Paclitaxel vs cyclophosphamide in peripheral blood stem cell mobilization:Comparative studies in a murine model

Paclitaxel is a promising drug for the treatment of breast and ovarian canc er. It also may play a role in mobilization of peripheral blood stem cells (PBSC), as an alternative to cyclophosphamide (Cy). We investigated the PBS C-mobilizing potential of paclitaxel compared to Cy in a murine model. C57B l/6 mice were primed with intraperitoneal injections of Cy (200 mg/kg) or p aclitaxel (60 mg/kg) and were sacrificed 4, 6, 8, or 10 days later. Spleens were harvested and processed to obtain low-density mononuclear cells that were used as PBSC. The number of hematopoietic progenitors (CFU-C) on day 4 was significantly higher in the paclitaxel group when compared to mice rec eiving Cy (72.0 +/- 1.8 vs 9.8 +/- 2.8, p < 0.001). By day 6, CFU-C became significantly higher in the Cy-treated group compared to the paclitaxel-tre ated group (195.6 +/- 31.9 vs 95.8 +/- 20.7, p < 0.05) and this trend was m aintained. However, the total number of CFU-C recovered per spleen was grea ter in the paclitaxel-treated group (1.27 x 10(5) +/- 0.53 x 10(5) vs 1.06 x 10(5) +/- 0.36 x 10(5), NS). In contrast to paclitaxel, mobilization with Cy was associated with marked perturbation in the proportion of lymphoid c ell subsets in the PBSC population along with functional impairment of lymp hocytes. After 24 hours of in vitro IL-2 activation, the cytotoxic effector cell function of the Cymobilized PBSC population was lower than that of pa clitaxel-mobilized cells when tested against three tumor cell lines (B16, m elanoma; C1498, AML; and Yak-1, lymphoma). These results indicate that pacl itaxel is an efficient mobilizer of PBSC, leading to early (day 4 to 6) mob ilization of PBSC when compared to Cy (day 6 to 8). In addition, paclitaxel was associated with less perturbation of phenotypic and functional charact eristics of cells contained within the mobilized PBSC population. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Sc ience Inc.