Bio

Clinical Focus


  • Blood and Marrow Transplantation
  • Hematology
  • Cancer > Hematology
  • Cancer > Blood and Marrow Transplant

Academic Appointments


Honors & Awards


  • K23-“Reduce GVHD and Relapse using Ex-Vivo Expanded Allogeneic Cell Therapy”, NIH (2003-2008)
  • “A phase I/II study of post-transplant autologous CIK cells for high-risk hematologic malignancies”, Cancer Treatment Research Foundation (2005-2009)

Professional Education


  • Residency:Strong Memorial Hospital (1995) NY
  • Fellowship:John Hopkins Hospital (1999) MD
  • Fellowship:Mount Sinai Medical Center (1998) NY
  • Internship:Strong Memorial Hospital (1993) NY
  • Medical Education:Dartmouth Medical School (1991) NH
  • MS, Stanford University, Epidemiology (2006)
  • MD, Dartmouth Medical School

Research & Scholarship

Current Research and Scholarly Interests


Research interest in utilizing post-transplant adoptive cellular immunotherapy to reduce GVHD and relapse in patients with high risk hematologic malignancies.

Clinical Trials


  • 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. 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 work well, such as determining the following: - how well recipients recover from their transplant - how recovery after a transplant can be improved - how access to transplant for different groups of patients can be improved - how well donors recover from the collection procedures

    View full details

  • Imatinib and Rituximab in Treating Cutaneous Sclerosis in Patients With Chronic Graft-Versus-Host Disease 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • Post T-plant Infusion of Allogeneic Cytokine Induced Killer Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders Recruiting

    This study examines CIK (Cytokine Induced Killer Cells) as Consolidative Therapy after Non-Myeloablative Allogeneic Transplantation.

    View full details

  • 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 MMF vs. placebo to systemic corticosteroids as initial therapy for acute 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.

    View full details

  • Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia Not Recruiting

    This phase I/II trial is studying the side effects and best way to give nilotinib when given together with 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

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

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

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

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • Vaccine Therapy for Multiple Myeloma Utilizing Idiotype-Pulsed Allogeneic Dendritic Cells Not Recruiting

    Patients with Multiple myeloma who have undergone non-myeloablative allogeneic stem cell transplant will receive 6 vaccinations of donor derived dendritic cells combined with specific protein produced by multiple myeloma.

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

    View full details

  • Intravenous Administration of RGI-2001 in Patient Undergoing Allogenic Hematopoietic Stem Cell Transplantation (AHSCT) 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.

    View full details

  • Phase I/II 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 addback) 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.

    View full details

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

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

    View full details

  • 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.

    View full details

  • 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.

    View full details

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

    We hypothesize the addition of rituximab to prednisone for the initial treatment of chronic GVHD will increase the overall response rate, and 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.

    View full details

  • Double Cord Versus Haploidentical (Blood and Marrow Transplant Clinical Trials Network #1101) 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.

    View full details

  • Defibrotide for Patients With Hepatic Veno-occlusive Disease: A Treatment IND Study 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.

    View full details

  • 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 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.

    View full details

  • 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.

    View full details

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

    To determine if Rituximab administered after allogeneic transplantation decreases the incidence of chronic GvHD

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

    View full details

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

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

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Palifermin (rHuKGF) in the Reduction of Acute Graft Versus Host Disease in Subjects With Hematologic Malignancies Undergoing Allogeneic Marrow/PBPC Transplantation Not Recruiting

    The purpose of this study is to reduce the incidence of grade 2-4 GVHD and WHO grades 3-4 Oral Mucositis.

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

    View full details

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

    GVHD prophylaxis of sirolimus and mycophenolate mofetil for patients undergoing matched related allogeneic transplant for acute and chronic leukemia, MDS, high risk NHL and HL

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

    View full details

  • Ph II 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.

    View full details

  • 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.

    View full details

  • 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.

    View full details

  • Comparing Peripheral Blood Stem Cell Transplantation Versus Bone Marrow Transplantation in Individuals With Hematologic Cancers 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.

    View full details

  • 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.

    View full details

  • Allogeneic Transplantation Using TL1 & 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 (GV/HD) occurs.

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

    View full details

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

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

    View full details

  • Sirolimus/Tacrolimus Versus Tacrolimus/Methotrexate for Preventing Graft-Versus-Host Disease (GVHD) 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.

