Maladies du sang, CHU INSERM U892, 4 rue Larrey, 49000 Angers, France.
Haematologica. 2011 Feb;96(2):245-52. doi: 10.3324/haematol.2010.027862. Epub 2010 Oct 22.
The prognosis of acute lymphoblastic leukemia in the elderly is poor. The GRAALL-SA1 phase II, randomized trial compared the efficacy and toxicity of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in patients 55 years or older with Philadelphia chromosome-negative acute lymphoblastic leukemia.
Sixty patients received either continuous-infusion doxorubicin (12 mg/m(2)/day) and continuous-infusion vincristine (0.4 mg/day) on days 1-4 or pegylated liposomal doxorubicin (40 mg/m(2)) and standard vincristine (2 mg) on day 1, accompanied by dexamethasone, followed at day 28 by a second cycle, reinforced by cyclophosphamide. End-points were safety, outcome and prognostic factors.
Myelosuppression was reduced in the pegylated liposomal doxorubicin arm with shorter severe neutropenia (P=0.05), shorter severe thrombocytopenia (P=0.03), and fewer red blood cell transfusions (P=0.04). Grade 3/4 infections and Gram-negative bacteremia were reduced in the pegylated liposomal doxorubicin arm (P=0.04 and P=0.02, respectively). There was a trend towards fewer cardiac events among the patients who received pegylated liposomal doxorubicin (1/29 versus 6/31). The complete remission rate was 82% and, with a median follow-up of 4 years, median event-free survival and overall survival were 9 and 10 months, respectively. Despite the better tolerance of pegylated liposomal doxorubicin, no differences in survival were observed between the two arms, due to trends towards more induction refractoriness (17 versus 3%, P=0.10) and a higher cumulative incidence of relapse (52% versus 32% at 2 years, P=0.20) in the pegylated liposomal doxorubicin arm.
With the drug schedules used in this study, pegylated liposomal doxorubicin did not improve the outcome of elderly patients with acute lymphoblastic leukemia despite reduced toxicities.
老年人急性淋巴细胞白血病的预后较差。GRAALL-SA1 期、随机试验比较了培美曲塞脂质体阿霉素与连续输注阿霉素在费城染色体阴性急性淋巴细胞白血病、55 岁或以上患者中的疗效和毒性。
60 例患者接受连续输注阿霉素（12mg/m²/天）和连续输注长春新碱（0.4mg/天），第 1-4 天或培美曲塞脂质体阿霉素（40mg/m²）和标准长春新碱（2mg），第 1 天，同时给予地塞米松，第 28 天进行第二个周期，用环磷酰胺强化。终点是安全性、结果和预后因素。
培美曲塞脂质体阿霉素组骨髓抑制减少，严重中性粒细胞减少症（P=0.05）、严重血小板减少症（P=0.03）和红细胞输注减少（P=0.04）时间缩短。培美曲塞脂质体阿霉素组 3/4 级感染和革兰氏阴性菌血症减少（P=0.04 和 P=0.02）。培美曲塞脂质体阿霉素组心脏事件发生率呈下降趋势（1/29 例与 6/31 例）。完全缓解率为 82%，中位随访 4 年后，中位无事件生存和总生存时间分别为 9 个月和 10 个月。尽管培美曲塞脂质体阿霉素耐受性较好，但两组间生存无差异，主要是因为诱导耐药性趋势较高（17%比 3%，P=0.10）和培美曲塞脂质体阿霉素组累积复发率较高（2 年时为 52%比 32%，P=0.20）。
在本研究中使用的药物方案中，培美曲塞脂质体阿霉素并未改善老年急性淋巴细胞白血病患者的预后，尽管毒性降低。
