The goal of our studies is to achieve further progress in the areas of allogeneic transplantation which would result in improved disease free survival and cure rates by a) Decreasing the leukemia relapse rate following marrow grafting; b) Reducing the incidence of acute and chronic graft-versus-host disease; c) Preventing the development of CMV associated interstitial pneumonia; and d) Decreasing the complications of the preparatory regimen. To this end we propose five clinical trials in this project entitled """"""""Allogeneic Bone Marrow Transplantation for Hematologic Malignancy"""""""". We propose to conduct a series of Phase I, II and III trials designed to improve the efficacy and reduce the toxicity of the preparatory regimen used for patients undergoing allogeneic marrow transplantation. In addition, we will continue and extend our trials in the chemoprophylaxis of acute graft-versus-host disease after both related and unrelated bone marrow transplantation. We will also conduct trials to address the infectious complications of marrow transplantation by improving the prophylaxis of cytomegalovirus infection utilizing either pharmacologic or immunologic methods and we will explore novel approaches to the prevention of fungus infection after marrow transplantation. Four of the five specific aims will be carried out jointly at the City of Hope National Medical Center and at Stanford University. In the past, these two institutions have collaborated closely in clinical trials which have yielded promising results. The hypothesis to be tested is that the regimens described in this proposal may lead to results which are superior to those obtained with other widely utilized approaches and will increase the safety of the therapy. We have proposed prospective trials to define the role of new regimens used to ablate leukemia and prevent graft-versus- host disease and infection that have been developed from research performed by the investigators in this Program Project Grant.
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