Peters W P, Rosner G, Ross M, Vredenburgh J, Meisenberg B, Gilbert C, Kurtzberg J
Duke University Bone Marrow Transplant Program, Durham, NC 27710.
Blood. 1993 Apr 1;81(7):1709-19.
Two hematopoietic colony-stimulating factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF), have been shown to accelerate leukocyte and neutrophil recovery after high-dose chemotherapy and autologous bone marrow (BM) support. Despite their use, a prolonged period of absolute leukopenia persists during which infections and other complications of transplantation occur. We collected large numbers of peripheral blood (PB) progenitors after CSF administration using either G-CSF or GM-CSF and tested their ability to affect hematopoietic reconstitution and resource utilization in patients undergoing high-dose chemotherapy and autologous BM support. Patients with breast cancer or melanoma undergoing high-dose chemotherapy and autologous BM support were studied in sequential nonrandomized trials. After identical high-dose chemotherapy, patients received either BM alone, with no CSF; BM with either G-CSF or GM-CSF; or BM with G-CSF or GM-CSF and G-CSF or GM-CSF primed peripheral blood progenitor cells (PBPC). Hematopoietic reconstitution, as well as resource utilization, was monitored in these patients. The use of CSF-primed PBPC led to a highly significant reduction in the duration of leukopenia with a white blood cell (WBC) count under 100 and 200 cells/mL, and neutrophil count under 100 and 200 cells/mL with both GM- and G-CSF primed PB progenitor cells, compared with the use of the CSF with BM or with historical controls using BM alone. In addition, the use of CSF-primed PBPC resulted in a significant reduction in median number of antibiotics used, days in the Bone Marrow Transplant Unit, and hospital resources used. Patients receiving G-CSF primed PBPC also experienced a reduction in the median number of days in the hospital, red blood cell (RBC) transfusions, platelet transfusions, days on antibiotics, and discounted hospital charges. Phenotypic analysis of the CSF-primed PBPC indicated the presence of cells bearing antigens associated with both early and late hematopoietic progenitor cells. The use of CSF-primed PBPC can significantly improve hematopoietic recovery after high-dose chemotherapy and autologous BM support. In addition, the use of G-CSF-primed PBPC was associated with a significant reduction in hospital resource utilization, and a reduction in hospital charges.
两种造血集落刺激因子,即粒细胞集落刺激因子(G-CSF)和粒细胞巨噬细胞集落刺激因子(GM-CSF),已被证明可加速大剂量化疗及自体骨髓(BM)支持后白细胞和中性粒细胞的恢复。尽管使用了这些因子,但在移植过程中仍会持续一段较长时间的绝对白细胞减少期,在此期间会发生感染及其他移植相关并发症。我们在使用G-CSF或GM-CSF给予集落刺激因子后收集了大量外周血(PB)祖细胞,并测试了它们对接受大剂量化疗及自体BM支持患者的造血重建和资源利用的影响。在连续的非随机试验中,对患有乳腺癌或黑色素瘤且接受大剂量化疗及自体BM支持的患者进行了研究。在相同的大剂量化疗后,患者分别接受以下治疗:仅接受BM,不使用集落刺激因子;接受BM加G-CSF或GM-CSF;或接受BM加G-CSF或GM-CSF以及经G-CSF或GM-CSF预处理的外周血祖细胞(PBPC)。对这些患者的造血重建及资源利用情况进行了监测。与使用BM加集落刺激因子或仅使用BM的历史对照相比,使用经集落刺激因子预处理的PBPC可显著缩短白细胞减少的持续时间,白细胞计数低于100和200细胞/毫升,以及中性粒细胞计数低于100和200细胞/毫升,无论是GM-CSF还是G-CSF预处理的PB祖细胞均如此。此外,使用经集落刺激因子预处理的PBPC可显著减少抗生素使用的中位数、在骨髓移植病房的天数以及医院资源的使用。接受G-CSF预处理PBPC的患者在住院天数中位数、红细胞(RBC)输血、血小板输血、使用抗生素天数以及医院费用折扣方面也有所减少。对经集落刺激因子预处理的PBPC进行表型分析表明存在带有与早期和晚期造血祖细胞相关抗原的细胞。使用经集落刺激因子预处理的PBPC可显著改善大剂量化疗及自体BM支持后的造血恢复。此外,使用G-CSF预处理的PBPC与医院资源利用的显著减少以及医院费用的降低相关。