    View full details

  • Bone Marrow Grafting for Leukemia and Lymphoma Recruiting

    Bone Marrow Grafting for Leukemia and Lymphoma

    View full details

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

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

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

    View full details

Teaching

2013-14 Courses


Graduate and Fellowship Programs


Publications

Journal Articles


  • The prognostic value of diagnosing concurrent multiple myeloma in immunoglobulin light chain amyloidosis BRITISH JOURNAL OF HAEMATOLOGY Dinner, S., Witteles, W., Witteles, R., Lam, A., Arai, S., Lafayette, R., George, T. I., Schrier, S. L., Liedtke, M. 2013; 161 (3): 367-372

    Abstract

    The prevalence and prognostic value of a concomitant diagnosis of symptomatic or asymptomatic multiple myeloma (MM), as defined by the current International Myeloma Working Group (IMWG) criteria, in patients with immunoglobulin light chain amyloidosis (AL), are unknown. We studied 46 consecutive patients with AL who underwent quantification of serum M-protein and clonal bone marrow plasma cells, as well as a comprehensive evaluation for end organ damage by MM. Using standard morphology and CD138 immunohistochemical staining, 57% and 80% of patients were found to have concomitant MM, respectively. Nine patients exhibited end organ damage consistent with a diagnosis of symptomatic MM. While overall survival was similar between AL patients with or without concurrent myeloma (1-year overall survival 68% vs. 87%; P = 0.27), a diagnosis of symptomatic myeloma was associated with inferior outcome (1-year overall survival 39% vs. 81%; P = 0.005). Quantification of bone marrow plasma cells by both standard morphology and CD138 immunohistochemistry identified a much higher prevalence of concurrent MM in patients with AL than previously reported. Evaluation of bone marrow plasma cell infiltration and presence of myeloma associated end organ damage could be clinically useful for prognostication of patients with AL.

    View details for DOI 10.1111/bjh.12269

    View details for Web of Science ID 000317602300009

    View details for PubMedID 23432783

  • H-Y antigen-binding B cells develop in male recipients of female hematopoietic cells and associate with chronic graft vs. host disease PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Sahaf, B., Yang, Y., Arai, S., Herzenberg, L. A., Herzenberg, L. A., Miklos, D. B. 2013; 110 (8): 3005-3010

    Abstract

    B cells are known to play an important role in pathogenesis of human chronic graft vs. host disease (cGVHD). Our group has previously shown that IgG allo-antibodies recognize Y chromosome-encoded proteins (H-Y) and a dominant H-Y epitope, DEAD box protein (DBY-2) detectable 6-12 mo after transplant in male patients who receive grafts from female donors (F?M) hematopoietic cell transplantation (HCT). Here we present FACS studies of peripheral blood mononuclear cells collected 6 mo after transplant showing that 16 of 28 (57%) F?M HCT patients have circulating donor B cells that express B-cell receptor (mainly IgM and Ig?) specific for DBY-2. The detection of these DBY-2 B cells 6 mo after HCT are associated with cGVHD development (P = 0.004). Specifically, 15 of 16 F?M with DBY-2 B cells developed cGVHD. In contrast, cGVHD developed in only 5 of the 12 who did not have DBY-2 B cells detected. This demonstrates circulating human B cells binding an alloantigen (DBY-2) and that these DBY-2-specific B cells appear before development of cGVHD in roughly half of the F?M patients. Our study suggests that detection of anti-DBY-2 B cells may predict cGVHD and that this prediction may have clinical utility. Validation of this hypothesis will require larger prospective studies.

    View details for DOI 10.1073/pnas.1222900110

    View details for Web of Science ID 000315954400081

    View details for PubMedID 23382226

  • 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 Web of Science ID 000307398700030

    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

  • Heart transplantation and cardiac amyloidosis: Approach to screening and novel management strategies JOURNAL OF HEART AND LUNG TRANSPLANTATION Varr, B. C., Liedtke, M., Arai, S., Lafayette, R. A., Schrier, S. L., Witteles, R. M. 2012; 31 (3): 325-331

    Abstract

    Limited data exist regarding screening methods and outcomes for orthotopic heart transplantation (OHT) in cardiac amyloidosis. As a result, uncertainty exists over the best approach to OHT for cardiac amyloidosis and for the timing of critical post-transplant therapies. This article reviews 6 patients who underwent OHT for cardiac amyloidosis at the Stanford University Amyloid Center from 2008 to present. All patients with light-chain amyloidosis received chemotherapy in the interval between OHT and autologous hematopoietic stem cell transplant. Five patients remain alive up to 25 months after OHT, without evidence of recurrent cardiac amyloid deposition. A novel strategy of OHT, followed by light-chain suppressive chemotherapy before autologous hematopoietic stem cell transplant, is feasible for patients with light-chain amyloidosis.

