DF/HCC Program Affiliation

Cancer Immunology

Research Abstract

Allogeneic bone marrow transplantation is curative for some patients with hematologic malignancies. Evidence suggests that the success of transplant is related not only to high doses of chemotherapy and radiation but also to the donor's immune system and whether it mediates an antileukemia effect -- termed the graft-versus-leukemia (GVL) effect.

Our group is currently exploring clinical methods to induce the GVL effect after bone marrow transplant. We have demonstrated that by infusing selected donor CD4+ lymphocytes, we can maintain the anti-leukemia activity while reducing the incidence of graft-versus-host disease. We are now conducting studies using donor dendritic cells and donor lymphocyte infusion (DLI) in an attempt to improve the response to DLI.

We are also exploring non-myeloablative transplantation strategies to establish a platform for adoptive immunotherapy. These 'mini' transplants allow allogeneic transplantation to be performed with much less toxicity -- permitting patients of more advanced age or with other medical conditons to undergo transplantation. In addition, we are conducting studies focused on augmenting GVL after 'mini'-transplantation.

Publications

• Lee SJ, Kim HT, Ho VT, Cutler C, Alyea EP, Soiffer RJ, Antin JH.Quality of life associated with acute and chronic graft-versus-host disease.Bone Marrow Transplant 2006 Jul 3.
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• Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D, Klickstein LB, Levin J, Miller K, Reynolds C, Macdonell R, Pasek M, Lee SJ, Ho V, Soiffer R, Antin JH, Ritz J, Alyea E.Rituximab for steroid-refractory chronic graft-versus-host disease.Blood 200
  16551963
• Ho VT, Kim HT, Liney D, Milford E, Gribben J, Cutler C, Lee SJ, Antin JH, Soiffer RJ, Alyea EP.HLA-C mismatch is associated with inferior survival after unrelated donor non-myeloablative hematopoietic stem cell transplantation.Bone Marrow Transplant 2006
  16532020
• Cutler C, Henry NL, Magee C, Li S, Kim HT, Alyea E, Ho V, Lee SJ, Soiffer R, Antin JH.Sirolimus and thrombotic microangiopathy after allogeneic hematopoietic stem cell transplantation.Biol Blood Marrow Transplant 2005 Jul;11(7):551-7.
  15983555
• 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 Oct 15;106(8):2903-11.
  15972448
• Alyea EP, Soiffer RJ, Canning C, Neuberg D, Schlossman R, Pickett C, Collins H, Wang Y, Anderson KC, Ritz J.Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant.Blood 1998 May
  9573003
• Wen PY, Alyea EP, Simon D, Herbst RS, Soiffer RJ, Antin JH.Guillain-Barré syndrome following allogeneic bone marrow transplantation.Neurology 1997 Dec;49(6):1711-4.
  9409375
• Claret EJ, Alyea EP, Orsini E, Pickett CC, Collins H, Wang Y, Neuberg D, Soiffer RJ, Ritz J.Characterization of T cell repertoire in patients with graft-versus-leukemia after donor lymphocyte infusion.J Clin Invest 1997 Aug 15;100(4):855-66.
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