摘要：
Objective To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph +ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared.Results Of 76 Ph+ ALL patients,first-generation TKI was administered in 57 cases,second-generation TKI in 19 cases,including 10 cases of nilotinib and 9 cases of dasatinib.There was no significant difference in age,WBC counts,additional chromosomal abnormalities,time form diagnosis to transplantation,transplantation type,conditioning regimen or TKI initiation time between the two groups.Complete remission (CR) rates at the fourth week of induction therapy in first-generation TKI group and second-generation TKI group was 93.0％ and 94.7％ (P=1.000),respectively.Major molecular response (MMR,BCR-ABL/ABL reduce 3 log) rates meanwhile were 46.0％ and 40.0％ (x2 =0.169,P =0.681).Relapse rates before transplantation were 14.0％ and 10.5％ (P =1.000).MMR rates before transplantation were 54.4％ and 68.2％ (x2 =1.152,P=0.283).The 2-year overall survival (OS) rates of first-generation and second-generation TKI group wcrc 62.0％ and 94.7％ (x2=5.765,P =0.016),2-year event-free survival (EFS) rates were 46.3％ and 84.2％ (x2 =5.644,P=0.018),respectively.Univariate analysis showed that second-generation TKI could improve OS (HR =0.126,95％CI 0.017-0.939,P =0.043).Multiple factors analysis showed that second-generation TKI (HR=0.267,95％ CI 0.081-0.873,P=0.029) and MMR before transplantation (HR =0.496,95％ CI 0.254-0.968,P =0.040) were good independent prognostic factors of EFS.Conclusions There was significant difference in the efficacy of second-generation TKI and first-generation TKI for Ph+ ALL patients treated by allo-HSCT.First-line administration of second-generation TKI showed better efficacy than that of first-generation TKI for Ph+ ALL patients.%目的 探讨一线应用一代与二代酪氨酸激酶抑制剂(TKI)联合化疗序贯allo-HSCT治疗Ph+急性淋巴细胞白血病的疗效差异.方法 回顾性分析2011年6月至2015年12月行allo-HSCT的76例Ph+ALL患者的临床特征及转归,比较一线应用一代TKI与二代TKI的疗效是否存在差异.结果 一线应用伊马替尼患者57例,为一代TKI组;应用二代TKI患者19例(尼洛替尼10例,达沙替尼9例),为二代TKI组.两组患者在年龄、初诊时WBC、染色体核型、诊断至移植时间、移植类型、预处理方案等差异均无统计学意义.一代和二代TKI组比较:诱导治疗4周完全缓解率分别为93.0％和94.7％(P=1.000),诱导治疗4周主要分子学反应(MMR,BCR-ABL拷贝数较基线下降3个对数级)率分别为46.0％和40.0％(x2=0.169,P=0.681),移植前复发率分别为14.0％和10.5％(P=1.000),移植前MMR率分别为54.4％和68.4％(x2=1.152,P=0.283),差异均无统计学意义.一代和二代TKI组2年总生存(OS)率分别为62.0％、94.7％,2年无事件生存(EFS)率分别为46.3％、84.2％,两组OS、EFS时间差异均有统计学意义(x2=5.765,P=0.016;x2=5.644,P=0.018).单因素分析显示二代TKI可改善OS(HR=0.126,95％ CI 0.017～ 0.939,P=0.043).多因素分析显示应用二代TKI(HR=0.267,95％ CI0.081～ 0.873,P=0.029)和移植前获得MMR(HR=0.496,95％CI 0.254～ 0.968,P=0.040)是EFS预后良好的独立影响因素.结论 本回顾性小系列研究结果提示,TKI联合化疗并序贯allo-HSCT治疗Ph+ALL患者时,一线应用二代TKI的长期疗效优于一代TKI.
