Bio

Clinical Focus


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

Academic Appointments


Professional Education


  • Internship:UCSF Medical Center (1993) CA
  • Residency:UCSF Medical Center (1994) CA
  • Fellowship:Stanford University Medical Center (1997) CA
  • Medical Education:Stanford University School of Medicine (1992) CA

Research & Scholarship

Current Research and Scholarly Interests


The research interests are to understand the cellular and molecular basis of resistance to engraftment of transplanted allogeneic bone marrow (BM) cells and to understand the way in which BM grafts modify immune responses. This research complements our interest in clinical BM transplantation and aspects of these studies are aimed at solving some of the major problems of BM transplantation which include graft-vs-host disease and BM engraftment failure. Conventional BM transplantation involves the transfer of heterogeneous populations of cells composed of rare hematopoietic stem cells (HSCs) and differentiated blood cell types. To study these issues our approach has been to transplant phenotypically purified cells under defined conditions. The specific projects in my laboratory include:

1) Identification of the cells and molecules responsible for resistance to engraftment of purified allogeneic HSCs. We and others have shown that cells with NK determinants constitute a significant barrier to allogeneic HSC engraftment, and that transplanted whole BM contains a population that facilitates engraftment. In these experiments our approach to identify the cell population(s) and mechanism by which HSC engraftment is resisted is to use recipient mice from strains that lack defined immune functions. We are studying the cells in BM and spleen that are bound and/or depleted by a-ASGMI, and in this way identify the candidate barrier populations.

2) Use of transplants of purified HSCs to induce tolerance to allo- and autoantigens, and study of the mechanisms by which such tolerance is induced. We continue to develop preclinical models for organ tolerance induction and treatment of autoimmune disease by using cell specific therapy. One goal is to decrease the morbidity of the recipient preparative regimen and to determine the lowest level of chimerism needed to induce immune tolerance. We propose to test donor/host strain combinations most relevant to human disease, including minor mismatched and haploidentical grafts.

3) Identification of the cells and molecules that confer graft vs leukemia/lymphoma (GVL) effects. We have developed a model of B cell lymphoma relapse after HSC transplant. To date our studies show that while purified allogeneic HSCs have no GVL activity, a population of BM cells that express CD3 and CD8 have significant GVL activity, and do not cause GVHD at the cell doses administered.

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

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  • 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.

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  • 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.

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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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  • 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.

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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 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.

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  • 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.

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  • Haploid Allogeneic Transplant Using the CliniMACS System Not Recruiting

    To assess the proportion of patients with donor neutrophil engraftment on or before day 30 post 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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  • Phase II Poor Risk Diffuse Large B-cell Lymphoma (DLBCL) of Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) Followed by Matched Allogeneic Hematopoietic Transplantation as Consolidation to Autologous Hematopoietic Cell Transplantation (AHCT) Not Recruiting

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

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

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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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.

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  • 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.

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  • 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.

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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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  • 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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  • 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.

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  • 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.

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  • Combined Blood Stem Cell and Human Leukocyte Antigen (HLA) Haplotype Match Living Donor Kidney Transplantation Recruiting

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

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  • 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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  • 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.

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

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

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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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.

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  • 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.

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  • 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.

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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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  • 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.

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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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  • 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.

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

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

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

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

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

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Teaching

2013-14 Courses


Postdoctoral Advisees


Graduate and Fellowship Programs


Publications

Journal Articles


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

    Abstract

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

    View details for Web of Science ID 000175933100002

    View details for PubMedID 12023614

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