伊马替尼联合化疗治疗Ph染色体阳性急性淋巴细胞白血病的分子学疗效与预后因素分析  

Molecular response and prognostic factors of patients with Philadelphia chromosome/BCR-ABL-positive acute lymphoblastic leukemia treated by imatinib with chemotherapy

作　　者：王婧[1] 黄晓军[1] 江滨[1] 秦亚溱[1] 鲍立[1] 江浩[1] 陈欢[1] 贾晋松[1] 杨申淼[1] 江倩[1] 

机构地区：[1]北京大学人民医院、北京大学血液病研究所,100044

出　　处：《中华血液学杂志》2014年第2期120-125,共6页Chinese Journal of Hematology

基　　金：北京市科学技术委员会基金（Z131100004013026）;北京市科技计划项目（Z111107067311070）

摘　　要：目的评估伊马替尼联合化疗治疗Ph染色体阳性急性淋巴细胞白血病（Ph＋ALL）的分子生物学疗效，并对预后因素进行分析。方法2006年5月至2012年7月连续收治的Ph＋ALL患者82例，在化疗的第1个疗程期加入伊马替尼治疗者48例；第2个疗程或之后加入伊马替尼治疗者34例。49例患者在巩固3～5个疗程后行异基因造血干细胞移植（allo．HSCT）。在每个疗程结束后用实时定量PCR法检测BCR．ABLmRNA表达水平用以评估分子生物学疗效。结果82例PhALL患者总完全缓解（cR）率为92．7％（82例中76例），其中第1疗程化疗CR率为76．8％（82例中63例）。第1疗程化疗时联合伊马替尼治疗者与未加伊马替尼者相比，CR率显著提高（93．8％对52．9％，P〈0．001）。在第1疗程诱导化疗后BCR．ABLmRNA下降91个对数级的患者占55．3％。在获得CR的患者中，累计复发率为27．6％；3年无疾病复发生存（DFS）率及3年总生存（Os）率分别为60．5％及70．2％。allo．HSCT是降低复发的独立预后因素（P〈0．001）。allo-HSCT、第1疗程诱导化疗时联合伊马替尼及女性是改善DFS的独立预后因素（P值分别〈0．01、0．05和0．01）。第1疗程诱导化疗后BCR-ABLmRNA下降≥1个对数级及allo-HSCT是改善OS的独立预后因素（P值分别为O．011和O．027）。结论第1疗程诱导化疗时联合伊马替尼、第1疗程诱导化疗后BCR-ABLmRNA下降91个对数级、接受allo-HSCT可以改善PhALL患者预后。Objective To evaluate the molecular response and prognostic factors of patients with Philadelphia chromosome/BCR-ABL-positive acute lymphoblastic leukaemia （Ph ~ ALL） treated by imatinib with chemotherapy. Methods From May 2006 to July 2012, 82 adult Ph＋ALL patients were enrolled in the study. Forty-eight patients combined imatinib in, and 34 patients after induction therapy. Forty-nine patients underwent allogeneic hematopoietic stem cell transplant （allo-HSCT） after 3 to 5 cycles of consolidation therapy. The molecular response of BCR-ABL mRNA was evaluated by real-time quantitative PCR in every chemotherapy course ending. Results The complete remission （CR） rate after the first cycle of induction chemotherapy was 76.8% （63/82）, with overall CR rate of 92.7% （76/82）. The CR rate in the patients combined imatinib in was higher than of those combined imatinib after the first cycle of induction chemotherapy （93.8% vs 52.9%, P〈0.001 ）. 55.3% patients BCR-ABL decreased 〉1 log after induction therapy. Among 76 CR patients, cumulative incidence of relapse was 27.6%, the probabilities of disease-free survival （DFS） and overall survival （OS） at 3 years were 60.5% and 70.2%, respectively, allo-HSCT was an independent favorable factor for decrease of leukemia relapse （P〈0.001）. allo- HSCT, imatinib combined in the first cycle of induction therapy and female were independentfavorable factors for DFS （P〈 0.01, 0.05 and 0.01, respectively）, BCR-ABL mRNA reduction at least 1 log from baseline after the first induction therapy and allo-HSCT were independent favorable factors for OS （P=0.011 and 0.027, respectively）. Conclusion Imatinib combined in the first cycle of induction therapy, BCR-ABL mRNA reduction at least 1 log from baseline after the first induction therapy and allo-HSCT imoroved outcomes of Ph＋ ALL oatients.

关 键 词：白血病 淋巴样 伊马替尼 融合蛋白类 BCR-ABL 造血干细胞移植 

分 类 号：R733.71[医药卫生—肿瘤]