. Cytokine-induced killer (CIK) cells are a unique population of cytotoxic T lymphocytes that express the CD3(+)CD56(+) phenotype and show marked up-regulation of the natural killer cell receptor NKG2D (CD314). CIK cells are non-major histocompatibility complex-restricted and NKG2D-dependent in target recognition and cytotoxicity. We explored the feasibility of ex vivo expansion of allogeneic CIK cells in patients with relapsed hematologic malignancies after allogeneic HCT. Eighteen patients (median age, 53 years; range, 20-69 years) received CIK cell infusions at escalating doses of 1 × 10(7) CD3(+) cells/kg (n = 4), 5 × 10(7) CD3(+) cells/kg (n = 6), and 1 × 10(8) CD3(+) cells/kg (n = 8). The median expansion of CD3(+) cells was 12-fold (range, 4- to 91-fold). CD3(+)CD56(+) cells represented a median of 11% (range, 4%-44%) of the harvested cells, with a median 31-fold (range, 7- to 515-fold) expansion. Median CD3(+)CD314(+) cell expression was 53% (range, 32%-78%) of harvested cells. Significant cytotoxicity was demonstrated in vitro against a panel of human tumor cell lines. Acute GVHD grade I-II was seen in 2 patients, and 1 patient had limited chronic GVHD. After a median follow-up of 20 months (range, 1-69 months) from CIK infusion, the median overall survival was 28 months, and the median event-free survival was 4 months. All deaths were due to relapsed disease; however, 5 patients had longer remissions after infusion of CIK cells than from allogeneic HCT to relapse. Our findings indicate that this form of adoptive immunotherapy is well tolerated and induces a low incidence of GVHD, supporting further investigation as an upfront modality to enhance graft-versus-tumor responses in high-risk patient populations.

    View details for DOI 10.1016/j.bbmt.2011.05.012

    View details for PubMedID 21664472

  • A phase 1 study of imatinib for corticosteroid-dependent/refractory chronic graft-versus-host disease: response does not correlate with anti-PDGFRA antibodies BLOOD Chen, G. L., Arai, S., Flowers, M. E., Otani, J. M., Qiu, J., Cheng, E. C., McMillan, A., Johnston, L. J., Shizuru, J. A., Miklos, D. B. 2011; 118 (15): 4070-4078

    Abstract

    Stimulatory antiplatelet derived growth factor receptor ? (PDGFRA) antibodies have been associated with extensive chronic graft-versus-host disease (cGVHD). We performed a phase 1 dose escalation trial of imatinib in corticosteroid-dependent/refractory cGVHD to assess the safety of imatinib and test the hypothesis that abrogation of PDGFRA signaling can ameliorate the manifestations of cGVHD. Fifteen patients were enrolled. Mean follow-up time was 56.6 weeks (range, 18-82.4 weeks). Imatinib 400 mg daily was associated with more frequent moderate to life-threatening adverse events than 200 mg daily. The main adverse events were nausea, edema, confusion, diarrhea, liver function test elevation, fatigue, and myalgia. The overall response rate was 40% (6 of 15). The treatment failure rate was 40% (6 of 15). Twenty percent (3 of 15) of subjects had stable disease. Of 4 subjects with phospho-PDGFRA and phospho-PDGFRB immunohistochemistry studies before and after treatment, inhibition of phosphorylation was observed in 3 but correlated with response in one. Anti-PDGFRA antibodies were observed in 7 of 11 evaluable subjects but correlated with clinical activity in 4. We conclude that cGVHD responds to imatinib through multiple pathways that may include PDGFRA signal transduction. This study is registered at www.clinicaltrials.gov as #NCT00760981.

    View details for DOI 10.1182/blood-2011-03-341693

    View details for Web of Science ID 000296282200013

    View details for PubMedID 21828142

  • Rationale and Design of the Chronic GVHD Cohort Study: Improving Outcomes Assessment in Chronic GVHD BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Lee, S. J., Flowers, M. E., Martin, P. J., Carpenter, P., Hansen, J., Chai, X., Kurland, B., Storer, B., Arai, S., Johnston, L., Miklos, D., Weisdorf, D., Arora, M., Majhail, N., Cutler, C., Jagasia, M., Palmer, J., Pidala, J., Westervelt, P., Pusic, I., Giralt, S., Goldberg, J., Couriel, D., Kitko, C., Pavletic, S. Z., Vogelsang, G. B., Gilman, A., Schultz, K. 2011; 17 (8): 1114-1120

    Abstract

    In 2005, the National Institutes of Health sponsored a Consensus Development Project on Criteria for Clinical Trials in chronic graft-versus-host (cGVHD) to achieve consensus about key elements of cGVHD research, including definitions for diagnosis, severity scoring, and response measures. To test these proposed definitions, a multicenter prospective cohort study of people with cGVHD is ongoing. This study will evaluate the performance of proposed prognostic factors, measures of disease activity, and surrogate endpoints for therapeutic response. Data are collected at 6-month intervals in a heterogeneous population of patients reflecting modern transplant techniques and posttransplantation clinical management (target enrollment 672 with cGVHD from 10 transplantation centers). This report describes the rationale, design, and methods of the cGVHD cohort study, and invites other investigators to collaborate with the Consortium to analyze data or specimens.