    View details for DOI 10.1016/j.healun.2011.09.010

    View details for Web of Science ID 000300806500015

    View details for PubMedID 22051505

  • 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 Web of Science ID 000296829000016

    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

  • Global and organ-specific chronic graft-versus-host disease severity according to the 2005 NIH Consensus Criteria BLOOD Arai, S., Jagasia, M., Storer, B., Chai, X., Pidala, J., Cutler, C., Arora, M., Weisdorf, D. J., Flowers, M. E., Martin, P. J., Palmer, J., Jacobsohn, D., Pavletic, S. Z., Vogelsang, G. B., Lee, S. J. 2011; 118 (15): 4242-4249

    Abstract

    In 2005, the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD proposed a new scoring system for individual organs and an algorithm for calculating global severity (mild, moderate, severe). The Chronic GVHD Consortium was established to test these new criteria. This report includes the first 298 adult patients enrolled at 5 centers of the Consortium. Patients were assessed every 3-6 months using standardized forms recommended by the Consensus Conference. At the time of study enrollment, global chronic GVHD severity was mild in 10% (n = 32), moderate in 59% (n = 175), and severe in 31% (n = 91). Skin, lung, or eye scores determined the global severity score in the majority of cases, with the other 5 organs determining 16% of the global severity scores. Conventional risk factors predictive for onset of chronic GVHD and nonrelapse mortality in people with chronic GVHD were not associated with NIH global severity scores. Global severity scores at enrollment were associated with nonrelapse mortality (P < .0001) and survival (P < .0001); 2-year overall survival was 62% (severe), 86% (moderate), and 97% (mild). Patients with mild chronic GVHD have a good prognosis, while patients with severe chronic GVHD have a poor prognosis. This study was registered at www.clinicaltrials.gov as no. NCT00637689.

    View details for DOI 10.1182/blood-2011-03-344390

    View details for Web of Science ID 000296282200035

    View details for PubMedID 21791424

  • 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 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 Web of Science ID 000287190700004

    View details for PubMedID 20498648

  • Complete donor T-cell engraftment 30 days after allogeneic transplantation predicts molecular remission in high-risk chronic lymphocytic leukaemia BRITISH JOURNAL OF HAEMATOLOGY Jones, C. D., Arai, S., Lowsky, R., Tyan, D. B., Zehnder, J. L., Miklos, D. B. 2010; 150 (5): 637-639
  • 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 Web of Science ID 000280137800013

    View details for PubMedID 20197102

  • Rituximab in hematopoietic cell transplantation EXPERT OPINION ON BIOLOGICAL THERAPY Arai, S., Miklos, D. B. 2010; 10 (6): 971-982

    Abstract

    The success of rituximab therapy in managing B cell malignancies supports its widespread application in both autologous and allogeneic hematopoietic cell transplantation.We searched the PubMed database using the terms rituximab, stem cell transplant, autologous, or allogeneic and limited the search to clinical trials in English. In total, 92 trials were identified and 16 were reviewed in detail for significance of rituximab intervention. In this review, we will examine rituximab's emerging roles in: i) in vivo graft purging; ii) maintenance following autologous transplantation; iii) allogeneic transplant conditioning; and iv) the rationale for its use in the treatment/prevention of chronic graft-versus-host disease and post-transplant lymphoproliferative disorder.The reader will gain an understanding of the use of rituximab not only in transplants for B cell malignancies, but also its extension to other diseases where we are learning that B cells are involved in the pathogenesis.With rituximab firmly established in the non-transplant therapy of B cell malignancies, the new challenge in transplantation is how to incorporate the drug for optimum efficacy in those patients coming to transplant with relapse after rituximab-containing therapy.

