[Effects of Tyrosine Kinase Inhibitors on the Th1 and Treg Cells of CML Patients].

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.