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. These relevant problems include recurrence of the underlying disease, graft-versus-host disease (GVHD) and infections with cytomegalovirus (CMV) and/or varicella zoster virus (VZV). The program consists of one clinical and six experimental projects, as well as two cores. The clinical project deals with attempts to eradicate leukemias and lymphomas and prospectively evaluate drug or drug combinations intended to prevent serious transplant related complications such as acute or chronic GVHD and CMV associated interstitial pneumonia. Novel marrow cell preparations (allogeneic and autologous) will be explored for their capacity to successfully restore hematopoiesis and lymphopoiesis in patients with leukemia or lymphoma. The clinical project serves as a resource for the experimental projects of the program. The six experimental projects address the following biologically important transplant-related problems and topics: detection of minimal malignant disease; manipulation of allogeneic donor marrow to reduce GVHD and to preserve graft-versus-leukemia activity; purification of the human hematopoietic stem cell; peri-transplant idiotype vaccination for patients with B cell lymphoma; tumor specific cytotoxic T lymphocytes in marrow graft recipients; protective immunity to VZV after allogeneic and autologous BMT. The seven inter-related projects of this application are support by two cores, one for administration and coordination of research in this Program Project, and one providing biostatistical expertise.
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