慢性淋巴细胞白血病治疗及影响因素分析

Analysis of the treatment and influencing factors of chronic lymphocytic leukemia

目的：分析慢性淋巴细胞白血病（ CLL ）患者的临床资料、治疗效果及预后影响因素。方法收集2000年1月至2013年12月首都医科大学附属北京友谊医院血液内科诊治的65例CLL患者临床资料。使用流式分析检测患者Zeta链相关蛋白-70（Zap70）表达，反转录-聚合酶链反应检测免疫球蛋白重链可变区基因（ IgHV）突变程度，荧光原位杂交技术（ FISH）检测细胞遗传学异常。按治疗方法分为含氟达拉滨组（32例）、利妥昔单抗联合含氟达拉滨组（20例）和其他治疗组（13例）。含氟达拉滨组患者主要采用FC或FCD方案，每28天为1个疗程，至少治疗4个疗程以上，F为氟达拉滨25 mg/（m^2· d），共3 d，C为环磷酰胺200 mg/（ m^2· d），共3 d，D为地塞米松9 mg/（ m^2· d），共5 d。利妥昔单抗联合含氟达拉滨组患者采用利妥昔单抗联合氟达拉滨为基础的化疗，其中利妥昔单抗375 mg/m^2，化疗前1 d使用，共1 d， FCD方案同上。其他治疗组患者口服苯丁酸氮芥6 mg/（ m^2· d），服用30 d，每周监测血常规以调整剂量。比较不同治疗方法的总有效率。结果①有52例患者行Zap70检测，结果显示阳性患者16例，阴性患者36例，阳性患者总有效率低于阴性患者，差异有统计学意义[43．8％（7/16）比86．1％（31/36），P＜0．05]；有34例患者检测IgHV基因突变程度，其中基因突变阳性患者21例，阴性患者13例，阳性患者总有效率高于阴性患者，差异有统计学意义[95．2％（20/21）比61．5％（8/13），P＜0．05]；有24例患者使用FISH技术检测染色体，其中正常核型7例（29．2％），其余17例（70．8％）患者至少有1种遗传学异常。②含氟达拉滨组患者治疗后总有效率为71．9％（23/32），利妥昔单抗联合含氟达拉滨组治疗后总有效率为95．0％（19/20），其他治疗组治疗后总有效率为30．8％（4/13）。前2组与其他治疗组比较，总有效率差异有统计学意义（ P＜0．01）。结论 CLL患者临床特征和细胞遗传学标记及Zap70和IgHV基因突变与预后有关。含氟达拉滨或利妥昔单抗联合含氟达拉滨治疗方案使CLL治疗效果明显改善。

Objective To analyze the effect of treatment ,therapy response and prognosis of patients with chronic lymphocytic leukemia （ CLL） .Methods The clinical and laboratorial data of 65 CLL patients were ana-lyzed retrospectively .Flow cytometry was applied to detect Zeta-chain associated protein kinase 70 kDa （ Zap70 ） expression , mutational status of the immunoglobulin heavy chain variable （IgHV） gene were detected by reverse transcription polymerase chain reaction;chromosomal changes were checked by Fluorescence in situ hybridization （ FISH） test.The patients were divided into 3 groups by different treatment strategies： fludarabine based chemo-therapy（32 patients）, rituximab and fludarabine combining treatment （20 patients） and other treatments group （13 patients）.Fludarabine based chemotherapy included FC and FCD regime ,1 cycle for 28 days, over 4 cycles. F was Fludarabin 25 mg/（m^2· d） for 3 days, C was cyclophosphamide 200 mg/（m^2· d） for 3 days, D was dex-amethasone 9 mg/（ m^2· d） for 5 days.Rituximab and fludarabine combining treatment included rituximab 375 mg/m^2 for 1 day before chemotherapy .Other treatments included chlorambucil 6 mg/（ m^2· d） for 30 days;dose was adjusted by complete blood count analysis .Effective rates were compared among different groups . Results ①Zap70 expression was checked in 52 patients and 16 were positive .The effective rate was higher in negative patients than that in positive patients [43.8%（7/16） vs 86.1%（31/36）,P〈0.05].The mutational status of IgHV genes was detected in 34 patients and 21 were positive .The effective rate was higher in positive pa-tients than that in negative patients [95.2%（20/21） vs 61.5%（8/13）,P〈0.05].Twenty four cases performed Fluorescence in situ hybridization （ FISH） chromosomal changes test which showed that 17 patients had at least 1 genetic abnormalities and 7 havd normal karyotype .②Of 32 patients, 23 patients （71.9%） receiving fludarabine based chemotherapy achieved an effective rate （ complete response ＋partial response ） .Rituximab and fludarabine treatment achieved an effective rate of 95.0%（19/20）.Of 13 patients who received other treatment , effective rate was 30.8%（4/13）.Compared with other treatment groups, there was a statistical significance （P 〈0.01）. Conclusions CLL is a clinical and molecular heterogenous disease .Its clinical characteristics , cytogenetic analy-ses and Zap70 and IgHV gene mutation are related to prognosis .Fludarabine based chemotherapy and rituximab combined with treatment can improve CLL treatment .