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Effect of EBV in Diffuse Large B-Cell Lymphoma

For Asian patients, overall survival and progression-free survival generally were shorter with EBV-positive DLBCL than with EBV-negative DLBCL.

The Epstein-Barr virus (EBV) has a pathogenic role in several lymphomas, including Burkitt lymphoma, extranodal NK–T-cell lymphoma nasal type, and Hodgkin lymphoma; however, the pathogenicity and prognostic role of EBV in diffuse large B-cell lymphoma (DLBCL) have not been established. In several case reports and small series, primarily from Asia, researchers have identified the presence of EBV in a subset of DLBCL patients. To further define the frequency and prognostic effect of EBV in DLBCL, investigators in Korea analyzed a retrospective cohort of 380 patients with de novo DLBCL who had pathologic specimens and clinical data available. DLBCL had been diagnosed in these patients from 1994 through 2005; 73% were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or rituximab-CHOP regimens. EBV positivity was determined by in situ hybridization for EBV RNA expression, and tissue samples were classified further into germinal center B-cell (GCB) or non-GCB by immunophenotypic analysis.

Thirty-four (9%) of the specimens were positive for EBV expression. Factors that were significantly associated with EBV positivity were older patient age, advanced-stage disease, higher International Prognostic Index score, presence of extranodal disease, and poor response to initial therapy. The proportion of GCB samples to non-GCB samples was similar in the EBV-positive and EBV-negative groups. After a median follow-up of 40.5 months, both progression-free survival and overall survival were shorter in the EBV-positive group than in the EBV-negative group (median, 13 vs. 36 months, P=0.018 for progression-free survival; 36 months vs. not yet reached, P=0.026 for overall survival). In a multivariate analysis, EBV-positivity was associated with significantly shorter overall survival in the non-GCB subgroup but not in the GCB subgroup.

Comment: These researchers confirm that EBV is expressed in DLBCL; the 9% rate here is similar to the 11.4% rate in an earlier Japanese report (Jpn J Cancer Res 2000; 91:1233). EBV positivity was associated with adverse outcomes, although whether this represents a direct role for EBV in either pathogenesis or therapeutic resistance is unclear. B-cell lymphomas represent a minority of non-Hodgkin lymphomas in Asia, unlike in Western countries where 85% to 90% of non-Hodgkin lymphomas are of B-cell origin, which suggests important etiologic differences. Whether these differences relate to genetic risk factors, coexisting infections such as hepatitis B or C, or other environmental exposures is uncertain. Defining frequency and risk for EBV in other populations of DLBCL patients will be enlightening. We might need to assess the role of an antiviral therapy in conjunction with standard induction regimens for EBV-positive DLBCL patients.

— Michael E. Williams, MD

Published in Journal Watch Oncology and Hematology August 14, 2007

Citation(s):

Park S et al. The impact of Epstein-Barr virus status on clinical outcome in diffuse large B-cell lymphoma. Blood 2007 Aug 1; 110:972-8.

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