We propose to continue a program of laboratory and clinical research directed at improving the results of marrow transplantation in patients with hematologic malignancies. This proposal supports investigators involved in studies aimed at improving the therapeutic potential of marrow transplantation by: (1) conducting phase I studies of new chemoradiotherapy regimens designed to have a greater anti-neoplastic effect with reduced toxicity; (2) carrying out phase III studies to define optimal regimens in large numbers of patients; (3) developing effective measures to decreasing graft-versus-host disease and thereby decreasing morbidity and mortality; (4) developing more effective methods for prevention and treatment of viral, bacterial and fungal diseases. We will investigate the extension of transplantation of marrow donors other than HLA matched siblings and the histocompatibility factors that govern success or failure. This proposal will also evaluate fundamental questions related to chimerism, origin of leukemic relapse, immunologic recovery and tolerance, in vitro hematopoiesis, monoclonal antibody application, nutritional problems, transfusion support and pulmonary and gastrointestinal complications. The pathology of graft-versus-host disease, venocclusive disease of the liver, and viral infections will be further defined including the use of molecular probes for rapid diagnosis. Biostatisticians will participate in the design and analysis of all studies. A data base management system will allow us to make maximal use of the large number of studies to be performed. Outpatient studies will define the long-term effects of marrow transplantation and will explore the feasibility of enhanced outpatient care to facilitate early discharge from hospital and thus reduce the cost of marrow transplantation.
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