Löwenberg B, Suciu S, Archimbaud E, Ossenkoppele G, Verhoef G E, Vellenga E, Wijermans P, Berneman Z, Dekker A W, Stryckmans P, Schouten H, Jehn U, Muus P, Sonneveld P, Dardenne M, Zittoun R
Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Blood. 1997 Oct 15;90(8):2952-61.
We conducted a prospective randomized multicenter clinical trial comparing the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjunct to intensive chemotherapy in patients of 61 years and older with untreated newly diagnosed acute myeloid leukemia (AML). Patients were randomized to either receive daunomycin-cytosine arabinoside with GM-CSF or daunomycin-cytosine arabinoside (control arm). Based on the rationale that GM-CSF might sensitize the leukemic cells to the cytotoxicity of chemotherapy as well as enhance white blood cell regeneration, GM-CSF was given during chemotherapy as well as after chemotherapy. Patients were treated with one, and in case of a partial response, with two remission induction cycles. When a complete remission was attained they received one additional cycle of consolidation therapy. Of 318 evaluable patients with a median age of 68 years, 157 were randomized to receive GM-CSF and 161 were assigned to control therapy. The effect of GM-CSF on treatment was evaluated according to intention-to-treat. Complete remission was achieved in 56% of the patients in the GM-CSF group and 55% of the control patients (P = .98). Recovery of neutrophils was significantly faster in GM-CSF-treated patients. The median time of recovery of neutrophils towards 0.5 x 10(9)/L was 23 days in the GM-CSF group versus 25 days in the control group (P = .0002) with the percentages of patients who recovered being 81% and 71%, respectively. With a median follow-up of 36 months, the probabilities of survival at 2 years after randomization were estimated at 22% for individuals assigned to the GM-CSF treatment as well as for control patients (P = .55). Disease-free survival at 2 years compared 15% and 19% for the two treatment groups (P = .69). The number of nights spent in the hospital, number of transfusions, and frequencies and types of hemorrhages and infections did not differ either. The cytogenetic results at diagnosis of this study in elderly AML shows that there is a relatively high numerical representation of patients with abnormal cytogenetics (55% of documented cases), who showed significantly inferior response rates and survival duration. We conclude that, except for a faster neutrophil recovery, GM-CSF during and after induction chemotherapy does not improve the clinical outcome of elderly patients with AML.
我们进行了一项前瞻性随机多中心临床试验，比较粒细胞巨噬细胞集落刺激因子（GM-CSF）作为辅助治疗对61岁及以上未经治疗的新诊断急性髓系白血病（AML）患者强化化疗效果的影响。患者被随机分为两组，一组接受柔红霉素-阿糖胞苷联合GM-CSF治疗，另一组接受柔红霉素-阿糖胞苷治疗（对照组）。基于GM-CSF可能使白血病细胞对化疗的细胞毒性敏感以及增强白细胞再生的理论依据，GM-CSF在化疗期间和化疗后均给药。患者接受一个诱导缓解周期治疗，若部分缓解则接受两个诱导缓解周期治疗。达到完全缓解后患者再接受一个巩固治疗周期。在318例可评估患者中，中位年龄为68岁，157例随机接受GM-CSF治疗，161例接受对照治疗。根据意向性分析评估GM-CSF对治疗的效果。GM-CSF组56%的患者达到完全缓解，对照组为55%（P = 0.98）。GM-CSF治疗的患者中性粒细胞恢复明显更快。GM-CSF组中性粒细胞恢复至0.5×10⁹/L的中位时间为23天，对照组为25天（P = 0.0002），恢复的患者百分比分别为81%和71%。中位随访36个月，随机分组后2年时GM-CSF治疗组和对照组患者的生存概率估计均为22%（P = 0.55）。两组治疗组2年时的无病生存率分别为15%和19%（P = 0.69）。住院天数、输血次数以及出血和感染的频率及类型也无差异。本研究中老年AML患者诊断时的细胞遗传学结果显示，细胞遗传学异常患者的比例相对较高（记录病例的55%），这些患者的缓解率和生存期明显较差。我们得出结论，除了中性粒细胞恢复更快外，诱导化疗期间及之后使用GM-CSF并不能改善老年AML患者的临床结局。
