42例伊马替尼耐药慢性髓系白血病患者临床分析

摘要

目的:分析伊马替尼耐药的慢性髓系白血病(CML)患者中激酶突变的比例、相关因素及二代药物的有效性及安全性.方法:应用COX比例风险回归模型对影响激酶突变的各种因素进行单因素和多因素分析,并评估应用第二代酚氨酸激酶抑制剂(TKI)的有效性及安全性.结果:42例患者中19例共检测出13种突变22次,其中F359V 4次,E255K 3次,F359C、F317L、T315I、Y253H各2次,D256R、C250R、D276G、F486S、M244V、Y256H、G250E各1次,3例患者为混合突变.根据激酶突变结果选择患者敏感的酪氨酸激酶抑制剂,尼洛替尼不良反应以皮疹、液体潴留为主,而达沙替尼不良反应以眼睑水肿、胆红素升高为主.结论:白细胞计数、脾脏肿大程度、染色体核型、疾病分期、获得完全细胞遗传学缓解(CCyR)时间为激酶突变的相关因素,换用第二代TKI药物疗效明确,患者耐受性良好.%Objective:To analyze the kinase mutation ratio,related factors,effectiveness and safety of the second generation drugs for imatinib-resistant patients with chronic myeloid leukemia (CML).Methods:COX proportional hazard regression model was used for unvariate and multvariate analysis of various factors affecting the kinase mutation and for evaluating the effectiveness and safety of second generation tyrosine kinase inhibitor(TKI).Results:13 kinds of mutation were detected in 19 out of 42 cases for 22 times,including 4 times of F359V,3 times of E255K,2 time for F359C,F317L,T315I,Y253H,1 time for D256R,C250R,D276G,F486S,M244V,Y256H and G250E,3 cases with mixed mutations.The main adverse effects of patients receiving nilotinib were skin rash and fluid retention,while that for patients receiving dasatinib were eyelid edema and elevated bilirubin.Conclusion:The WBC count,spleen enlargement degree,chromosome karyotypes,disease staging,drug used before treatment and time of acheiving CCyR are the related factors of the kinase mutations,but the patients receiving the second generation TKI can survive well.