    View details for DOI 10.1016/j.bbmt.2011.05.007

    View details for Web of Science ID 000293429600003

    View details for PubMedID 21664473

  • Early CMV Viremia Is Associated with Impaired Viral Control following Nonmyeloablative Hematopoietic Cell Transplantation with a Total Lymphoid Irradiation and Antithymocyte Globulin Preparative Regimen BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Schaenman, J. M., Shashidhar, S., Rhee, C., Wong, J., Navato, S., Wong, R. M., Ho, D. Y., Arai, S., Johnston, L., Brown, J. M. 2011; 17 (5): 693-702

    Abstract

    The reconstitution of immune function after hematopoietic cell transplant (HCT) plays an important role in the control of viral infections. Both donor and recipient cytomegalovirus (CMV) serostatus has been shown to contribute to effective immune function; however, the influence of a nonmyeloablative preparative (NMA) regimen using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) on antiviral immune reconstitution has not yet been described. In 117 recipients of NMA HCT patients following ATG and TLI, not unexpectedly, CMV viremia was seen in approximately 60% of the seropositive patients regardless of donor serostatus, and recipient seropositivity significantly increased the odds of CMV viremia after transplant in a multivariate analysis. The administration of ATG and TLI resulted in a strikingly earlier viremia in the posttransplant period when compared to the previously reported timing of viremia following myeloablative preparative regimens, especially for transplant recipients who were seropositive for CMV with seronegative donors. Furthermore, early viremia in the setting of a CMV naïve donor was associated with a delay in functional antiviral control. These observations demonstrate the dynamic nature of immunity in relation to CMV antigen exposure in the complex environment resulting from NMA conditions where both donor and residual recipient immune response affect viral control.

    View details for DOI 10.1016/j.bbmt.2010.08.010

    View details for Web of Science ID 000290061500012

    View details for PubMedID 20736077

  • Long-term Clinical Course of Dry Eye in Patients With Chronic Graft-Versus-Host Disease Referred for Eye Examination CORNEA Sales, C. S., Johnston, L. J., Ta, C. N. 2011; 30 (2): 143-149

    Abstract

    To assess the long-term clinical course of dry eye in patients with chronic graft-versus-host disease (cGVHD).A prospective case series of 49 patients with cGVHD was conducted. Complete history and ophthalmic examination were performed at baseline and at 36 months (range, 26-53). All patients received treatment for dry eye.Of the 49 participants, 18 (37%) had expired at the time of the 3-year eye examination, 11 were lost to follow-up, 11 declined or were unable to attend the final examination, and 9 (18%) completed the study. There was a statistically insignificant improvement in symptoms of dry eye assessed by the ocular surface disease index [start vs. endpoint: 36 ± 22 (range, 4-72) vs. 30 ± 27 (range, 4-86); P = 0.51]. Visual acuity remained stable at approximately 20/20. Lissamine green staining improved and Schirmer test (with anesthetic) worsened, but neither trend was statistically or clinically significant.Stable visual acuity, tear production, and lissamine green staining and a statistically insignificant improvement in dry eye symptoms were observed in the 9 participants who completed this 3-year prospective case series of 49 patients with cGVHD. Insofar as these patients represent a minority (18%) of the original cohort, their clinical course may not be generalizable to all patients with cGVHD but may still suggest that this patient population's prognosis could be characterized by stability and excellent vision. Sufficiently powered prospective studies are required to validate these postulates.

    View details for DOI 10.1097/ICO.0b013e3181e9b3bf

    View details for PubMedID 20885310

  • Long-term outcomes in patients with high-risk myeloid malignancies following matched related donor hematopoietic cell transplantation with myeloablative conditioning of BU, etoposide and CY BONE MARROW TRANSPLANTATION Naik, S., Wong, R., Arai, S., Brown, J., Laport, G., Lowsky, R., Miklos, D., Shizuru, J., Blume, K., Negrin, R., Johnston, L. 2011; 46 (2): 192-199

    Abstract

    Patients with high-risk or advanced myeloid malignancies have limited effective treatment options. These include high-dose therapy followed by allogeneic hematopoietic cell transplantation (HCT). We report a single-institution, long-term follow-up of 96 patients, median age 50 (range, 20-60) years, who received HLA-matched related HCT between 1992 and 2007. All patients were treated with a uniform preparatory regimen intended to enhance the widely used regimen of BU and CY that included: BU 16.0?mg/kg (days -8 to -5), etoposide 60?mg/kg (day -4), CY 60?mg/kg (day -2) with GVHD prophylaxis of CsA or FK506 and prednisone. Disease status at transplantation was high-risk AML (n=41), CML in second chronic phase or blast crisis (n=8), myelofibrosis and myeloproliferative disorders (n=8), and myelodysplasia (n=39). Thirty-six percent (n=35) of patients received BM whereas 64% (n=61) received G-CSF-mobilized PBPC. With a median follow-up of 5.6 years (range, 1.6-14.6 years) actuarial 5-year OS was 32% (95% CI 22-42) and 5-year EFS was 31% (95% CI 21-41). Relapse rate was 24% (95% CI 15-33) at 2 and 5 years. Nonrelapse mortality was 29% (95% CI 20-38) at day 100 and 38% (95% CI 29-47) at 1 year. Cumulative incidence of acute (grade II-IV) and extensive chronic GVHD was 27% (95% CI 18-36) and 29% (95% CI 18-40), respectively. There was no statistically significant difference in OS (31 vs 32%, P=0.89) or relapse rates (17 vs 28%, P=0.22) for recipients of BM vs PBPC, respectively. These results confirm that patients with high-risk or advanced myeloid malignancies can achieve long-term survival following myeloablative allogeneic HCT with aggressive conditioning.

