亚砷酸治疗急性早幼粒细胞白血病致QT间期延长的发生率及影响因素

摘要

目的 分析应用亚砷酸(ATO)治疗急性早幼粒细胞白血病(APL)过程中患者校正的QT间期(QTc)延长的发生率及发生时相以及相关因素,从而探索降低或避免ATO致心脏事件的方法.方法 回顾性分析2006年5月至2017年2月大连医科大学附属第一医院血液科接受ATO治疗资料完整的APL患者,全部病例均符合白血病MICM分型标准,即细胞形态学(morphology)、免疫学(immunolo-gy)、细胞遗传学(cytogenetics)和分子生物学(molecular biology)分型,ATO剂量为0.16 mg·kg-1·d-1,诱导、复发后再诱导应用ATO中位时间28 d,巩固治疗每疗程14 d.收集患者的基本信息、生化指标及心电图数据进行统计学分析,对比用药前后参数变化.结果 入组患者61例,男36例、女25例,中位年龄44岁,中位治疗次数11次,诱导治疗及复发后再诱导治疗82次,巩固治疗170次.根据诱导治疗前白细胞、血小板水平进行危险分层,将患者分为高危组20例,中危组27例,低危组14例.接受ATO治疗中QTc延长发生率23.8％,QTc较用药前延长(20.38+7.11)ms,差异具有统计学意义(P＜0.05).血红蛋白(HB)≥90 g/L患者QTc延长发生率为21.3％,HB＜90 g/L患者QTc延长发生率为35.1％.诱导治疗中HB＜90 g/L发生率59.7％,QTc延长发生率46.3％,巩固治疗中HB＜90 g/L发生率4.7％,QTc延长发生率为12.9％.乳酸脱氢酶(LDH)正常患者QTc延长发生率为21.4％,LDH升高患者QTc延长发生率为42.9％.用药前心室率与QTc具有相关性,相关系数为0.152,P=0.015,用药后心室率仍与QTc具有相关性,相关系数0.230,P=0.000.结论 应用ATO治疗APL,中重度贫血患者更易出现QTc延长,在诱导治疗期间此现象更为突出;LDH水平升高者QTc延长发生率高;用药期间心室率与QTc具有相关性,通过降低心室率可控制QTc延长.%Objective To analyze the incidence rate and time phases of corrected-QT interval(QTc) prolongation and to explore relevant factors which lead to QTc prolongation during acute promyelocytic leukemia (APL) treatments.Method A retrospective analysis of APL patients who received arsenic trioxide (ATO)standard treatments with complete data in the Hematology Department of the First Hospital of Dalian Medical University from May 2006 to Feb.2017 was conducted.The basic information,biochemical indicators and electrocardiogram data of patients were collected and analyzed statistically.Results Sixty-one patients received 252 times ATO treatments.The incidence rate of QTc prolongation in the treatments was 23.8％ and QTc prolonged (20.38+7.11) ms after drug use(P＜0.05).The QTc prolongation incidence rate was 21.3％ in the patients with hemoglobin(HB) ＞90 g/L,compared with 35.1％ in patients with HB＜90 g/L.In the induction and consolidation therapies,the incidence rate of HB＜90 g/L was 59.7％ and 4.7％,with QTc prolongation incidence rate 46.3％ and 12.9％,respectively.The QTc prolongation incidence rate was 21.4％ in the patients with normal level lactate dehydrogenase (LDH),compared with 42.9％ in the patients with higher-level LDH.The ventricular rate before drug-use had correlation with QTc,the correlation coefficient was 0.152(P=0.015).The ventricular rate after drug use still had correlation with QTc,the correlation coefficient was 0.230 (P =0.000).Conclusion When using ATO,moderate-severe anemia patients were more prone to QTc prolongation.This phenomenon was more prominent during the induction of therapy.High-level LDH patients were with high QTc prolongation incidence rate.The ventricular rate was correlated with QTc during medication.QTc prolongation could be controlled by lowering the ventricular rate.