Clinical Outcome and Survival of EBV-Positive Diffuse Large B-Cell Lymphoma.

EBV-positive diffuse large B-cell lymphoma (DLBCL) is a new entity included provisionally in the most recent WHO Classification of lymphoid neoplasms. It usually affects elderly patients and has a poor survival. The goal of this study was to evaluate clinical characteristics and survival of EBV-positive DLBCL.

Between January 2002 and June 2008, twenty patients with EBV-positive DLBCL were deemed eligible for the study. Of those, eighteen cases were evaluable. All cases were positive for the presence of EBV-encoded RNA (EBER) by in situ hybridization, and CD20 and/or Pax-5 expression by immunohistochemistry (IHC). Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the expression of bcl-6, CD10, CD30 and MUM-1 by IHC. The survival estimates were calculated using the Kaplan-Meier method and the log-rank test was used to compare the survival curves.

The mean age was 72.7 years (range 34-95 years). B symptoms occurred in 6 patients (33%). Four patients (22%) presented with stage I, 4 (22%) with stage II, 5 (28%) with stage III and five (28%) with stage IV. The IPI risk score was low in 6 patients (33%), low intermediate in 2 (11%), high intermediate in 6 (33%) and high in 4 (22%). Extranodal disease occurred in 10 patients (55%); the most common extranodal sites were gastrointestinal tract (n=5), lung (n=3), suprarenal gland (n=1), bone (n=1), skin (n=1), tonsils (n=1) and bone marrow (n=1). Of 13 evaluated cases, eleven cases (83%) were of non-germinal center and 2 cases (17%) were of germinal center subtype. According to the Oyama score, 3 cases (17%) had 0 risk factors, 11 patients (61%) had 1 risk factor and 4 (22%) had 2 risk factors with median survival of 41, 11 and 1.5 months, respectively. Eight patients (44%) did not receive chemotherapy because they had a poor performance status. Ten patients (56%) received chemotherapy, eight received CHOP and two received R-CHOP. Overall response was 70% with a complete response in 7 cases and progressive disease in 3. No patients exhibited a partial response. Median survival for the entire group was 10 months; the median survival for the treated group was 17 months while for the untreated group was 2.5 months. The 2 patients treated with R-CHOP obtained a complete response.

EBV-positive DLBCL is an aggressive entity with frequent extranodal disease and a poor prognosis. The latter appears to be due to high IPI scores, non-germinal center immunophenotype and/or the presence of EBV. Although, EBV-positive DLBCL seems to respond well to R-CHOP, the survival remains dismal. Prospective studies are needed to validate EBV's prognostic, predictive and therapeutic value in DLBCL in the post-rituximab era.

No relevant conflicts of interest to declare.