博纳吐单抗治疗急性淋巴细胞白血病有效性和安全性的Meta分析
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篇名: 博纳吐单抗治疗急性淋巴细胞白血病有效性和安全性的Meta分析
TITLE: Meta-analysis of clinical efficacy and safety of blinatumomab for acute lymphoblastic leukemia
摘要: 目的 系统评价博纳吐单抗治疗急性淋巴细胞白血病(ALL)的有效性与安全性,为其临床应用提供循证参考。方法计算机检索PubMed、Embase、WebofScience、Cochrane图书馆、中国知网、万方数据和中国生物医学文献服务系统,收集博纳吐单抗(试验组)对比传统化疗方案(对照组)治疗ALL的随机对照试验(RCT)和队列研究,检索时限均为建库起至2022年2月3日。筛选文献、提取资料后,采用Cochrane系统评价员手册5.1.0推荐的偏倚风险评估工具评价RCT的质量,采用纽卡斯尔-渥太华量表(NOS)评价队列研究的质量,采用RevMan5.4软件进行Meta分析;采用证据推荐分级的评估、制订与评价(GRADE)系统对结局指标的证据质量进行评价;采用倒漏斗图进行发表偏倚分析。结果共纳入8项研究,其中3项RCT、5项队列研究,共计2841例患者。Meta分析结果显示,试验组患者随访1年以上的总生存率[RR=1.30,95%CI(1.14,1.48),P<0.0001]、无复发生存率[RR=1.78,95%CI(1.50,2.12),P<0.00001]、完全缓解率[RR=1.42,95%CI(1.11,1.82),P=0.006]、震颤发生率[RR=16.98,95%CI(2.17,133.12),P=0.007]、细胞因子释放综合征发生率[RR=14.11,95%CI(3.43,58.01),P=0.0002]均显著高于对照组,两组患者头痛发生率比较差异无统计学意义[RR=1.31,95%CI(0.66,2.59),P=0.44]。试验组患者≥3级不良事件、感染、口腔炎、血小板减少症、发热性嗜中性粒细胞减少症、厌食、便秘、腹泻、腹痛、低血钾的发生率均显著低于对照组(P<0.05),咳嗽、红疹、低丙球蛋白血症、发热的发生率均显著高于对照组(P<0.05);两组患者的总不良事件、脓毒血症、贫血、白细胞降低、嗜中性白细胞减少症、淋巴细胞减少、恶心、呕吐、高血糖、低血压、高血压、转氨酶升高、鼻衄的发生率比较差异均无统计学意义(P>0.05)。按研究类型不同进行亚组分析的结果显示,无论是RCT还是队列研究,试验组患者随访1年以上的总生存率、无复发生存率、完全缓解率(队列研究除外)均显著高于对照组(P<0.05)。GRADE评价结果显示,本研究纳入的指标证据总体质量为低级。发表偏倚分析结果显示,本研究存在发表偏倚的可能性较小。结论博纳吐单抗治疗ALL的疗效较好,感染和消化系统不良事件的发生率较低,但震颤、咳嗽、红疹、发热、低丙球蛋白血症和细胞因子释放综合征的发生率较高。本研究纳入的指标证据质量普遍偏低。
ABSTRACT: OBJECTIVE To systema tically evaluate the efficacy and safety of blinatumomab for acute lymphoblastic leukemia (ALL)in order to provide evidence-based reference for clinical use. METHODS Retrieved from PubMed ,Embase,Web of Science,the Cochrane Library ,CNKI,Wanfang database and CBM during the inception to February 3,2022,randomized controlled trials (RCTs)and cohort studies of blinatumomab (experimental group ) versus conventional chemotherapy (control group )in the treatment of ALL were collected. After literature screening and data extraction ,the quality of RCTs was evaluated by the risk bias evaluation tool recommended by Cochrane handbook 5.1.0,and the quality of cohort studies was evaluated by the Newcastle-Ottawa scale (NOS). Meta-analysis was performed by RevMan 5.4 software. GRADE grading system was used to evaluate the evidence quality of outcomes. The publication bias was analyzed by inverted funnel plot. RESULTS A total of 8 studies were included ,involving 3 RCTs and 5 cohort studies ,with a total of 2 841 patients. Results of Meta-analysis showed that the overall survival rate more than one year [RR =1.30,95%CI(1.14,1.48),P<0.000 1],relapse-free survival rate [RR =1.78,95%CI(1.50,2.12),P<0.000 01],complete remission rate [RR =1.42,95%CI(1.11,1.82),P=0.006],the incidence of tremor [RR =16.98,95%CI(2.17,133.12),P=0.007],and the incidence of cytokine release syndrome [RR =14.11, 95%CI(3.43,58.01),P=0.000 2] in trial group were all significantly higher than control group ,but there was no statistical significance in the incidence of headache between two groups [RR =1.31,95%CI(0.66,2.59),P=0.44]. The incidence of adverse events with grade more than or equal to 3,infection,stomatitis,thrombocytopenia,febrile neutropenia ,anorexia, constipation,diarrhea,abdominal pain ,hypokalemia in trial group were significantly lower than control group (P<0.05). The incidence of cough ,rash and hypogamma globulinemia and fever in the trial group were significantly higher than control group (P<0.05). There was no statistical significance in the total incidence of adverse events ,sepsis,anemia,leucopenia,neutropenia, lymphopenia,nausea,vomiting,hyperglycemia,hypotension,hypertension,elevated transaminase or epistaxis between two groups(P>0.05). Results of subgroup analysis by study type showed that the overall survival rate ,relapse-free survival rate and complete response rate (except for cohort studies )of patients in trial group were significantly higher than control group in both RCTs and cohort studies (P<0.05). The results of GRADE evaluation showed that the overall quality of index evidence included in this study was low. There was little possibility of publication bias in this study based on the publication bias analysis. CONCLUSIONS Blinatumomab is effective in the treatment of ALL ,with low incidence of infection and adverse events of digestive system ,but high incidence of tremor ,cough,rash,fever,hypoproglobulinemia and cytokine release syndrome. The evidence quality of the indicators included in this study is generally low .
期刊: 2022年第33卷第12期
作者: 杨勇杰,张绮雯,鲁憬莉,关克磊,刘克锋,杨楠,杜书章,康建,张晓坚
AUTHORS: YANG Yongjie,ZHANG Qiwen, LU Jingli,GUAN Kelei,LIU Kefeng,YANG Nan,DU Shuzhang,KANG Jian,ZHANG Xiaojian
关键字: 博纳吐单抗;急性淋巴细胞白血病;Meta分析;有效性;安全性
KEYWORDS: blinatumomab;acute lymphoblastic leukemia ;meta-analysis;efficacy;safety
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