    View details for DOI 10.1038/bmt.2010.114

    View details for PubMedID 20498648

  • Chronic Graft-Versus-Host Disease Responds to Imatinib and Pre Transplant/Donor Anti-PDGFRA Antibodies Predict for Chronic Graft-Versus-Host Disease Development 52nd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) Chen, G. L., Arai, S., Flowers, M. E., Otani, J. M., Coram, M., McMillan, A., Shizuru, J. A., Johnston, L., Miklos, D. AMER SOC HEMATOLOGY. 2010: 958?58
  • Phase I/II Trial of GN-BVC, a Gemcitabine and Vinorelbine-Containing Conditioning Regimen for Autologous Hematopoietic Cell Transplantation in Recurrent and Refractory Hodgkin Lymphoma BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Arai, S., Letsinger, R., Wong, R. M., Johnston, L. J., Laport, G. G., Lowsky, R., Miklos, D. B., Shizuru, J. A., Weng, W., Lavori, P. W., Blume, K. G., Negrin, R. S., Horning, S. J. 2010; 16 (8): 1145-1154

    Abstract

    Autologous hematopoietic cell transplantation with augmented BCNU regimens is effective treatment for recurrent or refractory Hodgkin lymphoma (HL); however, BCNU-related toxicity and disease recurrence remain challenges. We designed a conditioning regimen with gemcitabine in combination with vinorelbine in an effort to reduce the BCNU dose and toxicity without compromising efficacy. In this phase I/II dose escalation study, the gemcitabine maximum tolerated dose (MTD) was determined at 1250 mg/m(2), and a total of 92 patients were treated at this dose to establish safety and efficacy. The primary endpoint was the incidence of BCNU-related toxicity. Secondary endpoints included 2-year freedom from progression (FFP), event-free survival (EFS), and overall survival (OS). Sixty-eight patients (74%) had 1 or more previously defined adverse risk factors for transplant (stage IV at relapse, B symptoms at relapse, greater than minimal disease pretransplant). The incidence of BCNU-related toxicity was 15% (95% confidence interval, 9%-24%). Only 2% of patients had a documented reduction in diffusing capacity of 20% or greater. With a median follow-up of 29 months, the FFP at 2 years was 71% and the OS at 2 years was 83%. Two-year FFP was 96%, 72%, 67%, and 14% for patients with 0 (n = 24), 1 (n = 37), 2 (n = 23), or 3 (n = 8) risk factors, respectively. Regression analysis identified PET status pretransplant and B symptoms at relapse as significant prognostic factors for FFP. This new transplant regimen for HL resulted in decreased BCNU toxicity with encouraging FFP and OS. A prospective, risk-modeled comparison of this new combination with other conditioning regimens is warranted.

    View details for DOI 10.1016/j.bbmt.2010.02.022

    View details for PubMedID 20197102

  • Long-term follow-up of patients with diffuse large B-cell non-Hodgkin's lymphoma receiving purged autografts after induction failure BONE MARROW TRANSPLANTATION Benjamin, J. E., Chen, G. L., Cao, T. M., Cao, P. D., Wong, R. M., Sheehan, K., Shizuru, J. A., JOHNSTON, L. J., Negrin, R. S., Lowsky, R., Laport, G. G. 2010; 45 (2): 303-309

    Abstract

    Patients with diffuse large B-cell lymphoma (DLBCL) who do not achieve a complete response to front-line combination chemotherapy are often offered high-dose therapy and autologous hematopoietic cell transplantation (AHCT). However, the efficacy of this therapy in this patient population has been addressed in only a few published reports. We retrospectively analyzed the outcomes of patients with a diagnosis of de novo DLBCL who underwent AHCT at our center between 1988 and 2002, and identified 43 consecutive patients who had not achieved a CR before AHCT, although most showed at least a partial response (PR) to either induction or subsequent salvage chemotherapy. A total of 15 patients received a conditioning regimen that included high-dose chemotherapy with fractionated TBI (FTBI), whereas 28 patients received high-dose chemotherapy only. All autografts were treated ex vivo with MoAbs and complement in an effort to remove any residual malignant B cells. A total of 33 (77%) patients achieved a CR after AHCT. With a median follow-up of 7.3 years, the 5-year OS was 69% and EFS was 59%. Four patients died from non-relapse mortality. By univariate analyses, the following characteristics did not significantly impact OS: disease stage at diagnosis, age-adjusted IPI (International Prognostic Index) score, age > or =40 years, earlier radiotherapy and the use of FTBI in the conditioning regimen. These results confirm the long-term efficacy of AHCT for patients with DLBCL after induction failure.

    View details for DOI 10.1038/bmt.2009.152

    View details for Web of Science ID 000274397400013

    View details for PubMedID 19597427

    View details for PubMedCentralID PMC2886804

  • A Dose Escalation Trial of Imatinib for Steroid Dependent Chronic Graft-Versus-Host Disease with Anti-PDGFRA Antibody Analysis 51st Annual Meeting and Exposition of the American-Society-of-Hematology Chen, G. L., Arai, S., Flowers, M. E., Otani, J., Cheng, E. C., McMillan, A., Weng, W., Shizuru, J., Johnston, L., Miklos, D. AMER SOC HEMATOLOGY. 2009: 1281?81
  • TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors BLOOD Kohrt, H. E., Turnbull, B. B., Heydari, K., Shizuru, J. A., Laport, G. G., Miklos, D. B., Johnston, L. J., Arai, S., Weng, W., Hoppe, R. T., Lavori, P. W., Blume, K. G., Negrin, R. S., Strober, S., Lowsky, R. 2009; 114 (5): 1099-1109

    Abstract

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

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

    View details for PubMedID 19423725

  • Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease BLOOD Martin, P. J., Storer, B. E., Rowley, S. D., Flowers, M. E., Lee, S. J., Carpenter, P. A., Wingard, J. R., Shaughnessy, P. J., Devetten, M. P., Jagasia, M., Fay, J. W., Van Besien, K., Gupta, V., Kitko, C., Johnston, L. J., Maziarz, R. T., Arora, M., Jacobson, P. A., Weisdorf, D. 2009; 113 (21): 5074-5082

    Abstract

    We conducted a double-blind, randomized multicenter trial to determine whether the addition of mycophenolate mofetil (MMF) improves the efficacy of initial systemic treatment of chronic graft-versus-host disease (GVHD). The primary endpoint was resolution of chronic GVHD and withdrawal of all systemic treatment within 2 years, without secondary treatment. Enrollment of 230 patients was planned, providing 90% power to observe a 20% difference in success rates between the 2 arms. The study was closed after 4 years because the interim estimated cumulative incidence of success for the primary endpoint was 23% among 74 patients in the MMF arm and 18% among 77 patients in the control arm, indicating a low probability of positive results for the primary endpoint after completing the study as originally planned. Analysis of secondary endpoints showed no evidence of benefit from adding MMF to the systemic regimen first used for treatment of chronic GVHD. The estimated hazard ratio of death was 1.99 (95% confidence interval, 0.9-4.3) among patients in the MMF arm compared with the control arm. MMF should not be added to the initial systemic treatment regimen for chronic GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00089141 on August 4, 2004.

