This project proposes a program of experimental therapeutics, closely integrated with the different research projects of the program project, which is designed to address the major and continuing obstacles to successful application of marrow transplants to the treatment of hematopoietic malignancies: graft-versus-host disease (GvHD), the post- transplant complications of viral infections and leukemic relapse and the patient lacking an HLA-matched sibling donor. The series of protocols proposed has evolved from a stepwise progression of clinical trials and laboratory investigations conducted at our institution which have explored the unique biology of both HLA-identical and HLA-disparate T- cell depleted marrow transplants, defined their potential and developed strategies to overcome their current limitations. The protocols proposed are: I. A prospective randomized trial of T-cell depleted vs. unmodified marrow transplants in the treatment of acute leukemia in early remission. II. A phase II trial examining a novel cytoreductive regimen incorporating Thiotepa and anti-thymocyte globulin and an alternative techniques of T-cell depletion for HLA-matched sibling transplant applied to the treatment of chronic myelogenous leukemia. III. A phase II trial examining the same cytoreductive regimen used with T-cell deplete marrow grafts for patients with leukemia receiving transplant from HLA- partially matched related and histocompatible unrelated donors. IV. A phase II trial of CD33- specific radiolabelled monoclonal antibody coupled with busulfan and cyclophosphamide and an unmodified HLA-matched marrow graft for the treatment of patients with refractory or relapsed CD33+ AML or CML with CD33+ myeloid blast crisis. V. A phase I/II dose escalating trial of donor leukocytes for treatment of transplant recipients who have suffered cytogenetic and clinical relapses of CML. VI. A prospective randomized trial evaluating moderate dose Ganciclovir for preemptive treatment of asymptomatic patients developing CMV virus detectable by pcr amplified assays for CMV-DNA in circulating blood leukocytes.
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