Brugger W, Birken R, Bertz H, Hecht T, Pressler K, Frisch J, Schulz G, Mertelsmann R, Kanz L
Albert-Ludwigs-University Medical Centre, Department of Haematology and Oncology, Freiburg, Germany.
Br J Haematol. 1993 Jul;84(3):402-7. doi: 10.1111/j.1365-2141.1993.tb03093.x.
We report on the chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood progenitor cells (PBPCs) and their impact on haematopoietic recovery following high-dose chemotherapy. Twenty-four patients with advanced solid tumours or lymphomas received standard-dose chemotherapy with VP16, ifosfamide and cisplatin (VIP) followed by filgrastim (G-CSF; 5 micrograms/kg s.c. daily for 14 d) for the prevention of chemotherapy induced neutropenia and for the simultaneous mobilization of PBPCs. Maximal numbers of progenitors of different lineages were reached at day 11 (range 9-14) after VIP chemotherapy. A median of 0.415 x 10(9)/l CD34+ cells (range 0.11-1.98), 9000 CFU-GM/ml (range 2800-17,700), 3500 BFU-E/ml (range 400-10,800) and 200 CFU-GEMM/ml (range 0-4400) were recruited. One single apheresis yielded a median of 1.6 x 10(8) mononuclear cells/kg (range 0.2-5.4) or 5.4 x 10(6) CD34+ cells/kg body weight (range 0.2-24.2). Fourteen patients who showed at least a partial remission after two cycles of the standard-dose chemotherapy regimen were subjected to high-dose VIP chemotherapy (cumulative doses of 1500 mg/m2 VP16, 12 g/m2 ifosfamide and 150 mg/m2 cisplatin) with or without PBPC support. The first six patients were treated with growth factors only (IL-3/GM-CSF) and did not receive PBPCs, whereas the following eight patients were supported with PBPCs in addition to IL-3 and GM-CSF. Neutrophil recovery as well as platelet recovery were significantly faster in patients receiving PBPCs with a median of 6.5 d below 0.1 x 10(9) neutrophils/l and 3 d below 20 x 10(9) platelets/l as compared to 10.5 d and 8 d in control patients receiving growth factors only. The accelerated platelet recovery in patients supported with PBPCs might be explained--in the absence of detectable colony-forming units megakaryocyte--by the presence of glycoprotein IIb/IIIa+, non-proliferating endomitotic megakaryocytic precursor cells within G-CSF mobilized PBPCs. Our data demonstrate that chemotherapy plus G-CSF mobilized PBPCs accelerate both neutrophil and platelet recovery after high-dose VIP chemotherapy in patients with solid tumours or lymphomas.
我们报告了化疗联合粒细胞集落刺激因子（G-CSF）诱导外周血祖细胞（PBPCs）动员及其对大剂量化疗后造血恢复的影响。24例晚期实体瘤或淋巴瘤患者接受了含依托泊苷、异环磷酰胺和顺铂（VIP）的标准剂量化疗，随后给予非格司亭（G-CSF；5微克/千克皮下注射，每日14天），以预防化疗引起的中性粒细胞减少并同时动员PBPCs。VIP化疗后第11天（范围9 - 14天）达到不同谱系祖细胞的最大数量。募集到的CD34 +细胞中位数为0.415×10⁹/升（范围0.11 - 1.98），CFU - GM为9000个/毫升（范围2800 - 17700），BFU - E为3500个/毫升（范围400 - 10800），CFU - GEMM为200个/毫升（范围0 - 4400）。单次采集的中位数为1.6×10⁸个单核细胞/千克（范围0.2 - 5.4）或5.4×10⁶个CD34 +细胞/千克体重（范围0.2 - 24.2）。14例在两个周期标准剂量化疗方案后至少达到部分缓解的患者接受了大剂量VIP化疗（依托泊苷累积剂量1500毫克/平方米、异环磷酰胺12克/平方米和顺铂150毫克/平方米），有或没有PBPC支持。前6例患者仅用生长因子（IL - 3/GM - CSF）治疗，未接受PBPCs，而接下来的8例患者除IL - 3和GM - CSF外还接受了PBPCs支持。接受PBPCs的患者中性粒细胞恢复以及血小板恢复明显更快，中性粒细胞低于0.1×10⁹/升的中位数为6.5天，血小板低于20×10⁹/升的中位数为3天，而仅接受生长因子的对照患者分别为10.5天和8天。在接受PBPCs支持的患者中，血小板恢复加速可能的解释是——在未检测到巨核细胞集落形成单位的情况下——G-CSF动员的PBPCs中存在糖蛋白IIb/IIIa +、非增殖性核内有丝分裂巨核细胞前体细胞。我们的数据表明，化疗联合G-CSF动员的PBPCs可加速实体瘤或淋巴瘤患者大剂量VIP化疗后的中性粒细胞和血小板恢复。
