摘要
目的:比较第二代酪氨酸激酶抑制剂(TKI)达沙替尼和尼洛替尼与第一代TKI伊马替尼对慢性髓系白血病(CML)患者的免疫调节作用。方法:对本中心使用达沙替尼(n=10)、尼洛替尼(n=26)或伊马替尼(n=44)治疗≥3个月的CML患者进行T细胞亚群等免疫指标的检测,并将上述指标与患者的临床疾病缓解状态及预后评估相关联分析。结果:达沙替尼、尼洛替尼和伊马替尼治疗的3组CML患者外周血Th1比例(Th1/CD4+T)高于正常值上限的例数分别为80.0%、16.6%和27.5%,其中达沙替尼组Th1比例值30.86%±9.75%显著高于尼罗替尼组17.37%±9.35%(P <0.001)和伊马替尼组20.79%±9.01%(P <0.001)。3组患者外周血CD8+T比例(CD8+T/Lymphocyte)各组无显著差异(P> 0.05), Th2比例(Th2/CD4+T)也无显著差异(P> 0.05)。Treg比例(Treg/CD4+T)达沙替尼组1.31%±0.10%显著低于尼洛替尼组2.65%±0.97%(P <0.001)和伊马替尼组2.99%±1.40%(P <0.001)。统计分析所有用药治疗后的患者:Th1比例高于正常上限25.8%的患者(n=28)中:84.62%为CCyR(完全细胞遗传学缓解),71.43%为MMR(主要分子生物学缓解),71.43%为MR4.5; Th1比例正常范围内11.8%-25.8%的患者(n=45)中:90.7%为CCyR,75.56%为MMR,75.56%为MR4.5;而Th1比例低于正常下限11.8%的患者(n=21)中:57.14%为CCyR,47.62%为MMR,47.62%为MR4.5。结果显示Th1升高组及正常组具有更高的缓解率及更深的缓解度。结论:本研究结果提示CML在TKI治疗中,Th1比例升高或正常提示更大的CCyR、MMR、MR4.5机率,而达沙替尼相比尼洛替尼及伊马替尼能显著提升患者Th1水平、降低Treg水平。
Objective: To compare the immunomodulatory effects of the 2nd generation of tyrosine kinase inhibitors(TKIs)-dasatinib and nilotinib as well as the 1st generation of TKI-imatinib on chronic myeloid leukemia(CML) patients. Method: To evaluate the T cell subtypes by flow cytometry on the CML patients of our center who received the treatment with dasatinib(n=10), nilotinib(n=26) or imatinib(n=44) for more than 3 months, and to analyze and correlate these data with the clinical remission situations and prognosis. Results: 80.0% of the patients in dasatinib group, 16.6% of the patients in nilotinib group and 27.5% of the patients in imatinib group respectively had a Th1 proportion in the peripheral blood(Th1/CD4+ T) above the upper limit of normal. More specifically, the Th1 proportion in dasatinib group(30.86%±9.75%) was significantly higher than that in nilotinib group(17.37%±9.35%)(P <0.001) and that in imatinib group(20.79%±9.01%)(P <0.001). Among the 3 groups, both the CD8+ T cell proportion(CD8+ T/Lymphocyte) and the Th2 proportion(Th2/CD4+ T) in the peripheral blood did not show a statistically significant difference. The Treg proportion(Treg/CD4+ T) in dasatinib group(1.31%±0.10%) was significantly lower than that in nilotinib group(2.65%±0.97%)(P <0.001) and that in imatinib group(2.99%±1.40%)(P <0.001).Among all the CML patients analyzed, for CML patients who had a Th1 proportion above the upper limit of normal(25.8%)(n=28), 84.62% of these patients obtained CCyR(complete cytogenetic response), 71.43% of these patients obtained MMR(major molecular response), 71.43% of these patients obtained MR4.5;for CML patients who had the Th1 proportion in the normal range(11.8%-25.8%)(n=45), 90.7% of these patients obtained CCyR, 75.56% of these patients obtained MMR, and 75.56% of these patients obtained MR4.5;for CML patients who had the Th1 proportion below the lower limit of normal(11.8%)(n=21), 57.14% of these patients obtained CCyR, 47.62% of these patients obtained MMR, and 47.62% of these patients obtained
作者
代景莹
杨曦
魏卿
李慧
黄晓兵
王晓冬
DAI Jing-Ying;YANG Xi;WEI Qing;LI Hui;HUANG Xiao-Bing;WANG Xiao-Dong(Department of Hematology,Sichuan Provincial People's Hospital,University of Electronic Science and Technology of China, Chengdu 611731,China;Department of Hematology,Sichuan Academy of Medical Sciences &Sichuan Provincial People's Hospital, Chengdu 610072,China;Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital,Chengdu 610072,China)
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2019年第1期25-32,共8页
Journal of Experimental Hematology
基金
四川省科技厅国际合作与交流项目(2018HH0114)
四川省医学科学院.四川省人民医院院青年人才基金(2017QN03)
电子科技大学中央高校基本科研业务费项目(2672018ZYGX2018J101)
