维甲酸、亚砷酸联合蒽环类药物三药诱导方案对成人非高危急性早幼粒细胞白血病的疗效分析

Effect of triple-induction regimen including all-trans retinoic acid, arsenic trioxide plus anthracyclines for adults with non-high-risk acute promyelocytic leukemia

目的分析全反式维甲酸(ATRA)、三氧化二砷(ATO)联合蒽环类药物三药诱导方案与ATRA+ATO双诱导方案对成人非高危急性早幼粒细胞白血病(APL)的疗效。方法回顾性分析2009年1月至2019年12月在河南省人民医院首次确诊并治疗的成人非高危APL患者的临床资料。患者根据治疗方案分为三药组及双药组,收集两组的一般资料、诱导期间的血常规、凝血功能变化、输血情况等,并分析两组的完全缓解率、早期死亡率及预后。结果共纳入164例患者,其中男86例、女78例;年龄的M(Q1,Q3)为41(18,70)岁;其中三药组75例、双药组89例。三药组在治疗的第7天和第14天白细胞(WBC)计数分别为(9.49±6.10)×10^(9)/L、(5.43±3.97)×10^(9)/L,双药组为(15.17±17.06)×10^(9)/L、(13.37±12.59)×10^(9)/L,差异均有统计学意义(均P<0.05);且三药组WBC峰值低于双药组[13.8(6.3,89.7)×10^(9)/L比19.2(3.8,112.8)×10^(9)/L,P=0.019]。诱导治疗第7天,三药组患者血小板(PLT)计数低于双药组[27(11,147)×10^(9)/L比45(8,183)×10^(9)/L,P=0.014];但第14、21、28天两组PLT差异无统计学意义,诱导治疗期间两组患者输注PLT的量差异也无统计学意义(均P>0.05)。治疗前后,两组仅有极少患者凝血酶原时间(PT)延长≥3 s和(或)活化部分凝血活酶时间(APTT)延长≥10 s,且差异均无统计学意义(均P>0.05)。三药组患者诱导分化综合征的发生率低于双药组(2.7%比12.4%,P=0.022);早期死亡率虽低于双药组(1.3%比5.6%),但差异无统计学意义(P>0.05);两组早期完全缓解率、遗传学缓解率、分子学缓解率、复发率、总生存率及无病生存率差异均无统计学意义。结论对于成人非高危APL患者,三药诱导方案可降低WBC计数和峰值,减少诱导分化综合征的发生率。

Objective To analyze the effect of triple-induction regimen including all-trans retinoic acid(ATRA),arsenic trioxide(ATO)plus anthracyclines and double-induction regimen including ATRA and ATO for adults with non-high-risk acute promyelocytic leukemia(APL).Methods The clinical data of adult patients with non-high-risk APL who were first diagnosed and admitted to the Henan Provincial People′s Hospital from January 2009 to December 2019 were retrospectively analyzed.All patients were divided into triple-induction group and double-induction group according to the treatment.The general data of patients,blood routine,coagulation function changes and blood transfusions during the induction period were collected,and the complete remission rate,early mortality and prognosis of two groups were analyzed.Results A total of 164 patients were enrolled,including 86 males and 78 females,and the M(Q1,Q3)of their age was 41(18,70)years.Among them,75 were in triple-induction group and 89 in double-induction group.The white blood cell(WBC)counts of triple-induction group on day 7th and 14th after induction were(9.49±6.10)×10^(9)/L and(5.43±3.97)×10^(9)/L,while those in double-induction group were(15.17±17.06)×10^(9)/L and(13.37±12.59)×10^(9)/L,the differences were statistically significant(both P<0.05).In addition,the peak of WBC in the triple-induction group was lower than that in the double-induction group[13.8(6.3,89.7)×10^(9)/L vs 19.2(3.8,112.8)×10^(9)/L,P=0.019].On day 7th after induction,the platelet(PLT)counts in the triple-induction group was lower than that in the double-induction group[27(11,147)×10^(9)/L vs 45(8,183)×10^(9)/L,P=0.014].However,the difference was not statistically significant in PLT counts between the two groups on day 14th,21st and 28th,or in PLT transfusions during induction(all P>0.05).After treatment,it was observed only in a few patients of two groups that the prothrombin time(PT)elongation≥3 s and/or activated partial thromboplastin time(APTT)elongation≥10 s,and the difference was not statistically significant(all P>0.05).The incidence of induced differentiation syndrome in the triple-induction group was lower than that in the double-induction group(2.7%vs 12.4%,P=0.022)The early mortality rate was lower than that in the double-induction group(1.3%vs 5.6%),but the difference was not statistically significant(P>0.05).There were no statistically significant differences in the early complete remission rate,genetic remission rate,molecular remission rate,relapse rate,overall survival(OS)rate and disease-free survival(DFS)rate between the two groups.Conclusion For adults with non-high-risk APL,the triple-induction therapy can reduce the counts and peaks of WBC,and reduce the incidence of induced differentiation syndrome.