This project will study the use of recombinant cytokines to accelerate hematopoietic recovery following autologous marrow transplantation. In patients with non-myeloid neoplasia, the studies will be focused on decreasing the period of absolute neutropenia observed even when marrow infusion is followed by recombinant G- or GM-CSF. A second goal is to accelerate platelet recovery. Our initial strategy will be to test the effect of peripheral blood progenitor (stem) cells (PBSC) mobilized by various cytokines in a series of sequential trials. The purpose will be to examine the effect of adding PBSC to bone marrow on time to neutrophil and platelet recovery. Following these trials, the effect of a short course of early acting cytokines such as IL-3 or the IL-3-GM-CSF fusion molecule prior to marrow harvest on time to reconstitution will be tested. Quantitative assays for committed, multipotent, and long-term marrow culture repopulating progenitor cells will be performed on marrow and blood cells in patients receiving cytokines for PBSC collection to evaluate their effects. Lastly, we will test the hypothesis that pharmacologically blocking negative regulatory molecules such as tumor necrosis factor will accelerate engraftment. A parallel series of trials will be performed in patients undergoing AMT for myeloid neoplasia. Initial trials in AML will evaluate the effect of IL-1 and IL-1 + GM-CSF given after marrow infusion. A second study will examine the effect of PBSC added to marrow in patients at high risk for poor grafts due to poor marrow cell yields.
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