Bio

Bio


Dr. Rezvani is an Assistant Professor of Medicine in the Division of Blood & Marrow Transplantation at Stanford University. His focus includes clinical care of patients undergoing allogeneic and autologous hematopoietic cell transplantation, as well as clinical research aimed at improving outcomes and reducing complications of these transplants. He has conducted both retrospective and prospective clinical research in support of these aims. He also teaches and serves as a research mentor for fellows in the Division of Blood & Marrow Transplant at Stanford.

Clinical Focus


  • Cancer > Blood and Marrow Transplant
  • Oncology

Academic Appointments


Honors & Awards


  • Member, Alpha Omega Alpha medical honor society (2001)

Boards, Advisory Committees, Professional Organizations


  • Member, Toxicity and Supportive Care Committee, Blood & Marrow Transplant Clinical Trials Network (BMT-CTN) (2015 - Present)
  • Editorial consultant, American College of Physicians PIER (2008 - Present)

Professional Education


  • Fellowship:Fred Hutchinson Cancer Research Center (2008) WA
  • Residency:Duke University Medical Center (2004) NC
  • Fellowship, Fred Hutchinson Cancer Research Center/University of Washington, Medical Oncology (2008)
  • Medical Education:Temple University Hospital (2001) PA
  • Residency, Duke University Medical Center, Internal Medicine (2004)
  • Board Certification: Oncology, American Board of Internal Medicine (2008)
  • M.D., Temple University, Medicine (2001)
  • B.A., Stanford University, Slavic Languages and Literature (1997)

Research & Scholarship

Current Research and Scholarly Interests


Clinical research in allogeneic hematopoietic cell transplantation

Clinical Trials


  • CD8+ Memory T-Cells as Consolidative Therapy After Donor Non-myeloablative Hematopoietic Cell Transplant in Treating Patients With Leukemia or Lymphoma 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).

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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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  • 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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  • 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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  • 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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  • Double Cord Versus Haploidentical (BMT CTN 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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  • Novel Approaches for Graft-versus-Host Disease Prevention Compared to Contemporary Controls (BMT CTN 1203) Not Recruiting

    Acute Graft-versus-Host-Disease (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). This study aims to determine if any of three new GVHD prophylaxis approaches improves the rate of GVHD and relapse free survival at one year after transplant compared to the current standard prophylaxis regimen.

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

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Publications

All Publications


  • Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors. Blood Kanate, A. S., Mussetti, A., Kharfan-Dabaja, M. A., Ahn, K. W., DiGilio, A., Beitinjaneh, A., Chhabra, S., Fenske, T. S., Freytes, C., Gale, R. P., Ganguly, S., Hertzberg, M., Klyuchnikov, E., Lazarus, H. M., Olsson, R., Perales, M., Rezvani, A., Riches, M., Saad, A., Slavin, S., Smith, S. M., Sureda, A., Yared, J., Ciurea, S., Armand, P., Salit, R., Bolaños-Meade, J., Hamadani, M. 2016; 127 (7): 938-947

    Abstract

    We evaluated 917 adult lymphoma patients who received haploidentical (n = 185) or HLA-matched unrelated donor (URD) transplantation either with (n = 241) or without antithymocyte globulin (ATG; n = 491) following reduced-intensity conditioning regimens. Haploidentical recipients received posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, whereas URD recipients received calcineurin inhibitor-based prophylaxis. Median follow-up of survivors was 3 years. The 100-day cumulative incidence of grade III-IV acute GVHD on univariate analysis was 8%, 12%, and 17% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .44). Corresponding 1-year rates of chronic GVHD on univariate analysis were 13%, 51%, and 33%, respectively (P < .001). On multivariate analysis, grade III-IV acute GVHD was higher in URD without ATG (P = .001), as well as URD with ATG (P = .01), relative to haploidentical transplants. Similarly, relative to haploidentical transplants, risk of chronic GVHD was higher in URD without ATG and URD with ATG (P < .0001). Cumulative incidence of relapse/progression at 3 years was 36%, 28%, and 36% in the haploidentical, URD without ATG, and URD with ATG groups, respectively (P = .07). Corresponding 3-year overall survival (OS) was 60%, 62%, and 50% in the 3 groups, respectively, with multivariate analysis showing no survival difference between URD without ATG (P = .21) or URD with ATG (P = .16), relative to haploidentical transplants. Multivariate analysis showed no difference between the 3 groups in terms of nonrelapse mortality (NRM), relapse/progression, and progression-free survival (PFS). These data suggest that reduced-intensity conditioning haploidentical transplantation with posttransplant cyclophosphamide does not compromise early survival outcomes compared with matched URD transplantation, and is associated with significantly reduced risk of chronic GVHD.

