Bradstock K, Matthews J, Young G, Lowenthal R, Baxter H, Arthur C, Bashford J, Brighton T, Cannell P, Dunlop L, Durrant S, Enno A, Eliadis P, Gill D, Gillett A, Gottlieb D, Januszewicz H, Joshua D, Leahy M, Schwarer A, Taylor K
Haematology Department, Westmead Hospital, NSW, Australia.
Leukemia. 2001 Sep;15(9):1331-8. doi: 10.1038/sj.leu.2402218.
The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia (AML) intensified with high-dose cytarabine, and therefore improve response rates and survival. Patients were randomised to receive lenograstim (glycosylated recombinant human G-CSF) 5 microg per kg body weight subcutaneously daily from day 8 after starting chemotherapy, or no cytokine, following chemotherapy with cytarabine 3 g/m2 every 12 h on days 1, 3, 5, and 7, together with idarubicin 9 or 12 mg/m2 on days 1, 2, and 3, plus etoposide 75 mg/m2 on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia <0.5 x 10(9)/l compared to patients in the no cytokine arm (median 18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia <1.0 x 10(9)/l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P= 0.015) and a trend to reduced number of days with fever >38.0 degrees C (9 vs 12 days; P = 0.18). There were no differences between the two groups in platelet recovery, red cell or platelet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P = 0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P = 0.5), and there was no significant difference in the survival durations. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine, resulting in an improvement in a number of clinically important parameters with no major adverse effects.
澳大利亚白血病研究组（ALSG）研究了粒细胞集落刺激因子（G-CSF）是否会加速高剂量阿糖胞苷强化诱导治疗急性髓系白血病（AML）后的造血恢复，从而提高缓解率和生存率。患者被随机分组，从化疗开始后第8天起，每天皮下注射5微克/千克体重的来格司亭（糖基化重组人G-CSF），或不使用细胞因子；化疗方案为在第1、3、5和7天每12小时静脉注射3克/平方米阿糖胞苷，在第1、2和3天静脉注射9或12毫克/平方米伊达比星，在第1至7天（含第1天和第7天）静脉注射75毫克/平方米依托泊苷。患者为未经治疗的AML患者，年龄在16至60岁之间。总体而言，54例可评估患者被随机分配接受来格司亭治疗，58例接受无细胞因子治疗。与无细胞因子组的患者相比，来格司亭组患者中性粒细胞减少<0.5×10⁹/L的持续时间显著缩短（中位数分别为18天和22天；P = 0.0005），全血细胞减少<1.0×10⁹/L的持续时间也较短（17天和19天；P = 0.0002），治疗性静脉用抗生素的治疗持续时间减少（20天和24天；P = 0.015），发热>38.0℃的天数有减少趋势（9天和12天；P = 0.18）。两组在血小板恢复、红细胞或血小板输注或非血液学毒性方面无差异。对于首次诱导疗程后达到完全缓解（CR）的患者，来格司亭组观察到开始下一个疗程治疗的时间缩短，从中位数40.5天降至中位数36天（P = 0.082）。化疗的总体完全缓解率相似，来格司亭组为81%，无细胞因子组为75%（P = 0.5），生存时间无显著差异。我们得出结论，在高剂量阿糖胞苷强化诱导治疗AML后，可观察到G-CSF的粒细胞生成刺激作用，这导致一些临床重要参数得到改善，且无重大不良反应。
