Docetaxel-induced mobilization of hematopoietic stem cells in a murine model: Kinetics, dose titration, and toxicity

Objective. Docetaxel (DXT) is an anticancer agent that has demonstrated the rapeutic efficacy against solid tumors, particularly breast cancer. Based o n the use of hematopoietic stem cell (HSC) transplantation to restore hemat opoietic reconstitution after myeloablative therapy, this study was perform ed to determine if DXT could mobilize HSCs in vivo. Materials and Methods, C57Bl/6 mice were injected intraperitoneally with va rying doses of DXT (equivalent to human doses of 40 to 120 mg/m(2)). Spleen s were harvested on days 2, 4, 6, 8, 10, and 12 after DXT administration fo r recovery of mononuclear cells (MNCs), The number of HSCs present within t he MNCs was determined by clonogenic assay for colony-forming units in cult ure (CFU-C) and by FACS analysis for CD34(+) cells. Peripheral blood sample s were obtained at the time of spleen harvest to determine the hematologic profile. Liver and renal function tests were performed to monitor toxicity. Results, DXT mobilized HSCs in a dose- and time-dependent manner. When meas ured by the CFU-C assay, maximal mobilization of HSC (>10-fold increase ove r control; p < 0.01) was observed at a dose of 30 mg/kg (equivalent to huma n dose of 75 mg/m(2)) on day 7. The number of mobilized HSCs peaked on days 6 to 8 at all doses of DXT tested. There was no evidence of weight loss, l iver, or renal toxicity at any of the DXT doses tested, Conclusion, These results indicate that DXT efficiently mobilizes HSCs in a murine model and provide the rationale for similar studies in a clinical t rial. (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc.