氟达拉滨+环磷酰胺+利妥昔单抗治疗慢性淋巴细胞白血病的临床疗效5年随访观察  

Five year follow up study of fludarabine plus cyclophosphamide and rituximab in the treatment of chronic lymphocytic leukemia

作　　者：马忠正 张宁宁 康伟莉 张永晓[1] 常涛涛 王淑华[1] 殷站茹[1] MA Zhongzheng;ZHANG Ningning;KANG Weili;ZHANG Yongxiao;CHANG Taotao;WANG Shuhua;YIN Zhanru(Department of Pediatric,Hudson International Peace Hospital,Hengshui,Hebei 053000,China)

机构地区：[1]哈励逊国际和平医院儿科,河北衡水053000

出　　处：《安徽医药》2020年第5期993-998,共6页Anhui Medical and Pharmaceutical Journal

基　　金：衡水市科技计划自筹经费基金项目(20150440)。

摘　　要：目的比较氟达拉滨+环磷酰胺(FC)方案与氟达拉滨+环磷酰胺+利妥昔单抗(FC+R)方案治疗慢性淋巴细胞白血病(CLL)的临床疗效及安全性差异。方法回顾性收集2013年1月至2016年6月哈励逊国际和平医院收治的65例CLL病例资料,采用FC方案治疗34例(FC组),FC+R方案治疗31例(FC+R组),比较两组化疗期间药物毒性反应、并发症及化疗结束后临床疗效,对获得客观缓解病例(ORR)进行独立影响因素分析,比较ORR获得者及亚组肿瘤无进展生存时间(PFS)与总生存时间(OS)。结果两组均完成4~6周期诱导化疗,化疗周期构成差异无统计学意义(P>0.05)。化疗结束后,FC+R组ORR获得率(87.1%比58.8%)、微小病残留(MRD)阴性率(45.2%比20.6%)均显著高于FC组(均P<0.05)。logistic分析表明,化疗后MRD阳性(OR?=5.023,95%CI:1.767~8.278)、基因突变或缺失(OR?=3.743,95%CI:1.868~5.619)是未获得ORR的独立影响因素(均P<0.05),FC+R方案则是独立保护因素(OR?=0.354,95%CI:0.162~0.546)(P<0.05)。FC+R组中位PFS时间长于FC组(未达到比47个月,P>0.05),两组均未达到中位OS;ORR病人亚组分析,FC+R组高危遗传学病例及MRD阳性病例中位PFS均显著长于FC组(45月比36月;47月比39月)(均P<0.05),各遗传学亚组与MRD亚组中位OS均差异无统计学意义(均P>0.05)。FC+R组血小板减少发生率显著高于FC组(35.5%比17.6%)(P<0.05),Ⅲ+Ⅳ度白细胞减少(16.1%比8.8%)、消化道反应(19.6%比8.8%)及Ⅰ+Ⅱ度贫血(25.8%比14.7%)、药物热发生率(25.8%比14.7%)均高于FC组(均P>0.05);两组继发感染等并发症发生率差异无统计学意义(8.8%比19.4%)(P>0.05)。结论FC+R方案较FC方案ORR获得率更高,能显著延长ORR病人高危遗传亚组与MRD阳性亚组PFS,主要增加血液学毒性、Ⅲ+Ⅳ度消化道反应及Ⅰ+Ⅱ度药物热。Objective Retrospective analysis on clinical efficacy of Fludarabine+Cyclophosphamide and Rituximab(FC+R)for the treatment of chronic lymphocytic leukemia(CLL),and compare the efficacy and safety of FC scheme versus FC+R scheme.Methods Clinical documents of 65 patients with CLL in Hudson International Peace Hospital from January 2013 to June 2016 were retro spectively collected,of which 34 cases with FC scheme and 31 cases with RC+R scheme,drug toxicities&complications and clini cal efficacy were recorded during or after chemotherapy.Logistic regression was introduced to explore the independent factors influ encing objective remission cases(ORR),and tumor progression free survival(PFS)and overall survival(OS)of ORR patients and subgroups with genetic and minimal residual disease(MRD)characteristics were compared.Results The two groups complet ed 4 6 cycles of induction chemotherapy,the composition of chemotherapy cycle with no statistical significance(P>0.05).The ORR rate(87.1%vs.58.8%)and MRD negative rate(45.2%vs.20.6%)in FC+Rgroupafter chemotherapy were significantly high er than those in FC group(P<0.05).Logistic analysis showed that MRD positive after chemotherapy(OR?=5.023,95%CI:1.767 8.278),gene mutation or deletion(OR?=3.743,95%CI:1.868 5.619)were independent factors without ORR(P<0.05).FC+R was an independent protective factor(OR?=0.354,95%CI:0.162 0.546)(P<0.05).FC+R group with PFS time was longer than the group FC(not reached vs.47 months,P>0.05),the two groups did not reach the median OS.The analysis of ORR subgroup showed FC+R scheme could significantly prolong PFS compared with FC scheme for patients with characteristics of high risk ge netics and MRD positive results(45 months vs.36 months;47 months vs.39 months)(all P<0.05).The genetics and MRD sub group with median OS showed no significant differences(P>0.05).The incidence of thrombocytopenia in FC+R group was significantly higher than the FC group(35.5%vs.17.6%)(P<0.05).The incidence ofⅢ+Ⅳleucopenia(16.1%vs.8.8%),digestive tract reaction(19.

关 键 词：白血病 淋巴细胞 慢性 B细胞 氟达拉滨 环磷酰胺 利妥昔单抗 影响因素分析 无病生存 毒性反应 

分 类 号：R733.72[医药卫生—肿瘤]