    View details for DOI 10.1182/blood-2015-09-671834

    View details for PubMedID 26670632

  • Microbiota Manipulation With Prebiotics and Probiotics in Patients Undergoing Stem Cell Transplantation. Current hematologic malignancy reports Andermann, T. M., Rezvani, A., Bhatt, A. S. 2016; 11 (1): 19-28

    Abstract

    Hematopoietic stem cell transplantation (HSCT) is a potentially life-saving therapy that often comes at the cost of complications such as graft-versus-host disease and post-transplant infections. With improved technology to understand the ecosystem of microorganisms (viruses, bacteria, fungi, and microeukaryotes) that make up the gut microbiota, there is increasing evidence of the microbiota's contribution to the development of post-transplant complications. Antibiotics have traditionally been the mainstay of microbiota-altering therapies available to physicians. Recently, interest is increasing in the use of prebiotics and probiotics to support the development and sustainability of a healthier microbiota. In this review, we will describe the evidence for the use of prebiotics and probiotics in combating microbiota dysbiosis and explore the ways in which they may be used in future research to potentially improve clinical outcomes and decrease rates of graft-versus-host disease (GVHD) and post-transplant infection.

    View details for DOI 10.1007/s11899-016-0302-9

    View details for PubMedID 26780719

  • Long-Term Sustained Disease Control in Patients With Mantle Cell Lymphoma With or Without Active Disease After Treatment With Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning CANCER Vaughn, J. E., Sorror, M. L., Storer, B. E., Chauncey, T. R., Pulsipher, M. A., Maziarz, R. T., Maris, M. B., Hari, P., Laport, G. G., Franke, G. N., Agura, E. D., Langston, A. A., Rezvani, A. R., Storb, R., Sandmaier, B. M., Maloney, D. G. 2015; 121 (20): 3709-3716

    Abstract

    Previously, early results were reported for allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning with 2 Gy of total body irradiation with or without fludarabine and/or rituximab in 33 patients with mantle cell lymphoma (MCL).This study examined the outcomes of 70 patients with MCL and included extended follow-up (median, 10 years) for the 33 initial patients. Grafts were obtained from human leukocyte antigen (HLA)-matched, related donors (47%), unrelated donors (41%), and HLA antigen-mismatched donors (11%).The 5-year incidence of nonrelapse mortality was 28%. The relapse rate was 26%. The 5-year rates of overall survival (OS) and progression-free survival (PFS) were 55% and 46%, respectively. The 10-year rates of OS and PFS were 44% and 41%, respectively. Eighty percent of surviving patients were off immunosuppression at the last follow-up. The presence of relapsed or refractory disease at the time of HCT predicted a higher rate of relapse (hazard ratio [HR], 2.94; P = .05). Despite this, OS rates at 5 (51% vs 58%) and 10 years (43% vs 45%) were comparable between those with relapsed/refractory disease and those undergoing transplantation with partial or complete remission. A high-risk cytomegalovirus (CMV) status was the only independent predictor of worse OS (HR, 2.32; P = .02). A high-risk CMV status and a low CD3 dose predicted PFS (HR, 2.22; P = .03).Nonmyeloablative allogeneic HCT provides a long-term survival benefit for patients with relapsed MCL, including those with refractory disease or multiple relapses. Cancer 2015;121:3709-3716. © 2015 American Cancer Society.

    View details for DOI 10.1002/cncr.29498

    View details for Web of Science ID 000363262700020

    View details for PubMedID 26207349

  • Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning BONE MARROW TRANSPLANTATION Rezvani, A. R., Kanate, A. S., Efron, B., Chhabra, S., Kohrt, H. E., Shizuru, J. A., Laport, G. G., Miklos, D. B., Benjamin, J. E., JOHNSTON, L. J., Arai, S., Weng, W., Negrin, R. S., Strober, S., Lowsky, R. 2015; 50 (10): 1286-1292

    Abstract

    We describe 47 patients with lymphoma and failed prior autologous hematopoietic cell transplantation (HCT) who received TLI-ATG (anti-thymocyte globulin) conditioning followed by allogeneic HCT. Thirty-two patients had non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma (n=19), T-cell NHL (n=6), mantle cell lymphoma (n=4) or other B-cell subtypes (n=3)), and 15 had Hodgkin lymphoma. The median follow-up was 4.9 (range, 2.1-11.9) years. The cumulative incidence of grade II-IV acute GvHD at day +100 was 12%, and the cumulative incidence of extensive chronic GvHD at 1 year was 36%. The 3-year cumulative incidences of overall survival (OS), PFS and non-relapse mortality (NRM) were 81%, 44% and 7%, respectively. Fifteen patients died (relapse, n=10; NRM, n=5). Among the 25 patients with relapse after allogeneic HCT, 11 (44%) achieved durable (>1 year) CRs following donor lymphocyte infusion or chemoradiotherapy. The majority of surviving patients (75%; n=24) were able to discontinue all immunosuppression. For patients with relapsed lymphoma after autologous HCT, allogeneic HCT using TLI-ATG conditioning is a well-tolerated, predominantly outpatient therapy with low NRM (7% at 3 years), a low incidence of GvHD, durable disease control and excellent OS (81% at 3 years).

