地西他滨联合CAG治疗中、高危骨髓增生异常综合征及急性髓系白血病的疗效与安全性的Meta分析
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摘要
目的:系统评价地西他滨联合CAG方案(DCAG方案)治疗中、高危MDS及AML的临床疗效及安全性。方法:计算机检索PubMed、EMbase、The Cochrane Library、WanFang Data和CNKI等数据库,搜集DCAG方案对比地西他滨单药方案或CAG方案治疗中、高危MDS及AML的随机对照试验(RCT),检索时限从建库至2018年3月。所纳入RCT依据Cochrane风险偏倚评价工具进行质量评价,采用RevMan 5.3进行Meta分析,结果共纳入24个RCT,包括1 557例中、高危MDS及AML患者,其中594名为AML患者,590名为MDS患者。采用DCAG方案治疗的列入DCAG组,采用地西他滨单药方案或CAG方案治疗的列入对照组。结果:Meta分析结果显示:与对照组比较,DCAG方案治疗中、高危MDS及AML患者的完全缓解率高(RR=1.63,95%CI=1.43-1.85,P<0.000 01),总体有效率也高(RR=1. 35,95%CI=1.24-1.46,P<0.000 01);亚组分析结果显示,在完全缓解率方面DCAG方案好于CAG方案(RR=1.71,95%CI=1.49-1.97,P<0.000 01),稍好于地西他滨单药方案(RR=1.43,95%CI=1.08-1.91,P=0.01)。在不良反应方面,两组的肺部感染、消化道反应、骨髓抑制、出血事件发生率等方面无统计学差异(P>0. 05)。结论:DCAG方案治疗中、高危MDS及AML具有切实而显著的疗效,且优于CAG方案和地西他滨单药方案,两者不良反应事件发生无统计学差异。由于缺乏大样本RCT的支持,上述结论尚待更多高质量研究予以验证。
Objective: To systematically evaluate the efficacy and safety of DCAG regimen for treating the intermediate or high risk MDS and AML. Methods: PubMed, EMbase, The Cochrane Library, WanFang Data and CNKI databases were searched to collect randomized controlled trials(RCTs) of decitabine combined with CAG regimen for intermediate or high risk MDS and AML from inception to March, 2018. The quality of each RCT was evaluated by the Cochrane collaboration′s tool for assessing the risk of bias.Then, the data were analyzed by using RevMan 5.3. Results:Twenty-four RCTs were included in the meta-analysis, containing 1 557 patients with intermediate or high-risk MDS and AML, of whom 594 were AML patients and 590 were MDS patients. The patients treated with the DCAG regimen were enrolled in DCAG group, and the patients treated with single-agent decitabine or CAG regimen were enrolled in control group. Results: The results of meta-analysis showed that compared with other therapies, the complete remission rate of DCAG regimen in patients with intermediate or high-risk MDS and AML was high(RR=1.63,95% CI=1.43-1.85,P<0.000 01), and the overall response rate was also high(RR=1. 35,95% CI=1.24-1.46,P<0.000 01);Subgroup analysis results showed that DCAG regimen was better than CAG regimen in the complete remission rate(RR=1.71,95% CI=1.49-1.97,P<0.000 01), and slightly better than single-agent decitabine group(RR=1.43,95%CI=1.08-1.91,P=0.01). In terms of adverse reactions, there was no statistically significant difference in the rates of myelosuppression, pulmonary infection, gastrointestinal reactions, and bleeding events between the 2 groups(P >0.05).Conclusion: DCAG regimen has significant efficacy in the treatment of intermediate or high-risk MDS and AML, and is superior to CAG regimen and single-agent dicitabine regimen. As compared with control group, there was no significant difference in adverse events. Due to limited quantity and quality of the included studies, more high quality studies are needed to verify above mentioned conclusion.
