Optimizing dose and scheduling of filgrastim (Granulocyte colony-stimulating factor) for mobilization and collection of peripheral blood progenitor cells in normal volunteers

Abstract

To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) for use in allogeneic transplantation, we evaluated the kinetics of mobilization by filgrastim (recombinant met-human granulocyte colony-stimulating factor [r-metHuG-CSF]) in normal volunteers. Filgrastim was injected subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10 μg/kg/d (n = 15). A subset of volunteers from each dose cohort underwent a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte-macrophage colony-forming cell (GM-CFC) numbers in the blood were maximal after 5 days of filgrastim; a broader peak was evident for CD34+ cells between days 4 and 6. The 95% confidence intervals (Cl) for mean number of PBPC per milliliter of blood in the three dose cohorts overlapped on each study day. However, on the peak day, CD34+ cells were significantly higher in the 10 μg/kg/ d cohort than in a pool of the 3 and 5 μg/kg/d cohorts. Mobilization was not significantly influenced by volunteer age or sex. Leukapheresis products obtained at the 10 μg/ kg/d dose level contained a median GM-CFC number of 93 × 104/kg (range, 50 × 104/kg to 172 × 104/kg). Collections from volunteers receiving lower doses of filgrastim contained a median GM-CFC number of 36 × 104/kg (range, 5 × 104/kg to 204 × 104/kg). The measurement of CD34+ cells per milliliter of blood on the day of leukapheresis predicted the total yield of PBPC in the leukapheresis product (r = .87, P