环磷酰胺和氟达拉滨联合利妥昔单抗治疗慢性淋巴细胞白血病疗效与安全性的Meta分析

Effectiveness and Safety of Fludarabine,Hosphamide,and Rituximab for Chronic Lymphocytic Leukemia:A Systematic Review and Meta-Analysis

[目的]系统评价环磷酰胺和氟达拉滨联合利妥昔单抗治疗慢性淋巴细胞白血病（CLL）疗效与安全性。[方法]计算机检索Pub Med、EMbase、The Cochrane Library、CBM、CNKI、VIP和Wan Fang Data,并手工检索相关期刊,全面收集环磷酰胺和氟达拉滨联合利妥昔单抗治疗慢性淋巴细胞白血病的相关的临床研究,检索时限均为建库至2016年12月。由2位评价员按照纳入与排除标准独立筛选文献、提取资料和评价纳入研究的偏倚风险后,采用Stata 13.0软件进行Meta分析。[结果]共纳入7篇文献,共1987例患者。Meta分析结果显示：FCR方案与FC方案相比,两者无进展生存期（HR=0.65,95%CI：0.56~0.74,P〈0.001）、总体生存率（HR=0.68,95%CI：0.52~0.85,P〈0.001）、完全缓解率（RR=1.882,95%CI：1.631~2.171,P〈0.001）、总反应率（RR=1.141,95%CI：1.085~1.200,P〈0.05）、Ⅲ/Ⅳ级中性粒细胞减少症发生率（RR=1.250,95%CI：1.005~1.555,P〈0.05）差异均有统计学意义;两者Ⅲ/Ⅳ级血小板减少症（RR=0.979,95%CI：0.554~1.731,P=0.94]、自身免疫性溶血性贫血（RR=0.60,95%CI：0.23~1.55,P=0.29）、恶心（RR=0.937,95%CI：0.566~1.552,P=0.80）、肺炎（RR=0.567,95%CI：0.256,1.262,P=0.16）发生率差异均无统计学意义。[结论]利妥昔单抗联合氟达拉滨和环磷酰胺组成的FCR方案可明显提高CLL患者的疗效,但需要注意不良反应的发生。

[Objective] To perform a systematic review with meta-analysis of clinical trials comparing FC and FCR in patients with CLL. [Methods] The databases such as Pub Med,EMbase,The Cochrane Library,CBM,CNKI,VIP and Wan Fang Data were searched from inception to December 2016. Two reviewers screened literature according to the inclusion and exclusion criteria,extracted data,and assessed the quality of included studies. Meta-analyses were performed using Stata 13.0 software. [Results] Seven RCTs involving 1987 patients with CLL were included. The results of meta-analyses showed that significant differences were found in the progression-free survival（PFS）（HR=0.65,95%CI：0.56~0.74,P〈0.001）,overall response（HR=0.68,95%CI：0.52~0.85,P〈0.001）,complete remission（RR=1.88,95%CI：1.63~2.17,P〈0.001）,and grade Ⅲ or Ⅳ neutropenia（RR=1.250,95%CI：1.005~1.555,P〈0.05）;but no significant differences were found in grade Ⅲ or Ⅳ thrombocytopenia（OR=0.979,95%CI：0.554 ~1.731,P =0.94）,autoimmune hemolytic anemia（RR =0.60,95% CI：0.23 ~1.55,P =0.29）,nausea（RR =0.937,95% CI：0.566 ~1.552,P =0.80） and Pneumonia（RR =0.567,95% CI：0.256 ~1.262,P =0.16）between FCR and FC regimen. [Conclusion] The FCR regimen can improve the progression-free survival,overall response and complete remission,it need take care about adverse reactions.