Objective: To systematically evaluate the efficacy and safety of DCAG regimen for treating the intermediate or high risk MDS and AML. Methods: PubMed, EMbase, The Cochrane Library, WanFang Data and CNKI databases were searched to collect randomized controlled trials(RCTs) of decitabine combined with CAG regimen for intermediate or high risk MDS and AML from inception to March, 2018. The quality of each RCT was evaluated by the Cochrane collaboration′s tool for assessing the risk of bias.Then, the data were analyzed by using RevMan 5.3. Results:Twenty-four RCTs were included in the meta-analysis, containing 1 557 patients with intermediate or high-risk MDS and AML, of whom 594 were AML patients and 590 were MDS patients. The patients treated with the DCAG regimen were enrolled in DCAG group, and the patients treated with single-agent decitabine or CAG regimen were enrolled in control group. Results: The results of meta-analysis showed that compared with other therapies, the complete remission rate of DCAG regimen in patients with intermediate or high-risk MDS and AML was high(RR=1.63,95% CI=1.43-1.85,P<0.000 01), and the overall response rate was also high(RR=1. 35,95% CI=1.24-1.46,P<0.000 01);Subgroup analysis results showed that DCAG regimen was better than CAG regimen in the complete remission rate(RR=1.71,95% CI=1.49-1.97,P<0.000 01), and slightly better than single-agent decitabine group(RR=1.43,95%CI=1.08-1.91,P=0.01). In terms of adverse reactions, there was no statistically significant difference in the rates of myelosuppression, pulmonary infection, gastrointestinal reactions, and bleeding events between the 2 groups(P >0.05).Conclusion: DCAG regimen has significant efficacy in the treatment of intermediate or high-risk MDS and AML, and is superior to CAG regimen and single-agent dicitabine regimen. As compared with control group, there was no significant difference in adverse events. Due to limited quantity and quality of the included studies, more high quality studies are needed to verify above mentioned conclusion.
引文
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19 王慧睿,郭淑利,李波,等.地西他滨联合CAG治疗老年急性髓系白血病的疗效观察.北方药学, 2017; 14(6):90-91.
20 闫雪华.地西他滨联合CAG方案治疗老年急性髓系白血病的疗效观察.中国现代药物应用, 2016; 10(9):111-112.
21 陈喜填,夏维林,林东,等.低剂量地西他滨序贯改良CAG方案对治疗骨髓增生异常综合征的临床疗效观察.吉林医学,2016; 37(5):1084-1086.
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25 宋扬,冷青,吴音,等.地西他滨联合CAG方案化疗治疗高危MDS的临床效果观察.中国冶金工业医学杂志, 2017; 34(1):123-124.
26 王萌,韩好好,郭荣,等.低剂量地西他滨序贯CAG方案治疗MDS-难治性贫血伴有原始细胞过多的临床疗效.中国实验血液学杂志, 2017; 25(5):1482-1486.
27 杨梨,罗红春,汪晶,等.地西他滨单药或联合半量CAG方案治疗骨髓增生异常综合征的临床研究.检验医学与临床,2016; 13(12):1601-1602.
28 杨晓哲.地西他滨联合小剂量化疗对MDS-RAEB患者疗效及生存期的改善作用.临床医学, 2016; 36(09):49-50.
29 于奇宁,常新东,刘先桃,等.地西他滨联合CAG方案治疗高危骨髓增生异常综合征疗效观察.疑难病杂志, 2013; 12(05):357-359.
30 张云平,吴文忠,崔国兴.地西他滨联合CAG方案与单纯CAG方案治疗中、高危骨髓增生异常综合征的疗效比较.中国实验血液学杂志, 2014; 22(05):1341-1344.
31 高志宏,赵爱红,陈方.减低剂量的地西他滨联合CAG方案治疗中高危骨髓增生异常综合征及难治性白血病的疗效分析.系统医学, 2017; 2(8):1-5.
32 范华,付榆,张宣,等.地西他滨联合半程和全程CAG方案治疗骨髓增生异常综合征和急性髓系白血病的效果比较.中国医药导报, 2016; 13(26):152-155.
33 高苏,仇惠英,金正明,等.地西他滨单药及联合半程和全程CAG方案治疗骨髓增生异常综合征和急性髓系白血病疗效观察.中华血液学杂志, 2014; 35(11):961-965.
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2 Juliusson G, Lazarevic V, H?rstedt AS, et al. Acute myeloid leukemia in the real world:why population-based registries are needed. Blood, 2012; 119(17):3890-3899.
3 Jianyong L, Yaoyu C, Yu Z, et al. Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in newly diagnosed elderly patients with acute myeloid leukemia.Oncotarget, 2015; 6(8):6448-58.
4 管俊,姜扬文,孙爱红,等.地西他滨联合半量预激方案对老年急性髓性白血病及高危骨髓增生异常综合征的影响.中华临床医师杂志(电子版), 2014; 8(21):3897-3900.
5 孟文俊,徐昕,戴秋新,等.地西他滨联合CAG方案治疗中高危骨髓增生异常综合征及老年急性髓系白血病15例报告.江苏大学学报(医学版), 2014; 24(6):535-537.
