The Inverse Correlation of Regulatory T Cells and Time to Initial Treatment in Chronic Lymphocytic B-Cell Leukemia.

Abstract 1238

Poster Board I-260

Regulatory T cells (T_reg) are thought to be potent suppressors of anti-tumor immunity and increased T_reg frequencies are correlated with poor prognosis in patients suffering from various tumor types. In the current study we analysed T_reg (CD3⁺CD4⁺CD25⁺CD127⁻) in the peripheral blood of 101 previously untreated chronic lymphocytic B-cell leukemia (B-CLL) patients as well as 170 healthy volunteers using flow cytometry. Statistical analysis was used for correlation with clinical data. T_reg of B-CLL patients expressed high numbers of FOXP3 and efficiently suppressed T cell proliferation. No significant difference in relative T_reg numbers between B-CLL patients and healthy controls could be observed, but T_reg numbers showed a significant negative correlation with time to initial treatment. Defining a cut-off of 9.75%, patients with higher T_reg showed significantly shorter time to initial treatment (median 4.4 yr, 95% CI 2.2 – 6.6 yr) when compared to the lower T_reg group (median not reached at 4.25 yr) (logrank P=0.001). Further subdivision of patients into quartiles according to T_reg numbers showed a clear dose-dependency (logrank P=0.027). T_reg numbers had significant prognostic power for time to initial treatment in univariate (P=0.001) as well as multivariate (P=0.037) Cox-regression analysis including Rai stage, IgVH mutational status, chromosomal aberrations and CD38 expression. In conclusion, higher T_reg numbers are significantly and independently correlated with shorter time to initial treatment in B-CLL in a dose-dependent fashion and show significant prognostic power for time to initial treatment. These results provide evidence for the role of T_reg in the clinical course of B-CLL.