High-Dose Cytarabine Consolidation With or Without Additional Amsacrine and Mitoxantrone in Acute Myeloid Leukemia: Results of the Prospective Randomized AML2003 Trial
High-Dose Cytarabine Consolidation With or Without Additional Amsacrine and Mitoxantrone in Acute Myeloid Leukemia: Results of the Prospective Randomized AML2003 Trial
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DOI：
10.1200/jco.2012.46.4743
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发表时间：
2013-06-10
影响因子：
45.3
通讯作者：
Ehninger, Gerhard
中科院分区：
文献类型：
--
作者：
Schaich, Markus;Parmentier, Stefani;Ehninger, Gerhard
目的在一项前瞻性、随机、多中心试验中评估多药巩固治疗急性髓性白血病（AML）的疗效。患者和方法在2003年12月至2009年11月期间，1179例未经治疗的AML患者（中位年龄48岁，范围16至60岁）在诊断时被随机分配接受标准高剂量阿糖胞苷巩固治疗，3个周期18 g/m(2) (3x HD-AraC)，或多药物巩固治疗，2个周期米托蒽醌（30 mg/m(2)）加阿糖胞苷（12 g/m(2)）和1个周期阿糖胞苷（500 mg/m(2)）加阿糖胞苷（10 g/m(2)）；MAC / MAMAC / MAC)。同种异体和自体造血干细胞移植以风险适应和优先级为基础的方式进行。结果采用标准剂量阿糖胞苷和柔红霉素3 + 7双诱导治疗方案后，65%的患者完全缓解。在可评估巩固结果的主要疗效人群中，根据意向治疗分析，使用3x HD-AraC或MAC/MAMC/MAC进行巩固治疗在3年总体（69% vs 64%; P = 0.18）或无病生存（46% vs 48%; P = 0.99）方面没有任何显著差异。此外，MAC/MAMAC/MAC导致额外的胃肠道和肝脏毒性以及更高的感染和出血率，导致在按方案分析中，与3x HD-AraC相比，3年总生存期明显缩短（63% vs 72%; P = 0.04）。结论：在年轻AML患者中，米托蒽醌和阿沙林联合大剂量阿糖胞苷的多药巩固治疗并不能改善治疗结果，而且会带来额外的毒性。(C)美国临床肿瘤学会2013
PurposeTo assess the treatment outcome benefit of multiagent consolidation in young adults with acute myeloid leukemia (AML) in a prospective, randomized, multicenter trial.Patients and MethodsBetween December 2003 and November 2009, 1,179 patients (median age, 48 years; range, 16 to 60 years) with untreated AML were randomly assigned at diagnosis to receive either standard high-dose cytarabine consolidation with three cycles of 18 g/m(2) (3x HD-AraC) or multiagent consolidation with two cycles of mitoxantrone (30 mg/m(2)) plus cytarabine (12 g/m(2)) and one cycle of amsacrine (500 mg/m(2)) plus cytarabine (10 g/m(2); MAC/MAMAC/MAC). Allogeneic and autologous hematopoietic stem-cell transplantations were performed in a risk-adapted and priority-based manner.ResultsAfter double induction therapy using a 3 + 7 regimen including standard-dose cytarabine and daunorubicin, complete remission was achieved in 65% of patients. In the primary efficacy population of patients evaluable for consolidation outcomes, consolidation with either 3x HD-AraC or MAC/MAMC/MAC did not result in any significant difference in 3-year overall (69% v 64%; P = .18) or disease-free survival (46% v 48%; P = .99) according to the intention-to-treat analysis. Furthermore, MAC/MAMAC/MAC led to additional GI and hepatic toxicity and a higher rate of infection and bleeding, resulting in significantly shorter 3-year overall survival in the per-protocol analysis compared with 3x HD-AraC (63% v 72%; P = .04).ConclusionIn younger adults with AML, multiagent consolidation using mitoxantrone and amsacrine in combination with high-dose cytarabine does not improve treatment outcome and confers additional toxicity. (C) 2013 by American Society of Clinical Oncology