Xu Shuang-nian, Chen Jie-ping, Liu Jian-ping, Xia Yun
Center for Hematology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Zhong Xi Yi Jie He Xue Bao. 2009 Sep;7(9):801-8. doi: 10.3736/jcim20090901.
To systematically review the efficacy and safety of arsenic trioxide (ATO) in treatment of acute promyelocytic leukemia (APL).
The Cochrane Library (Issue 1, 2009), Cochrane Central Register of Controlled Trials (from 1970 to January 2009), MEDLINE (from 1978 to October 2008), EMBASE (from 1950 to March 2009), Chinese Biological Medical Literature Database (from 1978 to December 2008), China National Knowledge Infrastructure (CNKI, from 1994 to December 2008), and China Medical Academic Conference Database (from 1994 to December 2008) were electronically searched. We also searched the Meta-Register of controlled trials, Conference Proceedings of American Society of Hematology (from 1946 to December 2008) and Conference Proceedings of American Society of Clinical Oncology (from 1946 to December 2008) on the internet for grey literature. The related journals in the library of Third Military Medical University were hand-searched. The randomized controlled trials (RCTs) of ATO in treatment of APL were included. We adopted complete remission, overall survival rate, disease free survival rate, time to complete remission, relapse rate, mortality and adverse reactions as outcome indicators. Data were entered and analyzed with the Cochrane review manager software 5.0 (RevMan 5.0).
After merger of the included trials, five eligible RCTs with 328 cases were included. All the RCTs focused on the comparison of all-trans retinoic acid (ATRA) plus ATO regimen with ATRA monotherapy. Meta-analysis showed that the effect indexes for time to complete remission, two-year disease free survival rate, relapse rate, incidence of edema and incidence rate of QT interval prolongation were -1.20 [-1.68, -0.72], 8.64 [1.66,45.00], 0.21 [0.09,0.47], 4.16 [1.46,11.79] and 22.10 [2.75,177.49], respectively. The influences on other outcome indicators such as complete remission and leukocytosis were statistically non-significant.
ATO can prolong disease free survival and reduce the time to complete remission and relapse rate of newly diagnosed APL patients, and increase the incidence of edema and prolongation of corrected QT interval during the treatment. Due to limitation of the included trials, this conclusion needs to be validated by further studies.
系统评价三氧化二砷（ATO）治疗急性早幼粒细胞白血病（APL）的疗效和安全性。
电子检索Cochrane图书馆（2009年第1期）、Cochrane对照试验中心注册库（1970年至2009年1月）、MEDLINE（1978年至2008年10月）、EMBASE（1950年至2009年3月）、中国生物医学文献数据库（1978年至2008年12月）、中国知网（CNKI，1994年至2008年12月）以及中国医学学术会议数据库（1994年至2008年12月）。同时在互联网上检索对照试验的Meta注册库、美国血液学会会议论文集（1946年至2008年12月）以及美国临床肿瘤学会会议论文集（1946年至2008年12月）以获取灰色文献。手工检索第三军医大学图书馆的相关期刊。纳入ATO治疗APL的随机对照试验（RCT）。采用完全缓解率、总生存率、无病生存率、完全缓解时间、复发率、死亡率及不良反应作为观察指标。数据采用Cochrane系统评价管理软件5.0（RevMan 5.0）进行录入和分析。
纳入试验合并后，共纳入5项合格的RCT，328例患者。所有RCT均聚焦于全反式维甲酸（ATRA）联合ATO方案与ATRA单药治疗的比较。Meta分析显示，完全缓解时间、两年无病生存率、复发率、水肿发生率及QT间期延长发生率的效应指标分别为-1.20[-1.68，-0.72]、8.64[1.66，45.00]、0.21[0.09，0.47]、4.16[1.46，11.79]和22.10[2.75，177.49]。对其他观察指标如完全缓解和白细胞增多的影响无统计学意义。
ATO可延长新诊断APL患者的无病生存期，缩短完全缓解时间并降低复发率，但治疗期间水肿发生率增加，校正QT间期延长。由于纳入试验的局限性，该结论需进一步研究验证。