    View details for DOI 10.1038/bmt.2015.149

    View details for Web of Science ID 000362497400004

  • Long-term outcomes of patients with persistent indolent b cell malignancies undergoing nonmyeloablative allogeneic transplantation. Biology of blood and marrow transplantation Cassaday, R. D., Storer, B. E., Sorror, M. L., Sandmaier, B. M., Guthrie, K. A., Maloney, D. G., Rajendran, J. G., Pagel, J. M., Flowers, M. E., Green, D. J., Rezvani, A. R., Storb, R. F., Press, O. W., Gopal, A. K. 2015; 21 (2): 281-287

    Abstract

    Relapse is least common in patients with indolent B cell (iB) malignancies (ie, iB non-Hodgkin lymphoma [NHL]) who undergo nonmyeloablative allogeneic transplantation (NMAT) in complete remission (CR). However, for the many patients unable to achieve this state, outcomes are poorly described and methods to improve results are unknown. We sought to describe the long-term follow-up and predictive factors for these poor-risk patients unable to achieve CR before NMAT. We identified and evaluated patients with iB-NHL including chronic lymphocytic leukemia treated with fludarabine/total body irradiation-based NMAT that had evidence of persistent disease before NMAT. From December 1998 to April 2009, 89 patients were identified, most commonly with small/chronic lymphocytic lymphoma (n = 62) and follicular lymphoma (n = 24). Pretransplant anti-CD20 radioimmunotherapy (RIT) using standard yttrium-90-ibritumomab tiuxetan was administered to 18 patients (20%) who more frequently had chemoresistant disease (81% versus 39%, P = .003), disease bulk > 5 cm (61% versus 15%, P < .001), thrombocytopenia < 25k/μL (33% versus 7%, P = .002), and Hematopoietic Cell Transplant Comorbidity Index scores ≥ 3 (72% versus 37%, P = .006). After adjusting for these imbalances, RIT-treated patients had improved rates of progression-free survival (PFS) (hazard ratio [HR] = .4; 95% confidence interval [CI], .2 to .9, P = .02) and overall survival (OS) (HR = .3; 95% CI, .1 to .8, P = .008) compared with the non-RIT group. The 3-year adjusted estimates of PFS and OS for the RIT and non-RIT groups were 71% and 87% versus 44% and 59%, respectively. The use of RIT was the only factor independently associated with improved PFS and OS. Rates of nonrelapse mortality and graft-versus-host disease (GVHD) were similar between the 2 groups, although over 70% of patients developed clinically significant acute or chronic GVHD. In conclusion, despite relatively high rates of GVHD, patients with persistent iB-NHL can derive durable benefit from NMAT.

    View details for DOI 10.1016/j.bbmt.2014.10.024

    View details for PubMedID 25445025

  • Impact of donor age on outcome after allogeneic hematopoietic cell transplantation. Biology of blood and marrow transplantation Rezvani, A. R., Storer, B. E., Guthrie, K. A., Schoch, H. G., Maloney, D. G., Sandmaier, B. M., Storb, R. 2015; 21 (1): 105-112

    Abstract

    As older patients are eligible for allogeneic hematopoietic cell transplantation (HCT), older siblings are increasingly proposed as donors. We studied the impact of donor age on the tempo of hematopoietic engraftment and donor chimerism, acute and chronic graft-versus-host disease (GVHD), and nonrelapse mortality (NRM) among 1174 consecutive patients undergoing myeloablative and 367 patients undergoing nonmyeloablative HCT from HLA-matched related or unrelated donors with granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell allografts. Sustained engraftment rates were 97% and 98% in patients undergoing myeloablative and nonmyeloablative conditioning, respectively, for grafts from donors < 60 years old (younger; n = 1416) and 98% and 100%, respectively, for those from donors ≥60 years old (older; n = 125). No significant differences were seen in the tempo of neutrophil and platelet recoveries and donor chimerism except for an average 1.3-day delay in neutrophil recovery among myeloablative patients with older donors (P = .04). CD34(+) cell dose had an independent effect on the tempo of engraftment. Aged stem cells did not convey an increased risk of donor-derived clonal disorders after HCT. Myeloablative and nonmyeloablative recipients with older sibling donors had significantly less grade II to IV acute GVHD than recipients with grafts from younger unrelated donors. Rates of grade III and IV acute GVHD, chronic GVHD, and NRM for recipients with older donors were not significantly different from recipients with younger donors. In conclusion, grafts from donors ≥60 years old do not adversely affect outcomes of allogeneic HCT compared with grafts from younger donors.

