This program project grant application seeks support for clinical and experimental studies concerning the major obstacles to successful allogeneic and autologous bone marrow transplantation (BMT) for hematologic malignancies, the leukemias and lymphomas. These relevant problems include recurrence of the underlying malignancies, viral infections and graft-versus-host disease (GVHD). The program consists of two clinical and eight experimental projects deal with novel preparatory regimens to eradicate leukemias and lymphomas and prospectively evaluate drug or drug combinations intended to prevent serious transplant related complications such as GVHD and human cytomegalovirus (HCMV) associated interstitial pneumonia. These two clinical projects serve as a resource for the eight experimental projects of the program. The experimental projects address the following biologically important transplant-related problems and topics: Detection of Minimal Malignant Disease; Combined Allogeneic and Autologous BMT (Resulting in Mixed Chimerism) and the Regulatory action of Natural Suppressor Cells; Isolation of Human Stem Cells; Relevance of the Multidrug Resistance Gene in Clinical BMT; Characterization of Tumor Specific Cytolytic T Lymphocytes in Marrow Graft Recipients; Peri-BMT Idiotype Vaccination in B Cell Lymphomas; Pathogenesis and Immunity of Varicella Zoster Virus Infections After BMT; Delivery of a New Antiviral Agent (DHPG) Using HCMV-Monoclonal Antibody Coated Liposomes. The ten inter-related projects of this application are supported by two cores, one providing biostatistical expertise and one concerning administration as well as coordination of research in this program project grant.
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