Fleming D R, Goldsmith J, Goldsmith G H, Stevens D A, Herzig R H
University of Louisville Blood and Marrow Transplant Program, James Graham Brown Cancer Center, Room 230, 529 South Jackson Street, Louisville, KY 40202, USA.
J Hematother Stem Cell Res. 2000 Dec;9(6):855-60. doi: 10.1089/152581600750062282.
Chemotherapy, in addition to recombinant growth factors, has been effective in mobilizing stem cells. Unfortunately, the use of chemotherapy for this purpose has resulted in profound myelosuppression and increased morbidity. Docetaxel, the single most active agent in the treatment of advanced breast cancer, was evaluated for its potential to mobilize stem cells when given at conventional doses followed by granulocyte colony-stimulating factor (G-CSF). Sixteen high-risk breast cancer patients were mobilized with a regimen consisting of docetaxel (100 mg/m2) followed by daily G-CSF (10 microg/kg), beginning 72 h after the docetaxel, and continuing until completion of the apheresis. The median white blood cell count (WBC) nadir was 1,000/microl (range 500 to 4000/microl ) occurring a median of 6 days (range 4 to 9 days) after the docetaxel. No patient experienced a neutropenic febrile episode due to the mobilization regimen. The median time interval for initiating the apheresis was 8 days (range 6 to 11 days) following the docetaxel. The median number of apheresis was 2 (range 1 to 3) in each patient. Stem cell recovery as measured by the CD34 cell count x 10(6)/kg was a median of 5.2 (range 1.4 to 15.1). A significant correlation was found between CFU-GM, BFU-E, and CFU-GEMM/kg and CD34 cells/kg (r = 0.891, 0.945, and 0.749, respectively, p < 0.001). When our results were compared to a matched cohort receiving G-CSF alone, the docetaxel group demonstrated a superior CD34 cells/kg yield (p = <0.001). Following myeloablative chemotherapy consisting of thiotepa and cyclophosphamide with or without carboplatinum, the hematopoetic recovery determined by an absolute neutrophil count (ANC) of greater than 500/microl and an unsupported platelet count of > or =20,000/microl for 48 h, was a median of 10 days (range 9 to 14 days) and 10 days (range 8 to 30 days), respectively. The results demonstrate that conventional dose docetaxel, combined with G-CSF, is an effective mobilization regimen with minimal toxicity in high-risk breast cancer patients.
除重组生长因子外,化疗在动员干细胞方面也很有效。不幸的是,为此目的使用化疗已导致严重的骨髓抑制并增加了发病率。多西他赛是治疗晚期乳腺癌最有效的单一药物,评估了其在常规剂量给药后联合粒细胞集落刺激因子(G-CSF)时动员干细胞的潜力。16例高危乳腺癌患者采用多西他赛(100mg/m²)联合每日G-CSF(10μg/kg)的方案进行动员,G-CSF在多西他赛给药72小时后开始使用,并持续至采集结束。白细胞计数(WBC)最低点的中位数为1000/μl(范围为500至4000/μl),发生在多西他赛给药后的中位数为6天(范围为4至9天)。没有患者因动员方案出现中性粒细胞减少发热事件发生。开始采集的中位时间间隔为多西他赛给药后的8天(范围为6至11天)。每位患者采集的中位数为2次(范围为1至3次)。通过CD34细胞计数×10⁶/kg测量的干细胞恢复情况,中位数为5.2(范围为1.4至15.1)。发现CFU-GM、BFU-E和CFU-GEMM/kg与CD34细胞/kg之间存在显著相关性(r分别为0.891、0.945和0.749,p<0.001)。当将我们的结果与仅接受G-CSF的匹配队列进行比较时多西他赛组显示出更高的CD34细胞/kg产量(p=<0.001)。在接受含或不含卡铂 的噻替派和环磷酰胺的清髓性化疗后,通过绝对中性粒细胞计数(ANC)大于500/μl且无支持的血小板计数≥20,000/μl持续48小时来确定造血恢复情况,中位数分别为10天(范围为9至14天)和10天(范围为8至30天)。结果表明,常规剂量的多西他赛联合G-CSF是一种有效的动员方案,对高危乳腺癌患者的毒性最小。