MOBILIZATION OF PERIPHERAL-BLOOD STEM-CELLS BY SUBCUTANEOUS INJECTIONS OF YEAST-DERIVED GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR - A PHASE-I-II STUDY

A phase I-II study was conducted in 15 patients to determine the tolerability, efficacy and optimal dose of s.c. yeast-derived granulocyte-macrophage colony stimulating factor (GM-CSF) for mobilization of peripheral blood stem cells (PBSC). PBSC were measured by the colony forming unit granulocyte-macrophage (CFU-GM) and burst forming unit erythroid (BFU-E) in vitro colony assays and CD34 flow cytometric analysis. GM-CSF was administered for 12 days as a single daily s.c. injection at 125 mug/M2 (n = 3), 250 mug/M2 (n = 3), 375 mug/M2 (n = 6) and 500 mug/M2(n = 3). At these doses, sustained serum GM-CSF levels of approximately 100-400 pg/ml were observed for at least six hours. Most (97.2% or 175/180) of the planned GM-CSF doses were administered with no serious adverse effects at any of the dose levels. Three leukapheresis procedures were performed before and then after 8, 10 and 12 doses of s.c. GM-CSF. Compared with basal leukapheresis collections, s.c. GM-CSF mobilized leukapheresis collections yielded greater numbers of total white blood cells ([WBC] 15/15 patients or 100%, p < 0.001) mononuclear cells ([MNC] 8/15 patients or 53%, p = 0.55), CFU-GM (11/15 patients or 73%, p = 0.037), BFU-E (9/15 patients or 60 %, p = 0.13) and CD34+ cells (6/15 patients or 40%,p = 0.15). The in vitro CFU-GM were augmented approximately two to tenfold in GM-CSF mobilized collections with no clear dose effects from 125-500/mug/M2. However, in vivo engraftment time to absolute neutrophil count (ANC) 500/mm3 correlated strongly with GM-CSF PBSC mobilizing dose (r2 = 0.99). We conclude that s.c. yeast-derived GM-CSF is a simple, effective and tolerable method for mobilization of PBSC.