Robert J. Soiffer, MD
Professor of Medicine, Harvard Medical School
Office phone: 617-632-6256
Preferred contact method: email
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Stem cell/bone marrow transplantation, Leukemia, Lymphoma, Chronic lymphocytic leukemia
Area of ResearchImmunomodulation and Hematopoietic Stem Cell Transplantation
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
Dr. Soiffer graduated from New York University School of Medicine in 1983, and trained in internal medicine at Brigham and Women's Hospital, where he also was chief medical resident. He joined DFCI in 1988, after completing a medical oncology fellowship. He is currently chief of the Division of Hematologic Malignancies and codirector of the Adult Stem Cell Transplantation Program. He has served as vice president (2006), president (2007), and immediate past president (2008) of the American Society of Blood and Marrow Transplantation.
- Lee M. Nadler "Extra Mile" Award, DFCI, 2004
- Brian O'Dell Memorial Research Award, 2001
- Scholar for Clinical Research, Leukemia Society of America, 1999
- Baruj Benacerraf Fellow, DFCI, 1997
ResearchImmunomodulation and Hematopoietic Stem Cell Transplantation
The focus of our research for the past decade has been the development of treatment strategies to modulate the immune system of patients with cancer. These efforts are based on studies of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies. Although allogeneic transplantation can cure a proportion of these individuals, success is limited by transplant-related complications such as graft-versus-host disease (GVHD). It has long been recognized that T lymphocytes from the donor marrow play a pivotal role in the pathogenesis of GVHD.
In patients undergoing HSCT, depleting donor marrow T cells with an antibody to a T cell surface structure results in a dramatic decrease in the incidence of GVHD. This approach also eliminates the need for immune-suppressive medications. These agents can be toxic, causing organ damage and increasing susceptibility to infection. Recently we have explored strategies to selectively infuse CD8+ depleted lymphocytes in hopes of prompting graft-versus-leukemia (GVL) activity without producing GVHD. We validated this strategy in a randomized trial of CD8-depleted donor lymphocyte infusions after T cell-depleted allotransplantation, and are now conducting further trials on CD8 depletion.
While T cell depletion reduces GVHD, its effect on immune reactivity may lead to an increased risk of relapse of certain leukemias after transplantation. Preserving and restoring this GVL activity without compromising safety is a major thrust of our clinical and laboratory research. Working within the Cell Manipulation Core Facility, we have begun to identify specific T cell populations that may play a critical role in mediating antileukemia activity. We are exploring the role of regulatory T cells (Tregs) in the development of GVHD and GVL reactions, and have initiated a clinical trial to augment GVL reactivity using an antibody to CTLA4Ig, a molecule that controls immune reactions.
We are also investigating vaccination strategies for preventing relapse in allogeneic transplant patients. Previously, in collaboration with Dr. Glenn Dranoff, we found that vaccination with irradiated autologous tumor cells - genetically engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF) - induced histologic, cellular, and humoral evidence of autologous antitumor immunity in nontransplant patients. We are combining vaccine approaches with the administration of allogeneic donor stem cells in hopes of inducing a synergistic antileukemia effect.
- De Angelo DJ, Hochberg EP, Alyea EP, Longtine J, Lee S, Galinsky I, Parekkedon B, Ritz J, Antin JH, Stone RM, Soiffer, RJ. Extended follow-up of patients treated with imatinib mesylate (Gleevec) for CML relapse following allogeneic transplantation: durable cytogenetic remission and conversion to complete donor chimerism without GVHD. Clin Cancer Res 2004;10:5065-71.
- Alyea EP, Canning C, Neuberg D, Daley, H, Houde H, Giralt S, Champlin R, Atkinson K, Soiffer RJ. CD8+ cell depletion of donor lymphocyte infusions using cd8+ monoclonal antibody coated microparticles (CD8-HDM) after allogeneic hematopoietic stem cell transplantation: a pilot study. Bone Marrow Transplant 2004;34:123-8.
- Lee SJ, Zahrieh D, Agura E, MacMillan ML, Maziarz R, McCarthy PL, Ho VT, Cutler C, Alyea EP, Antin JH, Soiffer RJ. Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial. Blood 2004;104:1559-64.
- Ho VT, Kim HT, Li S, Hochberg EP, Cutler C, Lee SJ, Fisher DC, Milford E, Kao G, Daley H, Levin J, Ng A, Mauch P, Alyea EP, Antin JH, Soiffer RJ. Partial CD8+ T cell depletion of allogeneic peripheral blood stem cell transplantation is insufficient to prevent graft-versus-host disease. Bone Marrow Transplant 2004;34:987-94.
- Alyea EP, Kim HT, Ho VT, Cutler C, Gribben J, DeAngelo DA, Lee SJ, Windawi S, Ritz J, Stone RM, Antin JH, Soiffer RJ. Comparative outcome of non-myeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients greater than 50 years of age. Blood 2005;105:1810-4.
- Miklos DB, Kim HT, Miller KH, Guo L, Zorn E, Lee SJ, Hochberg EP, Wu CJ, Alyea EP, Cutler C, Ho VT, Soiffer RJ, Antin JH, Ritz J. Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Blood 2005;105:2973-8.
- Zorn E, Kim HT, Lee SJ, Floyd BH, Litsa D, Arumugarajah S, Bellucci R, Alyea EP, Antin JH, Soiffer RJ, Ritz J. Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood 2005;106:2903-11.
- Cutler C, Kim HT, Hochberg E, Ho VT, Alyea E, Lee SJ, Fisher DC, Miklos D, Levin J, Sonis S, Soiffer RJ, Antin JH. Sirolimus and tacrolimus without methotrexate as graft-versus-host disease prophylaxis after matched related donor peripheral blood stem cell transplantation. Biol Blood Marrow Transplant 2004;10:328-36.
- Antin JH, Kim HT, Cutler C, Ho V, Lee S, Miklos D, Hochberg E, Wu C, Alyea EP, Soiffer RJ. Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation. Blood 2003;102:1601-5.
- Soiffer R, Hodi FS, Haluska F, Jung K, Gillessen S, Singer S, Tanabe K, Duda R, Mentzer S, Jaklitsch M, Bueno R, Clift S, Hardy S, Neuberg D, Mulligan R, Webb I, Mihm M, Dranoff G. Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. J Clin Oncol 2003;21:3343-50.