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Patients undergoing allogeneic hematopoeitic stem cell (HSC) transplantation are subject to severe immunodeficiency after transplant, particularly with the use of T cell depletion as the method of graft-versus-host-disease (GVHD) prophylaxis. This immunodeficiency results in significant morbidity and mortality from infections, especially in adults.

We are currently investigating multiple approaches to enhance immune reconstitution in the laboratory and have recently moved one of these strategies to the clinic. In preclinical mouse models of allogeneic T cell depleted bone marrow transplantation(BMT) we have shown that posttransplant administration of the "lymphoid growth factor" Interleukin-7 (IL-7) can enhance thymopoiesis as well as promote peripheral T cell expansion without causing GVHD.1-2 Therefore, we are conducting a Phase I clinical trial of post-transplant administration of recombinant human IL-7 (CYT 99 007, Cytheris, Inc.) in recipients of an HLA-matched T cell depleted HSC transplant to determine the safety, toxicity, and biological activity of IL-7 on T cell reconstitution. The study includes recipients of a T cell depleted transplant from a 6/6 HLA-identical related or unrelated donor after myeloablative conditioning for the treatment of a nonlymphoid hematological malignancy. We predict that administration of IL-7 will promote T cell reconstitution and decrease morbidity and treatment- related mortality following allogeneic transplant.

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