不同剂量伊达比星联合阿糖胞苷对60岁以下成人急性髓系白血病诱导疗效的临床研究

A Clinical Study on the Induction Effect of Different doses of Idarubicin Combined with Cytarabine on Acute Myeloid Leukemia in Adults Under 60 Years of Age

目的探讨不同剂量的蒽环类药物伊达比星(IDA)对于60岁以下成人急性髓系白血病(AML)患者诱导治疗的临床疗效。方法从2015年6月~2019年12月,本中心共诊断265例年轻(14~59岁)AML患者,回顾性分析了239例使用伊达比星联合阿糖胞苷(IA 3+7)方案诱导治疗的患者,重点关注完全缓解(CR)率、复发以及不同预后风险组患者的长期生存。结果在接受首次诱导治疗后,IDA 8 mg/m^(2)组和IDA 10~12 mg/m^(2)组分别有61例(65.6%)和103例(70.6%)患者获得形态CR(P=0.475),其中IDA 8 mg/m^(2)组26例(42.6%)患者微小残留病灶(MRD)转阴,IDA 10~12 mg/m^(2)组64例(62.1%)患者MRD转阴(P=0.048)。IDA 8 mg/m^(2)组和IDA 10~12 mg/m^(2)组3年疾病累积复发率分别为45.1%(95%CI:34.1%~57.8%)和49.6%(95%CI:40.7%~59.3%)(P=0.469)。IDA 8 mg/m^(2)组3年总生存(OS)率为34.6%(95%CI:24.9%~44.4%)明显低于IDA 10~12 mg/m^(2)组46.6%(95%CI:38.2%~54.6%)(P=0.038);其中预后中等组IDA 8 mg/m^(2)组3年OS率为31.5%(95%CI:18.9%~45.0%),明显低于IDA 10~12 mg/m^(2)组的为43.7%(95%CI:32.3%~54.6%)(P=0.043)。3年无事件生存(EFS)率IDA 8 mg/m^(2)组和IDA 10~12 mg/m^(2)组分别为32.0%(95%CI:22.7%~41.6%)和37.0%(95%CI:29.2%~44.8%)(P=0.319);其中预后中等组IDA 8 mg/m^(2)组为25.4%(95%CI:14.0%~38.4%)稍低于IDA 10~12 mg/m^(2)组33.3%(95%CI:23.0%~44.0%)(P=0.107)。3年OS率和3年EFS率无论在预后良好组还是在预后不良组均未见明显差异。结论对于年轻成人AML患者,特别是对于2017ELN风险分层为预后中等的患者,使用伊达比星10~12 mg•m^(-2)•d^(-1)×3 d为基础的IA(3+7)方案诱导治疗能够获得更高的免疫学缓解和更好地长期生存。

Objective To investigate the clinical efficacy of different doses of anthracycline idarubicin in the induction treatment of acute myeloid leukemia(AML)for adults aged less than 60.Methods A total of 265 young AML patients(14~59 years old)were diagnosed at our center from June 2015 to December 2019.We retrospectively reviewed 239 patients treated with the regimen of idarubicin combined with cytarabine(IA 3+7),focusing on complete remission(CR)rate,recurrence and long-term survival in patients with different prognostic risk groups.Results After the first induction therapy,61(65.6%)and 103(70.6%)patients in the IDA 8 mg/m^(2) group and the IDA 10~12 mg/m^(2) group obtained morphological CR(P=0.475),of which 26 patients(42.6%)in the IDA 8 mg/m^(2) group and 64 patients(62.1%)in the IDA 10~12 mg/m^(2) group had minimal residual disease(MRD)negativity.The 3-year cumulative incidence of relapse(CIR)was 45.1%(95%CI:34.1%~57.8%)in the IDA 8 mg/m^(2) group and 49.6%(95%CI:40.7%~59.3%)in the IDA 10~12 mg/m^(2) group(P=0.469).The 3-year overall survival(OS)rate was lower in the IDA 8 mg/m^(2) group[34.6%(95%CI:24.9%~44.4%)]than in the IDA 10~12 mg/m^(2) group[46.6%(95%CI:38.2%~54.6%)](P=0.038).For intermediate-risk patients,the 3-year OS rate for patients in the IDA 8 mg/m^(2) group was 31.5%(95%CI:18.9%~45.0%),which was significantly lower than that in the IDA 10~12 mg/m^(2) group[43.7%(95%CI:32.3%~54.6%)](P=0.043).The 3-year event-free survival(EFS)rate in the IDA 8 mg/m^(2) group and the IDA 10~12 mg/m^(2) group were 32.0%(95%CI:22.7%~41.6%)and 37.0%(95%CI:29.2%~44.8%)respectively(P=0.319).For intermediate-risk patients,there was a lower trend of the 3-year EFS rate in the IDA 8 mg/m^(2) group[25.4%(95%CI:14.0%~38.4%)]than in the IDA 10~12 mg/m^(2) group[33.3%(95%CI:23.0%~44.0%)](P=0.107).There were no significant differences in the 3-year OS rate and 3-year EFS rate between the favourable risk group and the adverse risk group.Conclusion For young adult patients with AML,the induction therapy with IA(3+7)regimen based on idarubicin 10~12 mg•m^(-2)•d^(-1)×3 d could achieve higher immunological remission and better long-term survival,especially for patients with intermediate risk according to 2017 ELN risk stratification.