慢性髓系白血病患者酪氨酸激酶抑制剂相关的肝脏不良反应  

Hepatic adverse events associated with tyrosine kinase inhibitors in patients with chronic myeloid leukemia

作　　者：窦雪琳 王莎莎 房继莲[2] 于露[1] 任欣[1] 黄晓军[1] 江倩[1] Dou Xuelin;Wang Shasha;Fang Jilian;Yu Lu;Ren Xin;Huang Xiaojun;Jiang Qian(Peking University People＇s Hospital,Peking University Institute of Hematology,Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation,Beijing 100044,China)

机构地区：[1]北京大学人民医院北京大学血液病研究所造血干细胞移植治疗血液病北京重点实验室,100044 [2]北京大学人民医院北京大学肝病研究所

出　　处：《中华内科杂志》2018年第9期649-655,共7页Chinese Journal of Internal Medicine

基　　金：国家自然科学基金（81770161）

摘　　要：目的 探索接受不同酪氨酸激酶抑制剂（TKI）治疗的慢性髓系白血病慢性期（CML-CP）患者肝脏不良反应的发生率及其影响因素.方法 回顾北京大学人民医院服用伊马替尼、达沙替尼或尼洛替尼的CML-CP患者的肝脏生化项目数据[包括丙氨酸转氨酶（ALT）、伴ALT升高的天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）和总胆红素（TBil）],分析患者服药6个月内肝脏生化项目异常的发生率和严重程度及其影响因素.结果 共收集436例患者,其中服用伊马替尼271例,达沙替尼58例,尼洛替尼107例.3组患者出现任意一项肝脏生化项目异常的比例分别为21.8％（59/271）、15.5％（9/58）和32.7％ （35/107）,多为常见不良反应事件评定标准（CTCAE）1、2级毒性,无重度肝损伤.多因素分析显示,服用尼洛替尼[OR=2.9（1.3～6.6）,P=0.012和OR=4.4（1.2～15.6）,P=0.023]和男性[OR=2.3（1.4～3.9）,P=0.002和OR=3.0（1.2～7.6）,P=0.018]与患者发生肝脏生化项目异常和发生中度肝脏生化项目异常均显著相关.结论 接受伊马替尼、达沙替尼或尼洛替尼治疗的CML-CP患者肝脏耐受性良好.服用尼洛替尼和男性患者与发生TKI相关的肝脏不良反应相关.Objective To explore the incidence and severity of hepatic adverse events （AEs） and identify factors associated with hepatic AEs in patients with chronic myeloid leukemia （CML） in chronic phase （CP） treated with tyrosine kinase inhibitors （TKIs）.Methods Liver biochemistry parameters [including ALT（alanine aminotransferase）,AST（aspartate aminotransferase）,ALP（alkaline phosphatase）,and TBil（total bilirubin）] during the first 6 months on imatinib （Gleevec（R））,dasatinib （Sprycel（R）） or nilotinib （Tasigna（R）） in CML-CP patients were collected and analyzed retrospectively.Results A total of 436 patients were enrolled in this study,including 271 with imatinib,58 with dasatinib,and 107 with nilotinib.The incidences of any abnormality of liver injury were 21.8%（59/271）,15.5%（9/58） and 32.7%（35/107） in the imatinib,dasatinib and nilotinib groups,respectively.Most of the hepatic AEs were CTCAE grade 1 or 2 and mild or moderate liver injury except 1.9% of TBil CTCAE grade 3 in the nilotinib group.Multivariate analyses showed nilotinib [OR=2.9（1.3-6.6）,P=0.012;OR=4.4（1.2-15.6）,P=0.023] and male gender [OR=2.3（1.4-3.9）,P=0.002;OR=3.0（1.2-7.6）,P=0.018] were significantly associated with moderate liver impairment.Conclusions TKIs including imatinib,dasatinib and nilotinib were well tolerated with mild to moderate hepatic AEs in CML-CP patients.Nilotinib and male sex were associated with occurrence of liver biochemistry abnormalities and moderate hepatic injury.

关 键 词：白血病 髓系 慢性 酪氨酸激酶抑制剂 肝脏不良反应 

分 类 号：R733.72[医药卫生—肿瘤]