    View details for DOI 10.1016/j.bbmt.2014.09.021

    View details for PubMedID 25278458

  • Allogeneic hematopoietic cell transplantation for indolent non-Hodgkin lymphoma: indications and outcomes CURRENT OPINION IN HEMATOLOGY Rezvani, A. R., Sandmaier, B. M. 2013; 20 (6): 509-514

    Abstract

    Allogeneic hematopoietic cell transplantation (HCT) can potentially cure indolent non-Hodgkin lymphoma (NHL). However, the optimal timing and indications remain unclear. Here, we review recent published reports on the subject and summarize our approach.Recent prospective clinical trials of allogeneic HCT in indolent NHL are marked by substantial variation in eligibility criteria, patient populations, and transplant approach. Nonetheless, several common themes are apparent. Indolent NHL is highly susceptible to immunologic graft-versus-lymphoma effects and relapse rates after allogeneic HCT are uniformly low. Allogeneic HCT early in the disease course produces the highest overall and progression-free survival, but also increases patient exposure to potential transplant-related complications such as chronic graft-versus-host disease. In contrast, allogeneic HCT can be reserved as a 'last resort' for patients who are refractory to conventional chemotherapy, delaying their exposure to graft-versus-host disease and other transplant-associated risks. No trials have directly addressed the optimal timing of allogeneic HCT in indolent NHL nor prospectively compared different transplant approaches.Excellent outcomes have been reported with allogeneic HCT for indolent NHL, both early and late in the disease course. The optimal timing of allogeneic HCT is unknown and depends heavily on patient preferences.

    View details for DOI 10.1097/MOH.0b013e328365a151

    View details for Web of Science ID 000326746100004

    View details for PubMedID 24104411

  • Inducible costimulator (ICOS) up-regulation on activated T cells in chronic graft-versus-host disease after dog leukocyte antigen-nonidentical hematopoietic cell transplantation: a potential therapeutic target. Transplantation Sato, M., Storb, R., Loretz, C., Stone, D., Mielcarek, M., Sale, G. E., Rezvani, A. R., Graves, S. S. 2013; 96 (1): 34-41

    Abstract

    Inducible costimulator (ICOS), a member of the CD28 family of costimulatory molecules, is induced on CD4 and CD8 T cells after their activation. ICOS functions as an essential immune regulator and ICOS blockade is a potential approach to immune modulation in allogeneic transplantation. Here, we describe the expression profile of ICOS in dogs and determine whether ICOS expression is up-regulated during chronic graft-versus-host disease (GVHD) and host-versus-graft reactions in the canine hematopoietic cell transplantation model.Monoclonal antibodies (mAbs) against cell surface-expressed ICOS were produced and tested in vitro for suppression of canine mixed leukocyte reactions (MLR). Expression of ICOS on CD3 cells was evaluated by flow cytometry using peripheral blood, lymph nodes, and splenocytes obtained from dogs undergoing graft-versus-host and host-versus-graft reactions.Canine ICOS was expressed in an inducible pattern on T cells activated by concanavalin A, anti-CD3 mAb in combination with anti-CD28 mAb, and alloantigen stimulation. Immunosuppressive effects of ICOS blockade were observed in MLR using peripheral blood mononuclear cells from dog leukocyte antigen-nonidentical dogs. Immunosuppressive effects of ICOS blockade were observed in MLR when anti-ICOS was combined with suboptimal concentrations of cytotoxic T-lymphocyte antigen 4-Ig or cyclosporine. ICOS expression was significantly up-regulated on T cells in dogs undergoing graft rejection or chronic GVHD after allogeneic hematopoietic cell transplantation.These studies suggest that ICOS plays a role in graft rejection and GVHD in an outbred animal model, and ICOS blockade may be an approach to prevention and treatment of chronic GVHD.

    View details for DOI 10.1097/TP.0b013e318295c025

    View details for PubMedID 23694952

  • Cyclophosphamide followed by Intravenous Targeted Busulfan for Allogeneic Hematopoietic Cell Transplantation: Pharmacokinetics and Clinical Outcomes BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Rezvani, A. R., McCune, J. S., Storer, B. E., Batchelder, A., Kida, A., Deeg, H. J., McDonald, G. B. 2013; 19 (7): 1033-1039

    Abstract

    Targeted busulfan ((T)BU) and cyclophosphamide (CY) for allogeneic hematopoietic cell transplantation carries a high risk of sinusoidal obstruction syndrome (SOS) in patients undergoing transplantation for myelofibrosis. We tested the hypothesis that reversing the sequence of administration (from (T)BU/CY to CY/(T)BU) would reduce SOS and day +100 nonrelapse mortality. We enrolled 51 patients with myelofibrosis (n = 20), acute myelogenous leukemia (n = 20), or myelodysplastic syndrome (n = 11) in a prospective trial of CY/(T)BU conditioning for allogeneic hematopoietic cell transplantation. CY 60 mg/kg/day i.v. for 2 days was followed by daily i.v. BU for 4 days, targeted to a concentration at steady state (Css) of 800-900 ng/mL. Compared with (T)BU/CY-conditioned patients, CY/(T)BU-conditioned patients had greater exposure to CY (P < .0001) and less exposure to 4-hydroxycyclophosphamide (P < .0001). Clinical outcomes were compared between cases and controls (n = 271) conditioned with (T)BU/CY for the same indications. In patients with myelofibrosis, CY/(T)BU conditioning was associated with a significantly reduced incidence of SOS (0% versus 30% after (T)BU/CY; P = .006), whereas the incidence of SOS was low in both cohorts with acute myelogenous leukemia/myelodysplastic syndrome. Day +100 mortality was significantly lower in the CY/(T)BU cohort (2% versus 13%; P = .01). CY/(T)BU conditioning had a marked affect on the pharmacokinetics of CY and was associated with significantly lower incidence of SOS and day +100 mortality, suggesting that CY/(T)BU is superior to (T)BU/CY as conditioning for patients with myelofibrosis.

