High proportion of anergic B cells in the bone marrow defined phenotypically by CD21(-/low)/CD38- expression predicts poor survival in diffuse large B cell lymphoma.

BACKGROUND Diffuse large B cell lymphoma (DLBCL) is the commonest lymphoma that is highly aggressive where one-third of the patients relapse despite effective treatment. Interaction between the lymphoma cells and the non-clonal immune cells within the bone marrow microenvironment is thought to play a critical role in the pathogenesis of DLBCL. METHODS We used flow cytometry to characterize the proportion of B cell subpopulations in the bone marrow (N = 47) and peripheral blood (N = 54) of 75 DLBCL patients at diagnosis and study their impact on survival. RESULTS Anergic B cells in the bone marrow (BM), characterized as having CD21(-/low)/CD38- expression, influenced survival with high numbers (defined as > 13.9%) being associated with significantly shorter overall survival (59.7 months vs 113.6 months, p = 0.0038). Interestingly, low numbers of anergic B cells in the BM (defined as ≤13.9%) was associated with germinal center B cell type of DLBCL (p = 0.0354) that is known to have superior rates of survival when compared to activated B cell type. Finally, Cox regression analysis in our cohort of patients established that the inferior prognosis of having high numbers of anergic B cells in the bone marrow was independent of the established Revised International Prognostic Index (R-IPI) score. CONCLUSIONS High proportion of anergic B cells in the BM characterized by CD21(-/low)/CD38- expression predicts poor survival outcomes in DLBCL.