TY - JOUR
T1 - Paclitaxel vs cyclophosphamide in peripheral blood stem cell mobilization
T2 - Comparative studies in a murine model
AU - Verma, Udit N.
AU - Van Den Blink, Bernt
AU - Pillai, Ravindran
AU - Chawla, Jasvinder
AU - Mazumder, Amitabha
AU - Herscowitz, Herbert B.
AU - Meehan, Kenneth R.
N1 - Funding Information:
This work was supported by a Vincent T. Lombardi Cancer Center Breast Cancer SPORE grant (P50 CA 58185). Bernt van den Blink participated in this work as an exchange student and was supported in part by the International Medical Students Exchange Program (IMSEP) and the Dr. Saal van Zwanenbergstichting Foundation.
PY - 1999/3
Y1 - 1999/3
N2 - Paclitaxel is a promising drug for the treatment of breast and ovarian cancer. It also may play a role in mobilization of peripheral bloodstem cells (PBSC), as an alternative to cyclophosphamide (Cy). We investigated the PBSC- mobilizing potential of paclitaxel compared to Cy in a murine model. C57B1/6 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 x 105 ± 0.53 x 105 vs 1.06 x 105 0.36 x 105, 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.
AB - Paclitaxel is a promising drug for the treatment of breast and ovarian cancer. It also may play a role in mobilization of peripheral bloodstem cells (PBSC), as an alternative to cyclophosphamide (Cy). We investigated the PBSC- mobilizing potential of paclitaxel compared to Cy in a murine model. C57B1/6 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 x 105 ± 0.53 x 105 vs 1.06 x 105 0.36 x 105, 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.
KW - Animal model
KW - Cyclophosphamide
KW - Paclitaxel
KW - Priming chemotherapy
KW - Stem cells
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U2 - 10.1016/S0301-472X(98)00044-7
DO - 10.1016/S0301-472X(98)00044-7
M3 - Article
C2 - 10089919
AN - SCOPUS:0033052289
SN - 0301-472X
VL - 27
SP - 553
EP - 560
JO - Experimental Hematology
JF - Experimental Hematology
IS - 3
ER -