    View details for DOI 10.1016/j.bbmt.2013.04.005

    View details for Web of Science ID 000321093500008

    View details for PubMedID 23583825

  • Prevention of graft-vs.-host disease EXPERT OPINION ON PHARMACOTHERAPY Rezvani, A. R., Storb, R. F. 2012; 13 (12): 1737-1750

    Abstract

    Allogeneic hematopoietic cell transplantation (HCT) is a curative treatment for many malignant and non-malignant hematologic disorders. However, graft-vs.-host disease (GVHD) remains a major complication of allogeneic HCT and limits the success of this approach.This paper reviews recent developments in the prevention of acute and chronic GVHD. In the setting of acute GVHD prevention, recent trials of T-cell depletion using Fresenius-ATG are reviewed, as well as studies testing total lymphoid irradiation, mesenchymal stromal cells, rituximab, statins, sirolimus and other investigational agents. In the setting of chronic GVHD, results with Fresenius-ATG are reviewed, as well as B-cell depletion with rituximab, and the potential role of the B-cell regulatory cytokine BAFF in chronic GVHD is also discussed. Finally, the emerging role of resident skin and gut bacterial flora-the so-called microbiome-in the pathogenesis of GVHD is covered.Current methods of acute GVHD prevention are highly successful, and a number of investigational approaches promise to further reduce the risk of this complication. By contrast, chronic GVHD is more poorly understood and more difficult to prevent. Future studies are required to delineate the roles of these approaches and to abrogate GVHD without sacrificing the beneficial immunologic graft-vs.-tumor effect.

    View details for DOI 10.1517/14656566.2012.703652

    View details for Web of Science ID 000306524600007

    View details for PubMedID 22770714

  • The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation BLOOD Scott, B. L., Gooley, T. A., Sorror, M. L., Rezvani, A. R., Linenberger, M. L., Grim, J., Sandmaier, B. M., Myerson, D., Chauncey, T. R., Storb, R., Buxhofer-Ausch, V., Radich, J. P., Appelbaum, F. R., Deeg, H. J. 2012; 119 (11): 2657-2664

    Abstract

    Studies by the International Working Group showed that the prognosis of myelofibrosis patients is predicted by the Dynamic International Prognostic Scoring System (DIPSS) risk categorization, which includes patient age, constitutional symptoms, hemoglobin, leukocyte count, and circulating blasts. We evaluated the prognostic usefulness of the DIPSS in 170 patients with myelofibrosis, 12 to 78 years of age (median, 51.5 years of age), who received hematopoietic cell transplantation (HCT) between 1990 and 2009 from related (n = 86) or unrelated donors (n = 84). By DIPSS, 21 patients had low-risk disease, 48 had intermediate-1, 50 had intermediate-2, and 51 had high-risk disease. Five-year incidence of relapse, relapse-free survival, overall survival, and nonrelapse mortality for all patients were 10%, 57%, 57%, and 34%, respectively. Among patients with DIPSS high-risk disease, the hazard ratio for post-HCT mortality was 4.11 (95% CI, 1.44-11.78; P = .008), and for nonrelapse mortality was 3.41 (95% CI, 1.15-10.09; P = .03) compared with low-risk patients. After a median follow-up of 5.9 years, the median survivals have not been reached for DIPSS risk groups low and intermediate-1, and were 7 and 2.5 years for intermediate-2 and high-risk patients, respectively. Thus, HCT was curative for a large proportion of patients with myelofibrosis, and post-HCT success was dependent on pre-HCT DIPSS classification.

