欢迎访问《中国临床药理学与治疗学》杂志官方网站,今天是

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (5): 561-569.doi: 10.12092/j.issn.1009-2501.2018.05.014

• 药物治疗学 • 上一篇    下一篇

小剂量高三尖杉酯碱联合全反式维甲酸及三氧化二砷治疗急性早幼粒细胞白血病的临床研究

陈 冬1,陆 滢1,裴仁治1,娄引军2,王敬瀚2,叶佩佩1,张丕胜1,金 洁2   

  1. 1 宁波大学附属鄞州医院血液科,宁波 315040,浙江; 2 浙江大学医学院附属第一医院血液科,杭州 310009,浙江
  • 收稿日期:2018-02-05 修回日期:2018-02-27 出版日期:2018-05-26 发布日期:2018-05-16
  • 通讯作者: 金洁,主任医师,教授,博士生导师,主要从事恶性血液病的基础与临床研究。 Tel:0574-87016871 E-mail:zjyzyycd@126.com
  • 作者简介:陈冬,男,本科,副主任医师,主要从事恶性血液病的基础与临床研究。
  • 基金资助:

    宁波市社发攻关计划项目(2014C50028)

Outcome of acute promyelocytic leukemia treated with low dose homoharringtonine, alltrans retinoic acid and arsenic trioxide

CHEN Dong1, LU Ying1, PEI Renzhi1, LOU Yinjun2, WANG Jinghan2, YE Peipei1, ZHANG Pisheng1, JIN Jie2   

  1. 1 Department of Hematology, Yinzhou Hospital Affiliated to Ningbo University, Ningbo 315040, Zhejiang, China; 2 Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou 310009, Zhejiang, China
  • Received:2018-02-05 Revised:2018-02-27 Online:2018-05-26 Published:2018-05-16

摘要:

目的:观察在初发急性早幼粒细胞白血病(APL)中应用小剂量高三尖杉醋碱(HHT)联合全反式维甲酸(ATRA)以及三氧化二砷(ATO)作为诱导治疗方案的疗效及诱导治疗期间的不良事件发生情况,并与去甲氧柔红霉素(IDA)联合ATRA及ATO的治疗方案进行对比分析。方法:选取了2004年1月至2013年12月期间收治的的145例APL患者的资料进行回顾性分析,其中HHT治疗组74例,IDA治疗组71例,对比分析两组的完全缓解率(CR),总生存率(OS)以及无事件生存率(EFS)及不良反应发生情况。结果:145例患者的CR率为97.2%(141/145),HHT组与IDA组两组的CR率相似(98.6% vs. 95.7%,P=0.36),到达CR时间分别为32.9 d和33.3 d(P=0.645),获得分子生物学缓解时间分别为1.9月和2.2月(P=0.091),无显著统计学差异。有4例患者早期死亡(2.8%),其中3例死于颅内出血,1例死于呼吸窘迫(ARDS)。平均随访45.6月(0.17~131.5月),两组间的OS和EFS均无统计学差异(P=0.9 ,P=0.093)。一共13例患者复发,其中分子生物学复发5例,中枢神经系统复发2例,两组的复发率差异无统计学意义(6.7% vs. 11.2%,P=0.342)。在亚组分析中,无论是中低危还是高危患者中,两组的OS和EFS也没有显示出统计学差异(均P>0.05)。在不良反应方面,HHT组的血液学毒性显著低于IDA组(P=0.003),合并1级发热的患者比例低于IDA组(28.3% vs. 45.1%, P=0.037)。其他肝肾及心脏等重要脏器损害,重要脏器出血等发生率在两组间无统计学差异。结论:ATRA及ATO分别联合小剂量HHT和IDA的方案在初治APL患者中的疗效近似,但联合小剂量HHT组的血液学毒性更小,相应的感染发生率更低。

关键词: 白血病, 早幼粒细胞, 急性, 高三尖酯碱, 预后

Abstract:

AIM: To investigate the complete remssion(CR),overall survival(OS),event free survival(EFS)and adverse events of newly diagnosised acute promyelocytic leukemia (APL) treated with low dose homoharringtonine(HHT), alltrans retinoic acid(ATRA) and arsenic trioxide(ATO), and to evaluate the efficacy treatment outcome by comparing HHT,ATRA and ATO with idarubicin(IDA), ATRA and ATO.  METHODS: A total of 145 cases (74 in HHT group, 71 in IDA group) of newly diagnosed acute promyelocytic leukemia from January 2004 to December 2013 in The First affiliated hospital of Zhejiang University School of Medicine and Yinzhou Hospital Affiliated to Ningbo University were analyzed, and were enrolled in the analyses of clinical feature, molecular biology,OS and EFS after long term follow up.RESULTS:The overall CR of 145 pations was 97.2%(141/145), the CR rate of  HTT group and IDA group was similar(98.6% vs. 95.7%,P=0.36). The interval to achieve hematological CR in two group was 32.89 and 33.3 days,the converting to PML/RARa PCR-negative from the induction therapy was 1.9 and 2.17 months respectively, similarly, there were no significant difference between the two groups (P=0.645 and 0.091, respectively). Four patients occurred early death (2.8%), 3 cases died of intracranial hemorrhage, 1 case died of respiratory distress (ARDS). With a median follow-up of 45.6 months, the two groups did not differ between the OS and EFS (P=0.9 and 0.093). A total of 13 patients relapse, including 5 cases of recurrence of molecular biology, the central nervous system relapse in 2 cases, there was no statistically significant difference of recurrence rates in the two groups (6.7% vs. 11.2%, P=0.342). And the risk group was not the factor affecting OS and EFS (P>0.05).While the incidence of hematology toxicity and grade 1 fever in HTT group were significantly lower than IDA group (P=0.003 and 0.037). And no difference was found in terms of liver dysfunction,renal dysfunction,cardiac dysfunction,and visceral bleeding, etc between two groups. CONCLUSION: Our study demonstrated comparable therapeutic effect of low dose HHT or IDA on APL,HHT was also well tolerated and had lower hematology toxicity and infection rate.

Key words: leukemia, promyelocytic, acute, trichothecenes, prognosis

中图分类号: