Multilineage mobilization of peripheral blood progenitor cells in humans following administration of PEG-rHuMGDF

The most important physiological regulator of megakaryocytopoiesis is the ligand for the c-mpl receptor (thrombopoietin/megakaryocyte growth and development factor, MGDF). We examined the effect of pegylated-recombinant human MGDF (PEG-rHuMGDF): patients received PEG-rHuMGDF at doses of 0.03, 0.1, 0.3 or 1.0 μg/kg/d or placebo for 10 d maximum in a double-blinded randomized study. There was a dose-dependent elevation in circulating platelet counts but no alteration in erythrocyte or total leucocyte counts. The number of bone marrow megakaryocytes was increased approximately 2-fold. The frequency of bone marrow progenitor cells was not altered. In contrast, both to the bone marrow results and to published pre-clinical data, there was a dose-dependent mobilization into the blood of progenitor cells of multiple cell lineages. Increased levels of Meg-CFC (maximum increase 30-fold), day 7 and day 14 GM-CFC and BFU-E were demonstrated at doses of 0.3 and 1.0 μg/kg/d PEG-rHuMGDF. At 0.1 μg/kg/d, mobilization of Meg-CFC alone occurred in two-thirds of patients. Maximum blood levels of progenitor cells occurred at day 12. Thus, administration of PEG-rHuMGDF to humans resulted in mobilization of progenitor cells of multiple lineages despite its 'lineage-specific' activity on mature cell development.