    View details for DOI 10.1182/blood-2009-02-202937

    View details for Web of Science ID 000266404500011

    View details for PubMedID 19270260

    View details for PubMedCentralID PMC2686178

  • High-dose chemotherapy followed by stem cell rescue for high-risk germ cell tumors: the Stanford experience BONE MARROW TRANSPLANTATION Agarwal, R., Dvorak, C. C., Stockerl-Goldstein, K. E., Johnston, L., Srinivas, S. 2009; 43 (7): 547-552

    Abstract

    Germ cell tumors carry an excellent prognosis with platinum-based therapy upfront. The patients who either relapse or demonstrate refractoriness to platinum pose a challenge. There exist many reports in the literature on the use of high-dose chemotherapy and stem cell rescue improving the outcome in patients with relapsed germ cell tumors. However, the reports have great variability in the patient selection, prior treatments, the choice of the conditioning regimen and variability of the doses within the same regimen. In this report, we present 37 patients who underwent a uniform protocol of high-dose chemotherapy with stem cell rescue. Stem cell mobilization was performed with high-dose CY (4 g per m(2)) and we were able to collect adequate cells for marrow rescue in all patients. Patients received a high-dose regimen with etoposide (800 mg/m(2) per day) days -6, -5 and -4 as a continuous infusion, carboplatin (667 mg/m(2) per day) on days -6, -5 and -4 as a 1 h infusion, and CY (60 mg/kg per day) on days -3 and -2. In this high-risk group of patients, high-dose chemotherapy with autologous stem cell rescue led to a 3-year overall survival of 57% and a 3-year event-free survival of 49%. The results are reflective of a single procedure. No tandem transplants were performed. The treatment-related mortality was low at 3% in this heavily pretreated group.

    View details for DOI 10.1038/bmt.2008.364

    View details for Web of Science ID 000265005800005

    View details for PubMedID 18997833

  • Phase I/II Trial of a Novel Gemcitabine and Vinorelbine-Containing Conditioning Regimen in Autologous Hemotopoietic Cell Transplantation for High-Risk Recurrent and Refractory Hodgkin Lymphoma. 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium Arai, S., Letsinger, R., Johnston, L., Laport, G., Lowsky, R., Miklos, D., Shizuru, J., Weng, W., Wong, R., Lavori, P., Blume, K., Negrin, R., Horning, S. AMER SOC HEMATOLOGY. 2008: 765?66
  • Functional Control of CMV Reactivation Is Profoundly Influenced by CMV Serostatus after Nonmyeloablative Hematopoietic Cell Transplantation Following a TLI-ATG Preparative Regimen 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium Schaenman, J., Vana, M. L., Rhee, C., Wong, J., Navato, S., Johnston, L. J., Wong, R. M., Ho, D. Y., Brown, J. (. AMER SOC HEMATOLOGY. 2008: 780?80
  • Prophylactic Rituximab after Reduced Intensity Conditioning Transplantation Results in Low Chronic Gvhd 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium Arai, S., Sahaf, B., Jones, C., Zhender, J., Lowsky, R., Strober, S., Shizuru, J., Negrin, R., Johnston, L., Laport, G., Schaenman, J., Brown, J., Weng, W., Letsinger, R., Wong, R., Lavori, P., Miklos, D. AMER SOC HEMATOLOGY. 2008: 178?78
  • Acute graft-versus-host disease: differing risk with differing graft sources and conditioning intensity BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY Johnston, L. 2008; 21 (2): 177-192

    Abstract

    Acute graft-versus-host disease (aGVHD) is a constant component of allogeneic hematopoietic cell transplantation (HCT), with variations in incidence and severity affected by the graft source, human leukocyte antigen (HLA) compatibility, and the preparative regimen. The graft source - related versus unrelated donors, bone marrow (BM) versus peripheral blood (PB), umbilical cord blood (UCB) versus unrelated donor BM - are discussed in this review, as well as myeloablative versus reduced-intensity (RI) preparative regimens. Recent comparisons of matched related versus matched unrelated donor HCT support a minimal difference in aGVHD between these two donor sources. The use of BM versus mobilized PB in the matched related donor (MRD) setting has been compared in randomized as well as phase-II comparative clinical trials which support a slight increase in aGVHD in the adult population. Similar results have been seen in the unrelated donor (URD) setting, although based on minimal comparative data to date. Preliminary comparisons of UCB versus URD BM have shown a decreased incidence of aGVHD with UCB, despite increased HLA mismatching. Haploidentical HCT has continued to be explored, with limitations due to delayed immune reconstitution and disease relapse. Many reduced-intensity preparative regimens have been published, with a reduced or minimal difference in incidence of aGVHD when historically compared to myleoablative preparative regimens. More formal comparisons of the different graft sources as well as preparative regimen intensities will be required to determine a more accurate picture of the differences between these transplantation alternatives.

