对伊马替尼反应差的慢性髓系白血病患者换用第Ⅱ代酪氨酸激酶抑制剂的疗效观察  

Clinical Efficacy of Switching to 2nd Generation of Tyrosine Kinase Inhibitor on CML Patients at Poor Responses to Imatinib

作　　者：乔建辉[1] 张泽川[1] 姚波[1] 李冰霞[1] 郭梅[1] 孙琪云[1] 胡锴勋[1] 余长林[1] 董征[1] 艾辉胜[1] 

机构地区：[1]军事医学科学院附属医院血液科,北京100071

出　　处：《中国实验血液学杂志》2015年第1期65-69,共5页Journal of Experimental Hematology

基　　金：首都临床特色应用研究(Z121107001012082)

摘　　要：目的:探讨第一代酪氨酸激酶抑制剂(TKI)伊马替尼治疗初治慢性髓系白血病慢性期(CML-CP)患者疗效差(疗效欠佳、失败或不耐受)时换用第2代TKI的时机及疗效。方法:观察2009年2月至2012年2月间9例初治CM L-CP患者应用伊马替尼后(3例不耐受,6例治疗失败或欠佳)换用第Ⅱ代TKI治疗的效果及副作用。结果:3例不耐受患者换第2代TKI后均获得了满意的疗效,均在换用3个月达到完全细胞遗传学缓解(CCyR),分别在3至6个月达到主要分子生物学缓解(MMR),疗效均达到欧洲白血病网(ELN)指南的疗效满意标准,但有1例患者在用药3个月后出现胸水而暂时停药,仍持续缓解。6例疗效不理想患者中2例经伊马替尼治疗失败的患者换用第2代后仍疾病进展,其中1例有效但耐受性差,进展至加速期后进行了单倍体造血干细胞移植获治愈;1例治疗失败,发生急变,在化疗后因严重感染去世;另4例疗效欠佳患者均在换用第2代TKI后3-12个月内达到了MMR,疗效满意,已分别持续CMR 12-36月。结论:CML-CP患者在伊马替尼疗效不满意时应尽早换用第2代TKI治疗,而且越早越受益,有可能获得最佳疗效。Objective： This study was to investigate the timing and clinical efficacy of switching to the 2nd generation of tyrosine kinase inhibitor （TKI） for CML patients at poor response to imatinib （ dissatifed efficacy or intolerance）. Methods：The therapeatic efficacy and side reaction of switched 2nd TKI in patients with newly diagnsed CML-CP who poorly responded to imatinib were observed, anong them 3 cases were intolerant, 6 cases did not acquire satisfied efficacy. Results： After switching to 2nd generation TKI, 3 patients with intolerance achieved complete cytogenetic remission （CCyR） in 3 months, and major molecular remission （MMR） in 3 - 6 months. All of them achieved optimal efficacy according to European Leukemia Network （ELN）, but the pleural effusion appeared in 1 case after use of 2nd generation of TKI for 3 months, and the dadatinib was stoped temporally, and the curative efficacy still was maintained. Among 6 cases with poor efficacy by treatment with imatinib, 2 cases with BCR/ABL mutation progressed after switching 2nd generation of TKI, out of them 1 case with poor tolerance progeressed to the accelerated phase, but was cured by haploidentical allogeneic hematopoictic stem cell transplantation, 1 case progressed to blastic crisis and died of serious infection; the another 4 cases achieved MMR in 3 - 12 months after using 2nd generation of TKI, and maintained CMR for 12 -36 months. Conclusion：CML-CP patients without the optimal response to imatinib should be treated by switching to 2nd generation of TKI as soon as possible, and thereby patients may acquired satisfactory theralaentic efficacy.

关 键 词：慢性髓系白血病 酪氨酸激酶抑制剂 伊马替尼 

分 类 号：R733.72[医药卫生—肿瘤] R979.1[医药卫生—临床医学]