    View details for DOI 10.1182/blood-2011-08-372904

    View details for Web of Science ID 000301941700035

    View details for PubMedID 22234678

  • Accurate Targeting of Daily Intravenous Busulfan with 8-Hour Blood Sampling in Hospitalized Adult Hematopoietic Cell Transplant Recipients BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Yeh, R. F., Pawlikowski, M. A., Blough, D. K., McDonald, G. B., O'Donnell, P. V., Rezvani, A., Deeg, H. J., McCune, J. S. 2012; 18 (2): 265-272

    Abstract

    Daily intravenous (i.v.) busulfan is increasingly being used in hematopoietic cell transplantation (HCT) conditioning regimens. Intravenous busulfan doses administered at the traditional frequency of every 6 hours can be targeted ((T)Bu) to a patient-specific concentration at steady state (C(ss)) using therapeutic drug monitoring (TDM). In this report, we describe our experiences with TDM of daily i.v. busulfan in an adult population, with the specific aims of (1) evaluating covariates associated with busulfan clearance, and (2) assessing the feasibility of TDM for outpatient administration of daily (T)Bu with pharmacokinetic sampling over 6 hours. A retrospective pharmacokinetic analysis was conducted in 87 adults receiving daily (T)Bu as part of cyclophosphamide followed by (T)BU (CY/(T)BU), fludarabine monophosphate (fludarabine) followed by (T)BU, or (T)BU concurrent with fludarabine conditioning. The desired C(ss) was achieved in 85% of patients receiving daily i.v. busulfan. Busulfan clearance was not associated with sex or age, but was associated with the day of dosing and conditioning regimen (P = .0016). In patients receiving CY/(T)BU, no differences in clearance were found between dosing days (P > .36); however, clearance decreased significantly in patients receiving fludarabine-based regimens (P = .0016). Busulfan clearance and C(ss) estimates from pharmacokinetic sampling over 8, 11, or 24 hours were comparable (P > .4). However, pharmacokinetic modeling of individual patient concentration-time data over 6 hours could not reliably estimate busulfan clearance or C(ss).

    View details for DOI 10.1016/j.bbmt.2011.06.013

    View details for Web of Science ID 000299398500015

    View details for PubMedID 21736869

  • Decreased Serum Albumin as a Biomarker for Severe Acute Graft-versus-Host Disease after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Rezvani, A. R., Storer, B. E., Storb, R. F., Mielcarek, M., Maloney, D. G., Sandmaier, B. M., Martin, P. J., McDonald, G. B. 2011; 17 (11): 1594-1601

    Abstract

    Biomarkers capable of predicting the onset and severity of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HCT) would enable preemptive and risk-stratified therapy. Severe aGVHD leads to gastrointestinal protein loss, resulting in hypoalbuminemia. We hypothesized that decreases in serum albumin at onset of aGVHD would predict the risk of progression to severe aGVHD. We identified 401 patients who developed aGVHD grades II-IV after reduced-intensity allogeneic HCT and reviewed all available serum albumin values from 30 days before HCT to 45 days after initiation of treatment for aGVHD. A ≥0.5 g/dL decrease in serum albumin concentration from pretransplantation baseline to the onset of treatment for aGVHD predicted the subsequent development of grade III/IV aGVHD (versus grade II aGVHD) with a sensitivity of 69% and a specificity of 73%. Overall mortality at 6 months after initiation of aGVHD treatment was 36% versus 17% for patients with and without ≥0.5 g/dL decreases in serum albumin, respectively (P = .0009). We conclude that change in serum albumin concentration from baseline to initiation of aGVHD treatment is an inexpensive, readily available, and predictive biomarker of GVHD severity and mortality after reduced-intensity allogeneic HCT.

    View details for DOI 10.1016/j.bbmt.2011.07.021

    View details for Web of Science ID 000296829000006

    View details for PubMedID 21806949

  • Rituximab resistance BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY Rezvani, A. R., Maloney, D. G. 2011; 24 (2): 203-216

    Abstract

    Rituximab has become a ubiquitous component of treatment regimens for follicular non-Hodgkin lymphoma. Despite widespread clinical use, the mechanisms by which tumor cells resist rituximab-mediated destruction remain unclear. Rituximab relies in part on immune effector mechanisms for its antitumor effect, and thus resistance may be mediated not only by intrinsic tumor-cell alterations but also by the host immunological environment. In this article, we explore the mechanisms of action of rituximab, the incidence of rituximab resistance, and potential mechanisms of resistance. Finally, we discuss novel approaches to modulate the antibody, the tumor cell, and the host immunologic environment to overcome rituximab resistance. Further research into the mechanisms of rituximab resistance will be essential to improving the efficacy of anti-CD20 therapy in NHL, and may also pay dividends in the optimization of monoclonal antibody therapy across a wide range of diseases.

