Expression Levels of CD38 in Tumor Cells and T-Cells Are of Prognostic Value in B-CLL.

Abstract

Purpose: CD38 expression level of tumor cells was identified as predictor for progression, overall survival and response to therapy in B-chronic lymphocytic leukemia. Though CD38 is involved in effector functions of T-cells, the prognostic value of CD38 expression in these cells has not been addressed in B-CLL before.Patients and Methods: CD38 expression levels in B-CLL cells and T-cells from 170 patients were analyzed by flow cytometry and correlated with clinical and molecular risk parameters.Results: CD38 expression levels significantly differed not only in the neoplastic clone but also in T-cells from B-CLL patients with low vs advanced stage and stable vs progressive disease. Combined analysis of CD38 in T-cells and B-CLL cells identified 4 subgroups of patients with distinct clinical course. Multivariate analysis including clinical (Rai stage, anemia) and molecular risk parameters (Zap-70 expression levels, IgVH mutational status) identified CD38 expression levels in B-CLL (RR 6.9; 95% CI: 2.4 to 20.2; p=.0004) and T-cells (RR 2.4; 95% CI 1.2 to 4.8; p=.0106) as independent prognostic factors. Furthermore, CD38 expression in T-cells as a risk factor for increased peripheral tumor load and progressive disease was significantly associated with male gender.Conclusion: Combined analysis of CD38 in tumor cells and T-cells is superior in predicting outcome in B-CLL than either parameter alone. Our data on the prognostic value of CD38+ T-cells in B-CLL in general, and their identification as male risk factor in particular strongly encourage further studies on their role on survival and proliferation of B-CLL cells and the underlying mechanisms.