The overall goal of this Program Project is to improve the outcome of autologous marrow transplantation (AMT) in the treatment of hematologic malignancies. General topics which will be addressed by this Program Project include the eradication of malignancy, the clonality of hematopoiesis, the effects of peripheral blood progenitors on engraftment, effects of growth factors and attempts to block in vivo growth inhibitors. Seven individual research projects are proposed which will work collaboratively on these topics: 1.Evaluation of AMT. a.Acute lymphoblastic leukemia and malignant lymphoma. b.Acute myeloid leukemia. 2.Contribution of genetically marked peripheral blood repopulating cells to hematopoietic reconstitution after AMT. 3.Hematopoietic growth factors: preclinical evaluation. 4.Colony Forming Cells: generation from precursors in Acute Myeloid Leukemia. 5.Clonal hematopoiesis: an evaluation of clonal origins in malignancy and hematopoiesis. 6.Growth factors in autologous marrow transplant. 7.Evaluation of Lymphokines and Adoptive immunotherapy following AMT. Our ability to carry out the studies proposed in this Program Project is enhanced by: 1) preclinical research programs which focus on murine, canine, or non-human primate models and allow rapid and logical translation of preclinical concepts to clinical trials, 2) the accrual of over 120 autologous transplant patients onto research studies each year, 3) supportive care programs in biostatistics, marrow processing, outpatient and long-term follow-up, pathology, infectious disease consulting, pharmacology, nutrition services, transfusion support and administration, and 4) a unique structure as a large group of investigators all of whom are focused on the general topic of marrow transplantation. Success in achieving the goals of this Program Project will have relevance for the use of other intensive therapies to treat hematologic malignancies, for the wider application of AMT in the treatment of other malignant and nonmalignant diseases, and for the care of pancytopenic and immunocompromised patients.
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