    View details for DOI 10.1016/j.beha.2008.02.006

    View details for Web of Science ID 000257005500008

    View details for PubMedID 18503985

  • Autologous cytokine-induced killer cells as post-transplant cellular immunotherapy 49th Annual Meeting of the American-Society-of-Hematology Arai, S., Sheehan, K., Moore, S., Laport, G., Johnston, L., Lowsky, R., Miklos, D., Goldstein, K., Weng, W., Shizuru, J., Horning, S., Negrin, R. AMER SOC HEMATOLOGY. 2007: 179A?179A
  • The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia BLOOD Oehler, V. G., Gooley, T., Snyder, D. S., Johnston, L., Lin, A., Cummings, C. C., Chu, S., Bhatia, R., Forman, S. J., Negrin, R. S., Appelbaum, F. R., Radich, J. P. 2007; 109 (4): 1782-1789

    Abstract

    The impact of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) on subsequent allogeneic transplantation is uncertain. To better understand this relationship, we retrospectively compared 145 patients with CML receiving IM for a minimum of 3 months before allogeneic hematopoietic cell transplantation (HCT) to 231 patients with CML who did not. IM treatment was associated with no increase in early hepatotoxicity or engraftment delay after HCT compared with the historical cohort. In addition, there was no statistically significant difference in the IM-treated cohort compared with the historical cohort with regard to overall survival, disease-free survival, relapse, and nonrelapse mortality. For chronic-phase (CP) patients, IM response prior to HCT was associated with post-HCT outcome. Patients who underwent transplantation in CP with a suboptimal response or a loss of response on IM had a statistically significant higher hazard of mortality when compared with CP patients who achieved a complete cytogenetic response (CCR) or major cytogenetic response (MCR) on IM (HR=5.31, 95% confidence interval [CI] 1.13-25.05, P=.03). These data indicate that pre-HCT IM is not associated with increased transplant-related morbidity (TRM) or poorer outcomes. However, patients with a suboptimal or loss of IM response before HCT do worse, suggesting a more aggressive disease course for these patients.

    View details for Web of Science ID 000244219400061

    View details for PubMedID 17062727

    View details for PubMedCentralID PMC1794075

  • Clinical outcomes following allogeneic hematopoietic cell transplantation (HCT) using nonmyeloablative host conditioning with total lymphoid irradiation and anti-thymocyte globulin confirm a low incidence of graft versus host disease (GVHD) and retained graft anti-tumor activity. 48th Annual Meeting of the American-Society-of-Hematology Lowsky, R., Stockert-Goldstein, K., Laport, G., Miklos, D., Arai, S., Shizuru, J., Johnston, L., Blume, K., Negrin, R., Strober, S. AMER SOC HEMATOLOGY. 2006: 182A?182A
  • Membranous glomerulonephritis and nephrotic syndrome as a late manifestation of chronic graft-versus-host reaction following allogeneic transplantation for hematologic malignancy. Ahmad, B., Stehr, B., Johnston, L., Smith, E., Nademanee, A. P., Parker, P., Negrin, R., Forman, S. J. AMER SOC HEMATOLOGY. 2006: 819A?820A
  • High dose therapy and autologous hematopoietic cell transplantation for primary refractory diffuse large cell non-Hodgkin's lymphoma. 48th Annual Meeting of the American-Society-of-Hematology Cao, T. M., Stockerl-Goldstein, K. E., Cao, P. D., Laport, G. G., Sheehan, K., Shizuru, J. A., Johnston, L. J., Negrin, R. S., Lowsky, R. AMER SOC HEMATOLOGY. 2006: 462B?463B
  • Cytokine induced killer (CIK) cells as post-transplant immunotherapy following allogeneic hematopoietic cell transplantation. 48th Annual Meeting of the American-Society-of-Hematology Laport, G. G., Sheehan, K., Lowsky, R., Shizuru, J. A., Stockerl-Goldstein, K., Johnston, L. J., Miklos, D., Arai, S., Baker, J., Negrin, R. S. AMER SOC HEMATOLOGY. 2006: 126A?126A
  • Rituximab infusion two months after nonmyeloablative transplantation maintains B-cell disease control with minimal GVHD. 48th Annual Meeting of the American-Society-of-Hematology Arai, S., Sahaf, B., Jones, C., Zehnder, J., Lowsky, R., Strober, S., Shizuru, J., Negrin, R., Johnston, L., Laport, G., Goldstein, K., Brown, J. (., Miklos, D. AMER SOC HEMATOLOGY. 2006: 823A?823A
  • 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 PubMedID 16785059

  • Protective conditioning for acute graft-versus-host disease NEW ENGLAND JOURNAL OF MEDICINE Lowsky, R., Takahashi, T., Liu, Y. P., Dejbakhsh-Jones, S., GRUMET, F. C., Shizuru, J. A., Laport, G. G., Stockerl-Goldstein, K. E., JOHNSTON, L. J., Hoppe, R. T., Bloch, D. A., Blume, K. G., Negrin, R. S., Strober, S. 2005; 353 (13): 1321-1331

    Abstract

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

    View details for PubMedID 16192477

  • Treatment of verruca vulgaris with topical cidofovir in an immunlocompromised patient: a case report and review of the literature TRANSPLANT INFECTIOUS DISEASE Cha, S., Johnston, L., Natkunam, Y., Brown, J. 2005; 7 (3-4): 158-161

    Abstract

    Lesions caused by verrucus vulgaris are commonly refractory to therapy and may become large, painful, or disfiguring in immunocompromised patients. Cidofovir is a potent nucleoside analog antiviral agent shown to have in vitro and in vivo activity against a broad spectrum of DNA viruses. We report a successful use of topical cidofovir to treat verruca vulgaris lesions in a highly immunocompromised patient, who was not considered a candidate for conventional therapy.

    View details for Web of Science ID 000236936200012

    View details for PubMedID 16390407

  • A phase I/II study of mycophenolate mofetil in combination with cyclosporine for prophylaxis of acute graft-versus-host disease after myeloablative conditioning and allogeneic hematopoietic cell transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Nash, R. A., Johnston, L., Parker, P., McCune, P. S., Storer, B., Slattery, J. T., Furlong, T., Anasetti, C., Appelbaum, F. R., Lloid, M. E., Deeg, H. J., Kiem, H. P., Martin, P. J., Schubert, M. M., Witherspoon, R. P., Forman, S. J., Blume, K. G., Storb, R. 2005; 11 (7): 495?505

    Abstract

    Abstract In a phase I/II study, the combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) was investigated as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and hematopoietic cell transplantation from an HLA-matched sibling donor. In phase I, 3 groups, each with 10 or 11 patients, received MMF (15 mg/kg) from day 0 to day 27 at decreasing dose intervals of every 12, 8, and 6 hours to determine a safe and effective total daily dose. At the 45 mg/kg/d dosage level, 4 of 11 patients developed only grade II GVHD, and a concentration at steady state of mycophenolic acid (the active moiety of MMF) consistent with a therapeutic range described for solid-organ transplantation was achieved. There was a suggestion of increased toxicity without improved efficacy at the 60 mg/kg/d dosage level. Accordingly, the 45 mg/kg/d dosage was therefore selected for phase II, and another 15 patients were added to this group from the phase I study (n=26). The concentrations at steady state for this dosage at days 0, 6, 13, 20, and 27 were 2.73, 3.02, 3.20, 2.62, and 2.64 microg/mL, respectively. No toxicities were attributed to MMF at this dose. The median time to engraftment after hematopoietic cell transplantation was 15 days (range, 10-20 days). The incidence of acute GVHD was 62%, which was comparable to a group of historical controls receiving CSP and methotrexate (MTX) for GVHD prophylaxis. Although a significant improvement in the prevention of GVHD was not suggested, compared with CSP and MTX, MMF in combination with CSP could be considered in cases in which MTX is contraindicated.

    View details for DOI 10.1016/j.bbmt.2005.03.006

    View details for Web of Science ID 000230425500002

    View details for PubMedID 15983549

  • A phase II multicenter study of visilizumab, humanized anti-CD3 antibody, to treat steroid-refractory acute graft-versus-host disease BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Carpenter, P. A., Lowder, J., Johnston, L., Frangoul, H., Khoury, H., Parker, P., Jerome, K. R., McCune, J. S., Storer, B., Martin, P., Appelbaum, F., Abonour, R., Westervelt, P., Anasetti, C. 2005; 11 (6): 465?71

    Abstract

    Results of a previous phase I study suggested that a single 3 mg/m2 dose of the humanized non-FcR-binding anti-CD3 monoclonal antibody visilizumab (Nuvion) was well tolerated and had efficacy for the treatment of steroid-refractory acute graft-versus-host disease (GVHD). We now report results of a multicenter phase II study in which visilizumab was given to 44 participants with steroid-refractory acute GVHD. Eighty-two percent of the participants had visceral involvement, and 86% had overall grade III or IV acute GVHD at study entry. The respective complete and overall response rates were 14% and 32% at 42 days. Plasma Epstein-Barr virus DNA increased to more than 1000 copies per milliliter in 19 subjects. Seventeen received rituximab, and no fatal lymphoproliferative disorders were observed. Survival at 180 days was 32% (95% confidence interval, 18%-46%). The administration of visilizumab as used in this study seems to be sufficiently safe and effective to warrant further assessment for treatment or prevention of GVHD.

    View details for DOI 10.1016/j.bbmt.2005.03.002

    View details for Web of Science ID 000230059800007

    View details for PubMedID 15931635

  • Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8(+) T-cell dose BLOOD Cao, T. M., Shizuru, J. A., Wong, R. M., Sheehan, K., Laport, G. G., Stockerl-Goldstein, K. E., JOHNSTON, L. J., Stuart, M. J., GRUMET, F. C., Negrin, R. S., Lowsky, R. 2005; 105 (6): 2300-2306

    Abstract

    The influence of graft composition on clinical outcomes after reduced-intensity conditioning is not well-characterized. In this report we prospectively enumerated CD34+, CD3+, CD4+, and CD8+ cell doses in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) allografts in 63 patients who received transplants following non-myeloablative conditioning with total body irradiation 200 cGy plus fludarabine as treatment for malignant diseases. Donors were HLA-identical siblings (n = 38) or HLA-matched unrelated individuals (n = 25). By univariate analyses G-PBMC CD8+ T-cell dose in at least the 50th percentile favorably correlated with full donor blood T-cell chimerism (P = .03), freedom from progression (P = .001), and overall survival (P = .01). No G-PBMC cell dose influenced grade II to IV acute or extensive chronic graft-versus-host disease. In multivariate analysis only G-PBMC CD8+ T-cell dose (P = .003; RR = 0.2, 95% CI = 0.1-0.6) was associated with improved freedom from progression. Infusion of low G-PBMC CD8+ T-cell dose for reduced-intensity allografting may adversely affect T-cell engraftment and survival outcome.

    View details for DOI 10.1182/blood-2004-04-1473

    View details for PubMedID 15572597

  • CD34, CD49 and CD8 cell doses do not influence engraftment, graft-versus-host disease, or survival following myeloablative human leukocyte antigen-identical peripheral blood allografting for hematologic malignancies EXPERIMENTAL HEMATOLOGY Cao, T. M., Wong, R. M., Sheehan, K., Laport, G. G., Stockerl-Goldstein, K. E., JOHNSTON, L. J., Shizuru, J. A., Negrin, R. S., Lowsky, R. 2005; 33 (3): 279-285