6 Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of the International Working Group(IWG)response criteria in myelodysplasia. Blood, 2006; 108(2):419-425.
7 Yan P, Frankhouser D, Murphy M, et al. Genome-wide methylation profiling in decitabine-treated patients with acute myeloid leukemia.Blood, 2012; 120(12):2466-2474.
8 Christman JK. 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation:mechanistic studies and their implications for cancer therapy. Oncogene, 2002; 21(35):5483-5495.
9 Oki Y, Aoki E, Issa JP. Decitabine-bedside to bench. Crit Rev Oncol Hematol, 2007; 61(2):140-152.
10 郝杰,王黎,王艳煜,等.地西他滨联合DAG方案等三种方案治疗复发、难治急性髓白血病疗效的比较分析.中华血液学杂志, 2014; 35(6):481-485.
11 杨华,朱海燕,姜孟孟,等.地西他滨治疗骨髓增生异常综合征和急性髓系白血病的临床观察.中国实验血液学杂志,2013; 21(1):121-125.
12 蔡成森,孙爱宁,仇惠英,等.地西他滨单药及联合AAG方案治疗初治急性髓系白血的临床观察.中华临床医师杂志(电子版), 2012; 6(19):6092-6094.
13 张娜,贾永前,青胜兰,等.地西他滨联合CAG方案对急性髓系白血病患者血IFN-γ,HBDH与LDH水平的影响.现代生物医学进展, 2017; 17(25):4963-4966.
14 蔡艳青.地西他滨联合CAG方案治疗老年急性髓系白血病临床疗效观察.山东医药, 2016; 56(5):90-91.
15 陈光,陆屹峰,朱玲玲,等.地西他滨联合CAG方案治疗老年急性髓系白血病临床疗效观察.中国医药科学, 2017; 7(11):62-64.
16 刘现民.地西他滨联合CAG方案治疗老年急性髓系白血病患者的效果与安全性分析.河南医学研究, 2015; 24(12):97-98.
17 陆小云,徐瑞琴.地西他滨联合CAG方案治疗老年急性髓系白血病的临床效果分析.临床血液学杂志, 2017; 30(5):697-700.
18 孙令凤,陈晓霞,王娟.地西他滨联合CAG方案治疗老年急性髓系白血病疗效观察.海南医学, 2017; 28(18):3037-3039.
19 王慧睿,郭淑利,李波,等.地西他滨联合CAG治疗老年急性髓系白血病的疗效观察.北方药学, 2017; 14(6):90-91.
20 闫雪华.地西他滨联合CAG方案治疗老年急性髓系白血病的疗效观察.中国现代药物应用, 2016; 10(9):111-112.
21 陈喜填,夏维林,林东,等.低剂量地西他滨序贯改良CAG方案对治疗骨髓增生异常综合征的临床疗效观察.吉林医学,2016; 37(5):1084-1086.
22 范振崴,张敏.地西他滨联合半量CAG方案与单纯CAG方案治疗老年人骨髓增生异常综合征的疗效比较.中国地方病防治杂志, 2017; 32(09):1014-1015.
23 关琦,于果,张海军.地西他滨联合CAG方案治疗骨髓增生异常综合征的疗效观察.检验医学与临床, 2015; 12(22):3339-3341.
24 卢远强,刘鹏,吴大海,等.地西他滨联合预激方案治疗骨髓增生异常综合征的临床研究.临床医学, 2017; 37(6):63-65.
25 宋扬,冷青,吴音,等.地西他滨联合CAG方案化疗治疗高危MDS的临床效果观察.中国冶金工业医学杂志, 2017; 34(1):123-124.
26 王萌,韩好好,郭荣,等.低剂量地西他滨序贯CAG方案治疗MDS-难治性贫血伴有原始细胞过多的临床疗效.中国实验血液学杂志, 2017; 25(5):1482-1486.
27 杨梨,罗红春,汪晶,等.地西他滨单药或联合半量CAG方案治疗骨髓增生异常综合征的临床研究.检验医学与临床,2016; 13(12):1601-1602.
28 杨晓哲.地西他滨联合小剂量化疗对MDS-RAEB患者疗效及生存期的改善作用.临床医学, 2016; 36(09):49-50.
29 于奇宁,常新东,刘先桃,等.地西他滨联合CAG方案治疗高危骨髓增生异常综合征疗效观察.疑难病杂志, 2013; 12(05):357-359.
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