Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells

J. N. Winter*, H. M. Lazarus, A. Rademaker, M. Villa, C. Mangan, M. Tallman, L. Jahnke, L. Gordon, S. Newman, K. Byrd, B. W. Cooper, N. Horvath, E. Crum, E. A. Stadtmauer, E. Conklin, A. Bauman, J. Martin, C. Goolsby, S. L. Gerson, J. BenderM. O'Gorman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Purpose: To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony- stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs). Materials and Methods: Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 μg/kg an days 1 to 12 and GM-CSF at .5, 1, or 5 μg/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 μg/kg on days 1 to 12 and G-CSF 5 μg/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 μg/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU- GM) and erythroid burst-forming units (BFU-E) were performed on each harvest. Results: The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 ± 8.9- and 33.7 ± 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001). Conclusion: Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.

Original languageEnglish (US)
Pages (from-to)277-286
Number of pages10
JournalJournal of Clinical Oncology
Volume14
Issue number1
DOIs
StatePublished - Jan 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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