    Abstract

    Optimal granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cell (G-PBMC) graft compositions for myeloablative allogeneic hematopoietic cell transplantation (AHCT) have not been identified. G-PBMC cell contents were analyzed for influence on outcomes.Human leukocyte antigen(HLA)-identical related donor AHCT was used to treat 101 patients with hematologic malignancies at a single institution between 1995 and 2002. CD34+, CD3+, CD4+, and CD8+ cell doses were enumerated by flow cytometry and evaluated by univariate analysis.Categorized by the median of cell doses infused, no G-PBMC cell dose significantly correlated with neutrophil and platelet engraftment. Incidence of grade II to IV acute graft-versus-host disease (GVHD) was 24.6% (95% confidence interval [CI]: 15.9-33.3) and was not significantly influenced by evaluated G-PBMC cell doses. With a median follow-up time of 18 months for surviving patients, estimates for extensive chronic GVHD was 43.8% (95% CI: 31.4-56.2), for freedom from progression was 69.5% (95% CI: 58.1-80.9), and for overall survival was 46.9% (95% CI: 35.5-58.3). CD34+, CD3+, CD4+, and CD8+ cell doses were not significantly predictive of extensive chronic GVHD, freedom from progression or overall survival. Additionally, comparing patients receiving the upper versus lower 33rd percentiles of CD34+ cell dose, associations with extensive chronic GVHD remained insignificant (p=0.21; relative risk (RR)=1.7; 95% CI: 0.7-3.9).G-PBMC graft content does not influence outcomes after myeloablative AHCT. In particular, no significant association between extensive chronic GVHD was identified with any G-PBMC cell dose, including CD34.

    View details for DOI 10.1016/j.exphem.2004.12.004

    View details for PubMedID 15730851

  • Rapamycin (sirolimus) for treatment of chronic graft-versus-host disease BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Johnston, L. J., Brown, J., Shizuru, J. A., Stockerl-Goldstein, K. E., Stuart, M. J., Blume, K. G., Negrin, R. S., Chao, N. J. 2005; 11 (1): 47-55

    Abstract

    We conducted a phase II trial in 19 chronic graft-versus-host disease (cGVHD) patients with rapamycin, calcineurin inhibitors, and prednisone with the goals of controlling cGVHD, reducing prednisone use, and defining the safety of this regimen. Rapamycin was begun as second-line (n = 9) or more than second-line (n = 10) therapy. With a median follow-up of 42 months, 16 patients were evaluable for response. Nine patients discontinued rapamycin because of poor compliance/patient request (n = 2) or an adverse event (n = 7), 3 of whom were not evaluable because of withdrawal at < or =1 month or noncompliance. The adverse events included serum creatinine > or =2.4 mg/dL (n = 4), hemolytic uremic syndrome (n = 2), and relapse of malignancy (n = 1). Fifteen of 16 evaluable patients had a clinical response. Five of the 16 discontinued the drug, and 1 died of relapsed leukemia. Of the 10 patients who continued rapamycin, 2 discontinued and 1 successfully tapered all systemic immunosuppression. Three of the 10 developed progressive cGVHD with tapering immunosuppression; all responded to resumption of prior medications. Four of the 10 patients required alternate therapy for persistent or progressive cGVHD while receiving rapamycin; prednisone was discontinued (n = 2) or tapered at the time of progressive disease (n = 2). Seventeen of 19 original patients were alive. One death was due to relapsed malignancy, and 1 was due to congestive heart failure. In this report of rapamycin as cGVHD therapy, there is evidence of rapamycin's efficacy. Given the significant toxicities described, investigation of altered administration of rapamycin and calcineurin inhibitors should be pursued in future cGVHD trials.

    View details for DOI 10.1016/j.bbmt.2004.10.004

    View details for PubMedID 15625544

  • Engraftment and survival following non-myeloablative allogeneic peripheral blood hematopoietic cell transplantation for malignant diseases is affected by CD8(+) T-cell dose. 46th Annual Meeting of the American-Society-of-Hematology Cao, T. M., Shizuru, J. A., Wong, R. M., Sheehan, K., Laport, G. G., Stockerl-Goldstein, K. E., JOHNSTON, L. J., Stuart, M. J., Brown, J. M., GRUMET, F. C., Negrin, R. S., Lowsky, R. AMER SOC HEMATOLOGY. 2004: 56A?56A
  • Treatment of acute leukemia with idarubicin, etoposide and cytarabine (IDEA). A randomized study of etoposide schedule CANCER CHEMOTHERAPY AND PHARMACOLOGY Damon, L. E., JOHNSTON, L. J., Ries, C. A., Rugo, H. S., Case, D., Ault, K., Linker, C. A. 2004; 53 (6): 468-474

    Abstract

    The differences in toxicity of etoposide following continuous or bolus infusion are unknown.We studied the schedule-dependent toxicity of high-dose etoposide when combined with high-dose cytarabine and idarubicin (IDEA) in 138 patients with acute leukemia. Four groups of patients were studied: group I, relapse; group II, secondary acute myeloid leukemia (AML); group III, de novo AML, age >60 years; and group IV, induction failure or blast crisis of myeloproliferative syndrome. Treatment for groups I-III was idarubicin 8 mg/m(2) per day days 1-3, cytarabine 2000 mg/m(2) once a day days 1-6, and etoposide 1600 mg/m(2) total dose. Group IV treatment differed by cytarabine given twice daily days 1-6. Patients were randomized to etoposide as a continuous infusion days 1-6 or as a bolus infusion over 10 h on day 7.Continuous infusion etoposide produced significantly more oral mucositis than bolus etoposide. In groups I-III, comparing continuous and bolus etoposide, there was a median of 3 vs 0 days of grade 2 or more oral mucositis (P<0.0001) and 13.5 vs 0 days of total parenteral nutrition (TPN) (P=0.0003). Group IV patients had a median 7 vs 0 days of grade 2 or more oral mucositis (P<0.01) and 21 vs 7 days of TPN (P<0.003), respectively. There were no differences in hematologic recovery, length of hospital stay, complete remission rate or overall survival between the two etoposide schedules. Of groups I-III patients, 51% achieved complete remission, and 11% died from treatment-related complications.The toxicity profile of high-dose etoposide is schedule-dependent with prolonged exposure producing significantly more non-hematologic toxicity.

