OPTIMIZING DOSE AND SCHEDULING OF FILGRASTIM (GRANULOCYTE-COLONY-STIMULATING FACTOR) FOR MOBILIZATION AND COLLECTION OF PERIPHERAL-BLOOD PROGENITOR CELLS IN NORMAL VOLUNTEERS

To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) far use in allogeneic transplantation. w e evaluated the kinetics of mobilization by filgrastim (recombinant me t-human granulocyte colony-stimulating factor [r-metHuG-CSF]) in norma l volunteers. Filgrastim was injected subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10 mu g/kg/d (n = 15). A subse t of volunteers from each dose cohort underwent a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte-macrophage colon y-forming cell (GM-CFC) numbers in the blood were maximal after 5 days of filgrastim; a broader peak was evident for CD34+ cells between day s 4 and 6. The 95% confidence intervals (CI) for mean number of PBPC p er milliliter of blood in the three dose cohorts overlapped on each st udy day. However, on the peak day, CD34+ cells were significantly high er in the 10 mu g/kg/ d cohort than in a pool of the 3 and 5 mu g/kg/d cohorts. Mobilization was not significantly influenced by volunteer a ge or sex. Leukapheresis products obtained at the 10 mu g/ kg/d dose l evel contained a median GM-CFC number of 93 x 10(4)/kg (range, 50 x 10 (4)/kg to 172 x 10(4)/kg). Collections from volunteers receiving lower doses of filgrastim contained a median GM-CFC number of 36 x 10(4)/kg (range, 5 x 10(4)/kg to 204 x 10(4)/kg). The measurement of CD34+ cel ls per milliliter of blood on the day of leukapheresis predicted the t otal yield of PBPC in the leukapheresis product (r = .87, P < .0001). Assuming a minimum GM-CFC requirement of 50 x 10(4)/kg (based on our e xperience with autologous PBPC transplantation), all seven leukapheres is products obtained at the 10 mu g/kg/d dose level were potentially s ufficient for allogeneic transplantation purposes. We conclude that in normal donors, filgrastim 10 mu g/kg/d for 5 days with a single leuka pheresis on the following day is a highly effective regimen for PBPC m obilization and collection. Further studies are required to determine whether PBPC collected with this regimen reliably produce rapid and su stained engraftment in allogeneic recipients. (C) 1995 by The American Society of Hematology.