The overall goal of this Program Project is to improve the outcome of allogeneic bone marrow transplantation (BMT) in the treatment of hematologic malignancies. General topics which will be addressed by this Program Project include the eradication of malignancy, expansion of the donor pool, and the development of methods to diminish or prevent transplant-related complications. Eleven individual research projects are proposed which will work collaboratively on these topics: 1. Treatment of patients with myeloid malignancies with BMT from HLA- identical family members. 2. Treatment of patients with lymphoid malignancies with BMT from HLA- identical family members. 3. Alternative marrow donors for patients lacking an HLA-identical family member. 4. Prevention and treatment of graft-versus-host disease. 5. Virus-mediated myelosuppression. 6. Hematopoietic growth factors in BMT. 7. Detection of minimal residual disease. 8. Pathophysiology and prevention of multiorgan failure after BMT. 9. Prevention and treatment of infection. 10. Specific adoptive immunotherapy of human disease with T-cell clones. 11. Induction or amplification of a graft-versus-leukemia effect by lymphokines and lymphocytes. Our ability to carry out the studies proposed in this Program Project is enhanced by: 1) preclinical research programs which focus on murine or canine models and allow rapid and logical translation of preclinical concepts to phase I clinical trials, 2) the accrual of on average 325 allogeneic transplant patients onto research studies each year, 3) supportive care programs in biostatistics, pathology, microbiology, pharmacology, transfusion care, critical care, gastroenterology, oral medicine, nutrition, social services, long-term follow-up and administration, and 4) our unique structure as a large group of investigators all of whom are focused on the general topic of BMT. Success in the achievement of the goal of this Program Project will likely have relevance for the use of other intensive therapies to treat hematologic malignancies, for the wider application of transplantation in the treatment of other malignant, and nonmalignant diseases and for the care of immunocompromised patients.
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