    View details for DOI 10.1016/j.beha.2011.02.009

    View details for Web of Science ID 000292355200010

    View details for PubMedID 21658619

  • Allogeneic hematopoietic cell transplantation: the state of the art EXPERT REVIEW OF HEMATOLOGY Gyurkocza, B., Rezvani, A., Storb, R. F. 2010; 3 (3): 285-299

    Abstract

    Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative procedure for a variety of hematologic malignancies. The field has evolved substantially over the past decade, with advances in patient and donor selection, stem cell sources, supportive care, prevention of complications and reduced-toxicity preparative regimens. As a result, the indications for HCT and the pool of eligible patients have expanded significantly. In this article, we provide an overview of the major aspects of allogeneic HCT, and focus specifically on areas of active research and on novel approaches to challenges in the field. Specifically, we will discuss approaches to reduce the toxicity of the preparative regimen, with the goal of increasing the safety and applicability of HCT. The availability of suitable donors may be an obstacle to wider application of HCT. We review three major approaches to broadening the donor pool: the use of HLA-mismatched unrelated donors, umbilical cord blood and HLA-haploidentical family donors. Graft-versus-host disease remains a major cause of morbidity and mortality after HCT. We review recent advances in the understanding of this phenomenon, and novel prophylactic and therapeutic approaches that hold the promise of further improving the safety of the procedure. We conclude with a speculative outline of the next 5 years of research in the field of HCT.

    View details for DOI 10.1586/EHM.10.21

    View details for Web of Science ID 000284801600012

    View details for PubMedID 20871781

  • Treatment Change as a Predictor of Outcome among Patients with Classic Chronic Graft-versus-Host Disease BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Flowers, M. E., Storer, B., Carpenter, P., Rezvoni, A. R., Vigorito, A. C., Campregher, P. V., Moravec, C., Kiem, H., Fero, M., Georges, G., Warren, E., Lee, S., Sanders, J. E., Appelbaum, F., Martin, P. J. 2008; 14 (12): 1380-1384

    Abstract

    We analyzed outcomes for 668 patients who had systemic treatment for chronic graft-versus-host disease (cGVHD) to assess the utility of early treatment change for exacerbation of cGVHD as a surrogate for survival endpoints in clinical trials. Fifty-six percent of patients had treatment change within 2 years after diagnosis of cGVHD. The median onset of treatment change was 4.4 months (range: 0.3-50 months). The cumulative incidence of nonrelapse mortality (NRM) at 2 years was 16%, and overall survival (OS) at 2 years was 74%. In time-dependent Cox models, treatment change was associated with an increase in risk of NRM (hazard ratio, 2.53; 95% confidence interval, 1.7-3.7; P < .0001). The hazard ratio was attenuated by 6% per month of delay in treatment change. Our results confirm that exacerbation of cGVHD is associated with an increased risk of NRM and with decreased OS, but the strength of this association is not large enough to allow the use of early exacerbation as a surrogate for survival endpoints in clinical trials. Other measures of clinical benefit, such as response, will need to be developed as endpoints in phase II trials for patients with cGVHD.

    View details for DOI 10.1016/j.bbmt.2008.09.017

    View details for Web of Science ID 000261754600008

    View details for PubMedID 19041060

  • Non-myeloablative allogeneic haematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: a multicentre experience BRITISH JOURNAL OF HAEMATOLOGY Rezvani, A. R., Norasetthada, L., Gooley, T., Sorror, M., Bouvier, M. E., Sahebi, F., Agura, E., Chauncey, T., Maziarz, R. T., Maris, M., Shizuru, J., Bruno, B., Bredeson, C., Lange, T., Yeager, A., Sandmaier, B. M., Storb, R. F., Maloney, D. G. 2008; 143 (3): 395-403

    Abstract

    Patients with relapsed diffuse large B-cell lymphoma (DLBCL) who have failed or are ineligible for autologous haematopoietic cell transplantation (HCT) have a poor prognosis. We examined the outcomes of non-myeloablative allogeneic HCT in this setting. Thirty-one patients with DLBCL and one patient with Burkitt lymphoma received allogeneic HCT following 2 Gy total body irradiation with or without fludarabine. Median age was 52 years. Twenty-four patients (75%) had undergone prior autologous HCT. Disease status at HCT was complete response (14/32, 44%), partial response (9/32, 28%), or refractory (9/32, 28%). Cumulative incidences of acute graft-versus-host disease (GVHD) grades II-IV, grades III-IV, and chronic GVHD were 53%, 19%, and 47% respectively. With a median follow-up of 45 months, 3-year estimated overall (OS) and progression-free survival (PFS) was 45% and 35% respectively. Three-year cumulative incidences of relapse and non-relapse mortality were 41% and 25% respectively. In multivariate models, chemosensitive disease and receipt of >or=4 lines of treatment before HCT were associated with better OS. Patients with chemosensitive disease had 3-year OS and PFS of 56% and 43% respectively. Non-myeloablative allogeneic HCT can produce long-term disease-free survival in patients with chemosensitive relapsed DLBCL who have failed or are ineligible for autologous HCT.

