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

Abstract

Paclitaxel is a promising drug for the treatment of breast and ovarian cancer. It also may play a role in mobilization of peripheral blood stem cells (PBSC), as an alternative to cyclophosphamide (Cy). We investigated the PBSC-mobilizing potential of paclitaxel compared to Cy in a murine model. C57Bl/6 mice were primed with intraperitoneal injections of Cy (200 mg/kg) or paclitaxel (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 receiving 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-treated group (195.6 ± 31.9 vs 95.8 ± 20.7, p < 0.05) and this trend was maintained. However, the total number of CFU-C recovered per spleen was greater in the paclitaxel-treated group (1.27 × 10 5 ± 0.53 × 10 5 vs 1.06 × 10 5 ± 0.36 × 10 5, NS). In contrast to paclitaxel, mobilization with Cy was associated with marked perturbation in the proportion of lymphoid cell subsets in the PBSC population along with functional impairment of lymphocytes. After 24 hours of in vitro IL-2 activation, the cytotoxic effector cell function of the Cy-mobilized PBSC population was lower than that of paclitaxel-mobilized cells when tested against three tumor cell lines (B16, melanoma; C1498, AML; and Yak-1, lymphoma). These results indicate that paclitaxel is an efficient mobilizer of PBSC, leading to early (day 4 to 6) mobilization of PBSC when compared to Cy (day 6 to 8). In addition, paclitaxel was associated with less perturbation of phenotypic and functional characteristics of cells contained within the mobilized PBSC population.