    View details for DOI 10.1007/s00280-003-0758-x

    View details for Web of Science ID 000221344600002

    View details for PubMedID 15138711

  • Non-myeloablative conditioning with total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) for allogeneic hematopoietic cell transplantation (HCT) results in high levels of regulatory natural killer T cells and low incidences of acute GVHD and tumor relapse. 45th Annual Meeting and Exhibition of the American-Society-of-Hematology Lowsky, R., Jones, S. D., Mitra, S., Shizuru, J. A., Laport, G. G., Stockerl-Goldstein, K., JOHNSTON, L. J., Stuart, M. J., Herzenberg, L. A., Hoppe, R. T., Blume, K. G., Negrin, R. S., Strober, S. AMER SOC HEMATOLOGY. 2003: 152A?153A
  • A phase II, multicenter study of visilizumab, humanized anti-CD3 antibody, to treat steroid refractory acute GVHD. Carpenter, P., Lowder, J., Johnston, L., Frangoul, H., Khoury, H., Parker, P., Abonour, R., Westervelt, P., Dansey, R., Richard, S., Jerome, K., Corey, L., Anasetti, C. AMER SOC HEMATOLOGY. 2003: 712A
  • A phase I/II study of mycophenolate mofetil (MMF) in combination with cyclosporine (CSP) for prophylaxis of graft versus host disease (GVHD) after myeloablative conditioning and allogeneic hematopoietic cell transplantation (HCT): Dose escalation of MMF. Nash, R. A., Johnston, L., Parker, P. M., Slattery, J. T., Storer, B., Furlong, T., Anasetti, C., Appelbaum, F. R., Lloid, C. M., Blume, K., Deeg, H. J., Forman, S. J., Kiem, H. P., Martin, P. J., Schubert, M., Witherspoon, R. P., Storb, R. AMER SOC HEMATOLOGY. 2003: 240A
  • Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin's lymphoma; Blood Steven M Horwitz, Robert S Negrin, Karl G Blume, Sheila Breslin, Monic J Stuart, Keith E Stockerl-Goldstein, Laura J Johnston, Ruby M Wong, Judith A Shizuru, Sandra J Horning. 2003; 2003: 1257
  • Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial BLOOD Flowers, M. E., Parker, P. M., JOHNSTON, L. J., Matos, A. V., Storer, B., Bensinger, W. I., STORB, R., Appelbaum, F. R., Forman, S. J., Blume, K. G., Martin, P. J. 2002; 100 (2): 415-419

    Abstract

    In a previous multicenter phase III trial comparing peripheral blood stem cell transplantation (PBSCT) to bone marrow transplantation (BMT) from HLA-matched related donors, we found no statistically significant difference in the cumulative incidence of clinical extensive chronic graft-versus-host disease (GVHD) in the 2 groups. We have analyzed the results in more detail to determine whether the clinical characteristics of chronic GVHD after PBSCT might be distinct from those that occur after BMT. Clinical extensive chronic GVHD developed in 39 of 63 recipients of PBSCs and in 32 of 63 BM recipients who were alive and free of malignancy at day 100 after the transplantation. No significant differences were found in the time and type of onset of clinical extensive chronic GVHD or in the frequency of complications associated with severe morbidity. Involvement of skin and female genital tract was more frequent in PBSC recipients than in BM recipients. The cumulative incidence of chronic GVHD at 3 years was similar in the 2 groups, but the number of successive treatments needed to control chronic GVHD was higher after PBSCT than after BMT (P =.03), and the duration of glucocorticoid treatment was longer after PBSCT compared to BMT (P =.03). These results suggest that chronic GVHD after PBSCT may be more protracted and less responsive to current treatment than chronic GVHD after BMT. Assessment of the overall benefits of PBSCT compared to BMT will require continued long-term follow up of morbidity associated with chronic GVHD.

    View details for Web of Science ID 000176741200006

    View details for PubMedID 12091330

  • Phase II trial of rituximab as adjuvant therapy to high dose chemotherapy and peripheral blood stem cell transplantation for relapsed and refractory aggressive non-Hodgkin's lymphomas. Horwitz, S. M., Negrin, R. S., Stockerl-Goldstein, K. E., JOHNSTON, L. J., Shizuru, J. A., Stuart, M. J., Breslin, S., Blume, K. G., Horning, S. J. AMER SOC HEMATOLOGY. 2001: 862A?862A
  • 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

  • Adjuvant rituximab after autologous peripheral blood stem cell transplant (APBSCT) results in delayed immune reconstitution without increase in infectious complications. Horwitz, S. M., Breslin, S., Negrin, R. S., Stockerl-Goldstein, K. E., JOHNSTON, L. J., Shizuru, J. A., Taylor, T., Brown, B. W., Blume, K. G., Horning, S. J. AMER SOC HEMATOLOGY. 2000: 384A?384A
  • High dose therapy and autologous hematopoietic cell transplantation for follicular lymphoma beyond first remission: The Stanford University experience. Cao, T. M., Negrin, R. S., Hu, W. W., JOHNSTON, L. J., Taylor, T. L., Shizuru, J. A., Brown, B. W., Horning, S. J., Blume, K. G., Stockerl-Goldstein, K. E. AMER SOC HEMATOLOGY. 2000: 482A?482A
  • Increased transplant-related mortality following high-dose sequential chemotherapy and autologous hematopoietic cell transplantation (AHCT) using the Ceprate SC stem cell concentration system for multiple myeloma (MM). Stockerl-Goldstein, K. E., Brown, J. M., O'Brien, R. M., Negrin, R. S., Hu, W. W., JOHNSTON, L. J., Shizuru, J. A., Taylor, T. L., Blume, K. G. AMER SOC HEMATOLOGY. 1999: 608A?608A
  • So you want to build a Web site + A blueprint for museum professionals MUSEUM NEWS Johnston, L., JONESGARMIL, K. 1997; 76 (1): 41-44

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