    View details for DOI 10.1111/j.1365-2141.2008.07365.x

    View details for Web of Science ID 000260117300012

    View details for PubMedID 18759762

  • Separation of graft-vs.-tumor effects from graft-vs.-host disease in allogeneic hematopoietic cell transplantation JOURNAL OF AUTOIMMUNITY Rezvani, A. R., Storb, R. F. 2008; 30 (3): 172-179

    Abstract

    Allogeneic hematopoietic cell transplantation (HCT) is an increasingly widely used treatment modality in hematological malignancies. Alloreactivity mediated by donor T cells (and, in some settings, by donor natural killer cells) can produce durable immunologic control or eradication of residual malignancy after allogeneic HCT. However, graft-vs.-tumor (GVT) effects are variably effective and are often accompanied by deleterious alloreactivity against normal host tissue, manifesting as graft-vs.-host disease (GVHD). A major focus of current research in HCT is the separation of beneficial GVT effects from GVHD. Here we review a number of approaches currently under investigation to specifically augment GVT effects, including the identification of minor histocompatibility antigens (mHA), adoptive immunotherapy with tumor-specific or mHA-specific cytotoxic T lymphocytes, vaccination of the donor or recipient to stimulate tumor-specific immunity, and adoptive transfer of natural killer cells. In addition, we review strategies being investigated to specifically suppress GVHD while sparing GVT, including the manipulation and infusion of regulatory T cells, the use of novel pharmacologic and biologic agents, and the use of mesenchymal stem cells. Ultimately, advances in separation of GVT from GVHD will further enhance the potential of allogeneic HCT as a curative treatment for hematological malignancies.

    View details for DOI 10.1016/j.jaut.2007.12.002

    View details for Web of Science ID 000253769900010

    View details for PubMedID 18242060

  • Using allogeneic stem cell/T-cell grafts to cure hematologic malignancies EXPERT OPINION ON BIOLOGICAL THERAPY Rezvani, A. R., Storb, R. 2008; 8 (2): 161-179

    Abstract

    Background: Allogeneic stem cell and T-cell-based therapies are widely used in the treatment of hematologic malignancies and can treat or cure otherwise refractory disease. However, in spite of major advances in the understanding and practice of allogeneic hematopoietic cell transplantation (HCT), several important challenges remain. Objective: Here the authors review the use of allogeneic HCT and T-cell-based therapy, with the goal of providing an overview of the uses and limitations of this approach as well as a survey of areas of active research. Methods: The authors review and summarize recent publications and expert opinions in the field of allogeneic HCT, along with a brief historical perspective, with a focus on challenges and recent advances in the field. Results/conclusion: Present areas of research include efforts to expand the donor pool through the use of umbilical cord blood and human leukocyte antigen-haploidentical donors, the use of reduced-intensity conditioning regimens, which allow treatment of previously ineligible patients, enhancement of immune reconstitution after transplantation, more effective prevention and treatment of acute and chronic graft-versus-host disease, and the augmentation of the immunologic graft-versus-tumor response and its uncoupling from deleterious graft-versus-host alloreactivity.

    View details for DOI 10.1517/14712598.8.2.161

    View details for Web of Science ID 000252878300004

    View details for PubMedID 18194073

  • Nonmyeloablative allogeneic hematopoietic cell transplantation in relapsed, refractory, and transformed indolent non-Hodgkin's lymphoma JOURNAL OF CLINICAL ONCOLOGY Rezvani, A. R., Storer, B., Maris, M., Sorror, M. L., Agura, E., Maziarz, R. T., Wade, J. C., Chauncey, T., Forman, S. J., Lange, T., Shizuru, J., Langston, A., Pulsipher, M. A., Sandmaier, B. M., Storb, R., Maloney, D. G. 2008; 26 (2): 211-217

    Abstract

    Few effective treatment options exist for chemotherapy-refractory indolent or transformed non-Hodgkin's lymphoma (NHL). We examined the outcome of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in this setting.Sixty-two patients with indolent or transformed NHL were treated with allogeneic HCT from related (n = 34) or unrelated (n = 28) donors after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Nine unrelated donors were mismatched for >/= one HLA antigen. Sixteen patients had histologic transformation before HCT. Twenty patients (32%) had progressive disease after previous high-dose therapy with autologous HCT. Median age was 54 years, and patients had received a median of six lines of treatment before HCT. Median follow-up time after HCT was 36.6 months.At 3 years, the estimated overall survival (OS) and progression-free survival (PFS) rates were 52% and 43%, respectively, for patients with indolent disease, and 18% and 21%, respectively, for patients with transformed disease. Patients with indolent disease and related donors (n = 26) had 3-year estimated OS and PFS rates of 67% and 54%, respectively. The incidences of grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 and 4 acute GVHD, and extensive chronic GVHD were 63%, 18%, and 47%, respectively. Among survivors, the median Karnofsky performance status at last follow-up was 85%.Nonmyeloablative allogeneic HCT can produce durable disease-free survival in patients with relapsed or refractory indolent NHL, even in this relatively elderly and heavily pretreated cohort. Outcomes were particularly good in patients with untransformed disease and related donors, whereas patients with transformed disease did poorly. Long-term survivors reported good overall functional status.

    View details for DOI 10.1200/JCO.2007.11.5477

    View details for Web of Science ID 000254177100010

    View details for PubMedID 18056679