利妥昔单抗联合FC方案治疗慢性淋巴细胞白血病的疗效和安全性系统评价

Effectiveness and Safety of FCR Regimen for Chronic Lymphocytic Leukemia:A Systematic Review

目的系统评价利妥昔单抗与氟达拉滨和环磷酰胺(FC)组成的FCR方案对慢性淋巴细胞白血病(CLL)的治疗效果和安全性。方法计算机检索PubMed、Cochrane Library、SpringerLink、CNKI和CBM数据库2000～2011年期间发表的关于FCR方案和FC方案比较治疗CLL的随机对照试验(RCT)。由两位研究者独立进行文献筛选、资料提取和质量评价后,采用RevMan 5.0软件进行Meta分析。结果共纳入3个RCT,共1 623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(P<0.001)、总体生存率[OR=1.94,95%CI(1.49,2.53),P<0.000 01]、完全缓解率[OR=2.54,95%CI(2.00,3.22),P<0.000 01]、Ⅲ/Ⅳ级中性粒细胞减少症发生率[OR=1.60,95%CI(1.33,1.92),P<0.000 01]、总的Ⅲ/Ⅳ级不良反应发生率[OR=1.72,95%CI(1.35,2.20),P<0.000 1]差异均有统计学意义;而两者部分缓解率[OR=0.74,95%CI(0.35,1.55),P=0.43]、Ⅲ/Ⅳ级血小板减少症[OR=0.97,95%CI(0.74,1.27),P=0.83]、自身免疫性溶血性贫血[OR=0.86,95%CI(0.59,1.27),P=0.45]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方案可明显延长CLL的无进展生存期,提高总体生存率和完全缓解率。但部分患者也会出现Ⅲ/Ⅳ级中性粒细胞减少症、血小板减少症、自身免疫性溶血性贫血、恶心呕吐等不良反应。

Objective To assess the clinical effectiveness and safety of fludarabine and cyclophosphamide（FC） combined with rituximab chemotherapy regimen（FCR regimen） for patients with chronic lymphoblastic leukemia（CLL）.Methods The databases such as PubMed,The Cochrane Library,SpringerLink,CNKI,and CBM were searched from 2000 to 2011.The randomized controlled trials（RCTs） on FC regimen versus FCR regimen for CLL were retrieved.The methodological quality of the included studies was assessed according to the Cochrane Reviewer＇s Handbook,and meta-analyses were performed using RevMan 5.0 software.Results Three RCTs involving 1？623 patients with CLL were included.The results of meta-analyses showed that significant differences were found in the progression-free survival（PSF）（P〈0.001）,overall response（OR=1.94,95%CI 1.49 to 2.53,P〈0.000？01）,complete remission（OR=2.54,95%CI 2.00 to 3.22,P〈0.000？01）,and grade III or IV neutropenia（OR=1.60,95%CI 1.33 to 1.92,P〈0.000？01）;but no significant differences were found in the partial response（OR=0.74,95%CI 0.35 to 1.55,P=0.43）,grade III or IV thrombocytopenia（OR=0.97,95%CI 0.74 to 1.27,P=0.83） and autoimmune hemolytic anemia（OR=0.86,95%CI 0.59 to 1.27,P=0.45） between FCR and FC regimen.Conclusion The FCR regimen can improve the progression-free survival,overall response and complete remission.Meanwhile,it sometimes increases the incidence of Grade III or IV events,such as neutropenia,thrombocytopenia,autoimmune hemolytic anemia and nausea and vomiting.