Characterization of peripheral blood progenitor cells (PBPC) mobilized by filgrastim (rHuG-CSF) in normal volunteers: Dose-effect relationship for filgrastim with the character of mobilized PBPC

Filgrastim (rHuG-CSF)-mobilized peripheral blood progenitor cells (PBPC) in healthy Japanese volunteers were characterized in detail using two clonal cell culture systems and double-colour now cytometry to detect multilineage colony-forming cells and subsets of CD34(+) cells, The kinetics of PBPC during the administration of filgrastim was studied, and possible differences in the character of progenitor cells relative to given doses of filgrastim were investigated. Filgrastim was administered subcutaneously to normal volunteers for 7 d at doses of 100, 200 or 400 mu g/m(2) (10 per cohort). Treatment with 100 or 200 mu g/m(2) filgrastim was well tolerated; however, the 400 mu g/m(2) dose level was not completed because of bone pain and myalgia, The treatment strikingly mobilized various types of progenitor cells, including highly proliferative megakaryocytic colony-forming cells, The number of progenitor cells peaked on days 5 and 6. The fold increase of circulating progenitor cells from the baseline value in the volunteers treated with 200 mu g/m(2) filgrastim was more pronounced than in those treated with 100 mu g/m(2). Treatment with 200 mu g/m(2) also released the less mature progenitor cells (i.e. mixed colony-forming cells, CD34(+)/33(-) cells, and CD34(+)/HLA-DR(-) cells) into circulation better than the 100 mu g/m(2) dose. These results suggest that daily subcutaneous injection with 200 mu g/m(2) filgrastim for 5 d will effectively mobilize, both qualitatively and quantitatively, PBPC in healthy donors.