OPTIMIZING DOSE AND SCHEDULING OF FILGRASTIM (GRANULOCYTE-COLONY-STIMULATING FACTOR) FOR MOBILIZATION AND COLLECTION OF PERIPHERAL-BLOOD PROGENITOR CELLS IN NORMAL VOLUNTEERS
- Author(s)
- Grigg, AP; Roberts, AW; RAUNOW, H; HOUGHTON, S; Layton, JE; Boyd, AW; McGrath, KM; MAHER, D;
- Details
- Publication Year 1995-12-15,Volume 86,Issue #12,Page 4437-4445
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- Abstract
- To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) far 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 mu g/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 (CI) 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 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 age or sex. Leukapheresis products obtained at the 10 mu g/ kg/d dose level 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+ cells per milliliter of blood on the day of leukapheresis predicted the total 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 experience with autologous PBPC transplantation), all seven leukapheresis products obtained at the 10 mu g/kg/d dose level were potentially sufficient for allogeneic transplantation purposes. We conclude that in normal donors, filgrastim 10 mu g/kg/d for 5 days with a single leukapheresis on the following day is a highly effective regimen for PBPC mobilization and collection. Further studies are required to determine whether PBPC collected with this regimen reliably produce rapid and sustained engraftment in allogeneic recipients. (C) 1995 by The American Society of Hematology.
- Publisher
- W B SAUNDERS CO
- Keywords
- PLATELET RECOVERY; G-CSF; CHEMOTHERAPY; TRANSPLANTATION; CIRCULATION; MARROW
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- Refer to copyright notice on published article.
Creation Date: 1995-12-15 12:00:00