摘要目的 探讨含不同剂量去甲氧柔红霉素(IDA 8、10、12 mg/m2)的IA方案诱导治疗成人初发急性髓系白血病(AML)(非急性早幼粒细胞白血病)的临床疗效和安全性.方法 采用多中心、单盲、非随机、临床对照研究,纳入2011年5月至2015年3月苏州大学附属第一医院及其他36家单位收治的1 215例成人初发AML患者,根据诱导化疗方案中IDA的剂量对患者进行分组,分析不同剂量IDA联合阿糖胞苷(100 mg/m2)组成的IA方案在成人初发AML诱导治疗中的完全缓解(CR)率、血液学及非血液学不良事件.结果 可纳入缓解率分析的AML患者共1 207例,IDA 8 mg/m2、10 mg/m2和12 mg/m2组的CR率分别为73.6％(215/292)、84.1％ (662/787)和86.7％(111/128),差异有统计学意义(P＜0.001);以IDA 8 mg/m2组为参照组,在调整了年龄、骨髓原始细胞比例、FAB分型、危险度分层后,IDA 10 mg/m2和IDA 12 mg/m2为影响患者CR的有利因素[OR=0.49 (95％ CI 0.34～ 0.70),P＜0.001;OR=0.36(95％CI 0.18 ～ 0.71),P=0.003].在中、低危组中三组CR率分别为76.5％(163/213)、86.9％ (506/582)和86.1％(68/79),差异有统计学意义(P=0.007);在调整了年龄、骨髓原始细胞比例、FAB分型因素后,IDA 10 mg/m2为影响患者CR的有利因素[OR=0.47 (95％ CI 0.31 ～ 0.71),P＜0.001].在高危组中,三组CR率分别为50.0％(18/36)、60.6％(43/71)和81.8％(18/22),差异无统计学意义(P=0.089),但在调整了年龄、骨髓原始细胞比例、FAB分型因素后,IDA 12 mg/m2为影响患者CR的有利因素[OR=0.22(95％ CI 0.06～ 0.80),P=0.022].8 mg/m2、10 mg/m2和12 mg/m2组中性粒细胞≤0.5×109/L的中位持续时间分别为14(11～ 18)、15(11～ 20)和18(14～ 22)d,差异有统计学意义(P=0.012);三组PLT≤20×109/L的中位持续时间分别为14(7～17)、15(11～ 20)和17(15～21)d,差异有统计学意义(P=0.001);三组肺部感染发生率分别为9.8％、13.5％和25.2％,差异有统计学意义(P＜0.001).结论 在中国成人(18 ～ 60岁)初发AML中,建议中、低危组患者采用含IDA10mg/m2的IA方案进行诱导治疗;而高危组AML建议选择含IDA12mg/m2的IA方案进行诱导治疗.

abstractsObjective To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m2,10 mg/m2 or 12 mg/m2 as induction chemotherapy for adult patients with denovo acute myeloid leukemia (AML).Methods A total of 1 215 newly diagnosed adult AML patients,ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multi-center,single-blind,non-randomized,clinical controlled study.To compare the response rate of complete remission (CR),adverse events between different dose idarubicin combined with cytarabine (100 mg/m2) as induction chemotherapy in newly diagnosed patients of adult AML.Results Of 1 207 evaluable AML patients were assigned to this analysis of CR rate.The CR rates of IDA 8 mg/m2 group,IDA 10 mg/m2 group and IDA 12 mg/m2 group were 73.6％ (215/292),84.1％ (662/787) and 86.7％ (111/128),respectively (P ＜ 0.001).After adjusted for age,blast ratio of bone marrow,FAB classification and risk stratification,the odds ratios (95％ CI) of IDA 10 mg/m2 group and IDA 12 mg/m2 group were 0.49 (0.34-0.70) and 0.36(0.18-0.71),as compared with the IDA 8 mg/m2 group (P＜ 0.001,P=0.003).In the intermediate and favorable groups,CR rates was 76.5％ (163/213),86.9％ (506/582) and 86.1％ (68/79) in different doses of IDA (P=0.007).Interestingly,IA regimen with IDA 10 mg/m2 was the only beneficial factor affecting CR in this group after adjusted for age,blast ratio of bone marrow and FAB classification [OR =0.47 (95％ CI 0.31-0.71),P ＜0.001].CR rates in adverse group was 50.0％ (18/36),60.6％ (43/71) and 81.8％ (18/22) respectively (P=0.089).However,the odds ratios (95％ CI) of IDA 12 mg/m2 when compared with the IDA 8 mg/m2 was 0.22(0.06-0.80),after adjusted for age,blast ratio of bone marrow and FAB classification.The median time (days) of neutrophil count less than 0.5 × 109/L in IDA 8 mg/m2 group,IDA 10 mg/m2 group and IDA 12 mg/m2 group were 14 (11-18),15 (11-20) and 18 (14-22),respectively (P =0.012) and of platelet count lower than 20 × 109/L were 14 (7-17),15 (11-20) and 17 (15-21),respectively (P =0.001).The incidences of lung infection in the three groups were 9.8％,13.5％ and 25.2％,respectively (P ＜ 0.001).Conclusions For young adult patients (aged 18-60 years) with AML in China,intensifying induction therapy with idarubicin 10 mg/m2 is clinically superior to IDA 8 mg/m2 and IDA 12 mg/m2 in favorable intermediate AML subgroup.However,idarubicin 12 mg/m2 is more suitable to adverse AML subgroup.