    View details for DOI 10.1517/14712598.2010.485982

    View details for Web of Science ID 000277392300011

    View details for PubMedID 20420511

  • 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 Web of Science ID 000268491100025

    View details for PubMedID 19423725

  • Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial CYTOTHERAPY Arai, S., Meagher, R., Swearingen, M., Myint, H., Rich, E., Martinson, J., Klingemann, H. 2008; 10 (6): 625-632

    Abstract

    Renal cell cancer and malignant melanoma are two types of cancer that are responsive to immunotherapy. In this phase I dose-escalation study, the feasibility of large-scale expansion and safety of administering ex vivo-expanded NK-92 cells as allogeneic cellular immunotherapy in patients with refractory renal cell cancer and melanoma were determined.Twelve patients (aged 31-74 years) were enrolled, three per cohort at cell dose levels of 1x10(8)/m(2), 3x10(8)/m(2), 1x10(9)/m(2) and 3x10(9)/m(2). One treatment course consisted of three infusions. Eleven patients had refractory metastatic renal cell cancer; one patient had refractory metastatic melanoma.The NK-92 cells were expanded in X-Vivo 10 serum-free media supplemented with 500 U/mL Proleukin recombinant human interleukin-2 (rhIL-2), amino acids and 2.5% human AB plasma. Final yields of approximately 1x10(9) cells/culture bag (218-250xexpansion) over 15-17 days were achievable with >or=80% viability. Infusional toxicities of NK-92 were generally mild, with only one grade 3 fever and one grade 4 hypoglycemic episode. All toxicities were transient, resolved and did not require discontinuation of treatment. One patient was alive with disease at 4 years post-NK-92 infusion. The one metastatic melanoma patient had a minor response during the study period. One other patient exhibited a mixed response.This study establishes the feasibility of large-scale expansion and safety of administering NK-92 cells as allogeneic cellular immunotherapy in advanced cancer patients and serves as a platform for future study of this novel natural killer (NK)-cell based therapy.

    View details for DOI 10.1080/14653240802301872

    View details for Web of Science ID 000259762000009

    View details for PubMedID 18836917

  • A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Newton Thompson, R., Gaw, A. F., Arai, S., Ortiz, R., Garber, A. M. 2007; 25 (6): 634-641

    Abstract

    One-year adjuvant trastuzumab (AT) therapy, with or without anthracyclines, increases disease-free and overall survival in early-stage HER2/neu-positive breast cancer. We sought to evaluate the cost effectiveness of these regimens, which are expensive and potentially toxic.We used a Markov health-state transition model to simulate three adjuvant therapy options for a cohort of 49-year-old women with HER2/neu-positive early-stage breast cancer: conventional chemotherapy without trastuzumab; anthracycline-based AT regimens used in the National Surgical Adjuvant Breast and Bowel Project B-31 and North Central Cancer Treatment Group N9831 trials; and the nonanthracycline AT regimen used in the Breast Cancer International Research group 006 trial. The base case used treatment efficacy measures reported in the randomized clinical trials of AT. We measured health outcomes in quality-adjusted life-years (QALYs) and costs in 2005 United States dollars (US dollars) and subjected results to probabilistic sensitivity analysis.In the base case, the anthracycline-based AT arm has an incremental cost-effectiveness ratio (ICER) of 39,982 dollars/QALY, whereas the nonanthracycline AT arm is more expensive and less effective; this result is insensitive to changes in recurrence rates, but if there is no benefit after 4 years, ICERs exceed 100,000 dollars/QALY for both AT arms. Results are moderately sensitive to variation in breast cancer survival rates and trastuzumab cost, and less sensitive to variations in cardiac toxicity.AT has an ICER comparable to those for other widely used interventions. Longer clinical follow-up is warranted to evaluate the long-term efficacy and toxicity of different AT regimens.

    View details for DOI 10.1200/JCO.2006.06.3081

    View details for Web of Science ID 000244384000006

    View details for PubMedID 17308268

  • Natural killer cells: can they be useful as adoptive immunotherapy for cancer? Expert Opin Biol Ther Arai S, Klingemann H-G 2005; 5: 163-172
  • Association of Foxp3 regulatory gene expression and graft-versus-host disease Blood Miura Y, Thoburn CJ, Bright EC, Phelps ML, Shin T, Matsui EC, Matsui WH, Arai S, Fuchs EJ, Vogelsang GB, Jones RJ, Hess AD 2004; 104: 2187-93
  • Poor outcome in steroid refractory GVHD with ATG treatment Biol Blood Marrow Transplant Arai S, Margolis J, Zahurak M, Anders V, Vogelsang GB 2002; 8: 155-60
  • von Willebrand factor-cleaving protease activity and proteolysis of von Willebrand factor in bone marrow transplant-associated thrombotic microangiopathy The Hematology Journal Arai S, Allan C, Streiff M, Hutchins GM, Vogelsang GB, Tsai HM 2001; 2: 292-299

Stanford Medicine Resources: