Author:

Keywords:

Epstein-Barr virus, Chronic lymphocytic leukemia, Richter transformation, Immunosuppression-related lymphoproliferation, Immunomodulatory agent-related lymphoproliferation, Immunodeficiency-related lymphoma, Science & Technology, Life Sciences & Biomedicine, Hematology, Pathology, CENTRAL-NERVOUS-SYSTEM, RICHTER-SYNDROME, HODGKIN-LYMPHOMA, RHEUMATOID-ARTHRITIS, TRANSFORMATION, FLUDARABINE, RISK, METHOTREXATE, RECEPTOR, THERAPY, 3201 Cardiovascular medicine and haematology, 3202 Clinical sciences

Abstract:

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 >0.05), longer interval between CLL and RT diagnosis (median 4.2 vs. 2.9 years, p value >0.05), and shorter overall survival (median 4 vs. 10 months, p value >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.