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Up to 10 % of chronic lymphocytic leukemia (CLL) patients present with aggressive secondary B-cell lymphoma (most frequently diffuse large B-cell lymphoma, DLBCL) which may be clonally related to the CLL (i.e., Richter transformation, RT, 80 % of the cases) or de novo (20 % of the cases). Several genetic lesions associated with RT have already been identified, but the potential role of the Epstein-Barr virus (EBV) has been largely overlooked. In this study, we describe six CLL patients who developed a secondary EBV-positive (EBV + ) B-cell lymphoma (five DLBCL, one Hodgkin lymphoma) and compare their clinicopathological characteristics to ten CLL patients with EBV-negative (EBV - ) secondary B-cell lymphomas (all DLBCL). All 16 patients had a history of iatrogenic immunosuppression or chemotherapy. Eighty percent had received fludarabine as part of the CLL treatment. Most secondary lymphomas were clonally related to the previous CLL (3/4 EBV + , 7/7 EBV - cases tested). Notably EBV + RT was associated with a trend for older age at onset (median 72 vs. 63 years, p value &gt;0.05), longer interval between CLL and RT diagnosis (median 4.2 vs. 2.9 years, p value &gt;0.05), and shorter overall survival (median 4 vs. 10 months, p value &gt;0.05). These differences were not significant, probably due to small sample size. Immunohistochemical profiling suggested more frequent overexpression of TP53 and MYC in EBV - compared to EBV + secondary lymphoma. Based on this small retrospective single center series, we hypothesize that EBV + RT may constitute a separate subgroup of RT. Larger series are required to validate this suggestion.

Secondary B-cell lymphoma associated with the Epstein-Barr virus in chronic lymphocytic leukemia patients