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.
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.E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Feb;27(1):25-32. doi: 10.7534/j.issn.1009-2137.2019.01.005.
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.
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.
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 MR4.5. The above-mentioned data shows that the patients in high Th1 group and the normal Th1 group obtained the higher remission rate as well as the deeper remission level.
This study shows that during the CML treatment with TKIs, the increased or normal Th1 proportion indicates a bigger chance for CCyR, MMR, and MR4.5. Dasatinib may significantly increase the level of Th1 while decrease the level of Treg in the patients, as compared with nilotinib and imatinib.
比较第二代酪氨酸激酶抑制剂（TKIs）——达沙替尼和尼洛替尼以及第一代TKI——伊马替尼对慢性髓性白血病（CML）患者的免疫调节作用。
对本中心接受达沙替尼（n = 10）、尼洛替尼（n = 26）或伊马替尼（n = 44）治疗3个月以上的CML患者，通过流式细胞术评估T细胞亚群，并将这些数据与临床缓解情况及预后进行分析和关联。
达沙替尼组80.0%的患者、尼洛替尼组16.6%的患者和伊马替尼组27.5%的患者外周血中Th1比例（Th1/CD4 T）分别高于正常上限。具体而言，达沙替尼组的Th1比例（30.86%±9.75%）显著高于尼洛替尼组（17.37%±9.35%）（P<0.001）和伊马替尼组（20.79%±9.01%）（P<0.001）。3组中，外周血CD8 T细胞比例（CD8 T/淋巴细胞）和Th2比例（Th2/CD4 T）均未显示出统计学显著差异。达沙替尼组的Treg比例（Treg/CD4 T）（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）。在所有分析的CML患者中，对于Th1比例高于正常上限（25.8%）（n = 28）的CML患者，84.62%的患者获得完全细胞遗传学缓解（CCyR），71.43%的患者获得主要分子学缓解（MMR），71.43%的患者获得MR4.5；对于Th1比例在正常范围（11.8% - 25.8%）（n = 45）的CML患者，90.7%的患者获得CCyR，75.56%的患者获得MMR，75.56%的患者获得MR4.5；对于Th1比例低于正常下限（11.8%）（n = 21）的CML患者，57.14%的患者获得CCyR，47.62%的患者获得MMR，47.62%的患者获得MR4.5。上述数据表明，高Th1组和正常Th1组患者获得的缓解率更高，缓解程度更深。
本研究表明，在TKIs治疗CML期间，Th1比例升高或正常表明获得CCyR、MMR和MR4.5的机会更大。与尼洛替尼和伊马替尼相比，达沙替尼可能显著提高患者的Th1水平，同时降低Treg水平。
