The effect of T-lymphocyte sub-groups on prognosis during diagnosis of chronic lymphocyte leukemia

Purpose: The aim of this study was to examine the prognostic significance and effects on survival of T-lymphocyte subgroups in flow cytometry at diagnosis of Chronic Lymphocytic Leukemia patients. Method: 83 previously untreated CLL patients that were followed between September 1998 and September 2019 at Istanbul University Department of Hematology were enrolled retrospectively into the study. T-Lymphocyte subgroups in flow cytometry during diagnosis were examined; percentages, absolute values and ratios with malignant B-cells (MBC) were calculated. The patients' clinical and laboratory findings, stages, prognostic markers, progression and treatment status, progression free survival and overall survival times were analyzed. Continuous parameters were analyzed with Kruskal-Wallis and Mann-Whitney U tests. Categorical parameters were analyzed using Chi-squared test. Spearman analysis was used for correlation; Cox regression models and Kaplan-Meier tests were used for estimation of survival times. p-value < 0.05 was considered statistically significant. Results: There was no difference in T-lymphocyte parameters according to age, gender, modified Rai and Binet stage. CD3 percentage (p: 0.046) and CD4 percentage (p: 0.022) were lower in patients with beta-2 microglobulin > 3.5 mg/L. The CD7 percentage (p: 0.026), CD4/MBC (p: 0.033), CD8/MBC (p: 0.027) and CD7/MBC (p: 0.036) were lower in the multiple treatment group compared to the untreated group. No correlation was found between T-lymphocyte subgroups and time to first treatment (TTFT). CD4 percentage (p: 0.048), CD7 percentage (p: 0.020), CD4/MBC (p: 0.021), CD8/MBC (p: 0.035) and CD7/MBC (p: 0.012) were lower in patients with disease progression. The univariate regression model revealed T-lymphocyte percentages and ratios with MBC, HLA-DR percentage, stage, Beta-2 microglobulin, gamma globulin and treatment status as independent predictors of progression-free survival (PFS)(p < 0.05). CD3 percentage (p: 0.000), CD4 percentage (p: 0.001), CD8 percentage (p: 0.002) and CD7 percentage (p: 0.004) were lower in deceased patients. The univariate regression model revealed T-lymphocyte percentages and ratios with MBC, HLA-DR percentage, age, stage and Beta-2 microglobulin as independent predictors of overall survival (OS)(p < 0.05). Patients with CD3 percentage ≤ 10, CD4 percentage ≤ 7.5, CD8 percentage ≤ 6, CD7 percentage ≤ 18, CD4/MBC ≤ 0.1, CD8/MBC ≤ 0.2, and CD7/MBC ≤ 0.15 had shorter PFS (p < 0.05) and shorter OS (p < 0.05) than patients with values above these cut-off points. No significant difference was found between patients with and without CD4/CD8 inversion in terms of gamma globulin level, Beta-2 microglobulin level, CD38 percentage, TTFT, PFS and OS. Conclusion: Our study has shown that low T-lymphocyte percentages and low T-lymphocyte/MBC ratios at diagnosis are associated with poor prognosis, progressive disease and decreased survival. However, no association was found between CD4/CD8 inversion and progression, treatment time, and survival. Low T-lymphocyte/malignant B-cell ratios at diagnosis may be related with rapid CLL progression. Studies evaluating naive T-lymphocyte and differentiated T-lymphocyte subgroups, together with T-lymphocyte activation-inhibition markers would show the role of T-lymphocytes on CLL prognosis more clearly.