PHASE I II STUDY OF COMBINED GRANULOCYTE-COLONY-STIMULATING FACTOR AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR ADMINISTRATION FOR THE MOBILIZATION OF HEMATOPOIETIC PROGENITOR CELLS/

Purpose: To study the toxicity and efficacy of combined granulocyte co lony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stim ulating factor (GM-CSF) administration for mobilization of hematopoiet ic progenitor cells (HPCs). Materials and Methods: Cohorts of a minimu m of five patients each were treated subcutaneously as follows: G-CSF 5 mu g/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 mu g/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 mu g/kg on days 1 to 12 and G-CS F 5 mu g/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 mu g/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed o n days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for gran ulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-f orming units (BFU-E) were performed on each harvest. Results: The prin cipal toxicities were myalgias, bone pain, fever, nausea, and mild thr ombocytopenia, but none was dose limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases i n the numbers of CFU-GM per kilogram collected per harvest that repres ented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, re spectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased con centrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HP C content to surge to nearly 80-fold the baseline (P = .024); the reve rse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maxi mal mobilization achieved (r = .74, P = .001). Conclusion: Combined G- CSF and GM-CSF administration effectively and predictably mobilizes HP Cs and facilitates apheresis. (C) 1996 by American Society of Clinical Oncology.