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 (PBP C) in healthy Japanese volunteers were characterized in detail using t wo clonal cell culture systems and double-colour now cytometry to dete ct 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 relativ e to given doses of filgrastim were investigated. Filgrastim was admin istered subcutaneously to normal volunteers for 7 d at doses of 100, 2 00 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 leve l was not completed because of bone pain and myalgia, The treatment st rikingly mobilized various types of progenitor cells, including highly proliferative megakaryocytic colony-forming cells, The number of prog enitor cells peaked on days 5 and 6. The fold increase of circulating progenitor cells from the baseline value in the volunteers treated wit h 200 mu g/m(2) filgrastim was more pronounced than in those treated w ith 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 th e 100 mu g/m(2) dose. These results suggest that daily subcutaneous in jection with 200 mu g/m(2) filgrastim for 5 d will effectively mobiliz e, both qualitatively and quantitatively, PBPC in healthy donors.