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

Rasko, JEJ; Basser, RL; Boyd, J; Mansfield, R; OMalley, CJ; Hussein, S; Berndt, MC; Clarke, K; OByrne, J; Sheridan, WP; Grigg, AP; Begley, CG

Author(s): Rasko, JEJ; Basser, RL; Boyd, J; Mansfield, R; OMalley, CJ; Hussein, S; Berndt, MC; Clarke, K; OByrne, J; Sheridan, WP; Grigg, AP; Begley, CG;
Details: Publication Year 1997-06,Volume 97,Issue #4,Page 871-880
Journal Title: BRITISH JOURNAL OF HAEMATOLOGY
Publication Type: Journal Article
Abstract: 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 mu g/kg/d or placebo for 10d 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 mu g/kg/d PEG-rHunlIGDE At 0.1 pg/kg/d, mobilization of Meg-CEC 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.
Publisher: BLACKWELL SCIENCE LTD
Keywords: C-MPL LIGAND; COLONY-STIMULATING FACTOR; MEGAKARYOCYTE GROWTH; IN-VITRO; INDUCED THROMBOCYTOPENIA; PLATELET PRODUCTION; G-CSF; THROMBOPOIETIN; CHEMOTHERAPY; CLONING
Publisher's Version: https://doi.org/10.1046/j.1365-2141.1997.1212937.x
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Creation Date: 1997-06-01 12:00:00