SPID#: 28 Cancer chemotherapy is effective in curing or controlling many types of malignancies. A major side effect of most effective chemotherapy regimens has been marrow damage that results in low blood counts, leaving the patient more susceptible to infectious and hemorrhagic complications. Recombinant blood cell growth factors such as G-CSF or GM-CSF have been successful in accelerating the regrowth of white cells after chemotherapy, thereby reducing infections. The optimal way to stimulate post-chemotherapy recovery of platelet production has remained elusive. Recently, a new human blood cell growth factor, termed c-mpl ligand or thrombopoietin (TPO), has been cloned and appears to be the long sought cytokine that primarily regulates platelet production. The proposed studies will be among the first to employ recombinant human (rh) TPO in a large animal model. In a preliminary dose finding experiment, we administered rhTPO to normal monkeys by daily subcutaneous injection in doses varying over a 100 fold range, and monitored changes in peripheral blood counts. From these studies we observed a ten fold increase in circulating platelets after 14 days of rhTPO administration, and an optimal effective dose was determined. In a second set of studies, we administered rhTPO by daily injection for 10 days to normal rhesus macaques, and serially sampled blood and marrow to determine the longitudinal effects of rhTPO on multiple parameters of blood cell production. An analysis of these findings is currently underway.
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