PS1191 PROGNOSTIC SIGNIFICANCE OF REGULATORY T CELLS (TREGS) IN CHRONIC MYELOID LEUKEMIA PATIENTS TREATED WITH GENERIC IMATINIB

Abstract

Background:It has been observed that the proportion of regulatory T cells (Tregs) is elevated in untreated Chronic Myeloid Leukemia (CML) patients that curtail tumor‐specific immune response. The degree of imatinib‐related Treg inhibition correlates with CML prognosis. There is limited information on the dynamics of Tregs in CML patients treated with generic imatinib. We studied Treg proportions in newly‐diagnosed CML patients (at baseline and 3 months of treatment with generic imatinib).Aims:To evaluate Tregs in periperal blood of newly diagnosed patients of CML‐Chronic phase and their association with disease progression.Methods:Newly‐diagnosed adult CML patients in chronic phase were prospectively studied from July 2017 to March 2018. At baseline, a peripheral blood sample for Treg analysis was collected from CML patients before starting imatinib and from healthy controls. At 3 months, in addition to quantitative RQPCR for BCR‐ABL, a repeat peripheral blood sample was collected for Treg analysis. Treg percentage in peripheral blood was assessed by flowcytometry (triple laser BD FACS Canto II flow cytometer). Following sample acquisition on flow cytometer, the data was analysed using BD FACSDIVA software (Becton Dickinson, USA). Tregs were calculated as percentage of CD4+ T lymphocytes.Results:Fifty‐seven newly‐diagnosed CML patients and 30 age‐ and sex‐matched healthy controls were prospectively enrolled. The median age of the CML patients was 39 years (range 16 – 64years); 47.3% were males. The BCR‐ABL (IS) % at 3months was <1%, 1–10% and >10% in 15 (26.3%), 26 (45.6%) and 16 (28.1%) patients, respectively. The mean baseline Treg% of CML patients (3.61 ± 0.32%) was significantly higher than the mean Treg % of controls (1.58 ± 0.21%) (p < 0.001). The mean Treg% at 3 months in CML patients (1.73 ± 0.35%) was significantly lower than baseline Treg% (3.61 ± 0.32%) (p < 0.001). Baseline Treg% in CML patients showed significant positive correlation with Sokal score (r = 0.29), Hasford score (r = 0.33) and EUTOS score (r = 0.28) (p < 0.05). The baseline Treg% correlated significantly with the BCR‐ABL% at 3months (p = 0.03).Summary/Conclusion:We found a significantly higher proportion of Tregs in CML patients in chronic phase vis‐a‐vis healthy controls which significantly decreased with generic imatinib treatment at 3 months. The study results add evidence to the hypothesis that imatinib‐related Treg suppression is another novel mechanism through which it targets CML. Our findings lend support to the fact that generic imatinib is reasonably efficacious in restoring immunological milieu in CML patients.