ANALYSIS OF BMT CONDITIONING, CYTOKINES, GVHD AND GVL

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DESCRIPTION: (Applicant's Description) Our preliminary data demonstrate that the intensity of the conditioning regimen correlates with systemic levels of endotoxin, TNFalpha and IL-1 which significantly amplify GVHD. Using murine BMT models, we propose to investigate novel strategies to modulate this cytokine cascade, and to determine the extent to which individual target organ pathology correlates with changes in systemic GVHD. Our specific aims are: 1) To evaluate the ability of IL-I 1 and keratinocyte growth factor to prevent GVHD after intensively conditioned allogeneic BMT. 2) To compare conditioning regimens prior to allogeneic BMT for their effects on inflammatory cytokines. 3) To analyze blockade of inflammatory cytokines (both directly and indirectly) as a strategy to separate GVL from GVHD.