Relationship between Seroresponse to Epstein-Barr Virus and Survival in Patients with Lymphoid Malignancies.

Introduction: Epstein-Barr virus (EBV) infection is a common life event that has been consistently associated to several lymphoproliferative malignancies. It is unclear to what extent EBV can be associated to clinical presentation and outcome of lymphomas.

Objectives: To evaluate the association between the seroresponse to EBV with the clinical presentation and survival in the different lymphoid malignancies.

Methods: As part of the EPILYMPH_Spain case-control study, 414 newly diagnosed lymphoma cases and 488 controls, age and sex matched to the cases, were systematically recruited in a single center during 20 months (starting in 1998). From all subjects, a blood sample was drawn at diagnosis and EBV serostatus was evaluated through ELISA assays to measure IgG reactivity against immunodominant epitopes of EBNA1(BKRF1) and VCA-p18 (BFRF3). Further, immunoblot analysis was performed to evaluate distinct antibody patterns to EBNA1, VCA18, VCA-p40 (BdRF1) and Zebra (BZLF1). These patterns were classified into two groups: reactive (with wide responsiveness to the different EBV proteins) and non-reactive (with an IgG reactivity restricted to a limited number of EBV proteins). Statistical differences between each group were analyzed using Chi-square test for categorical data and T-Student test for continuous data. Survival analysis was performed by Kaplan-Meier techniques and compared with the log rang test. Values of p<0.05 were considered to be statistically significant. All data were adjusted for age and sex.

Results: Twenty-four percent (101/414) of the cases and 17% (86/488) of the controls had an EBV reactive response pattern (p= 0.012). Among cases, 29% females versus 20% of males presented an EBV reactive pattern (p= 0.031), with no differences regarding median age. When we agrupated the different lymphoid malignancies into the 3 most important entities, differences in the prevalence of EBV seropositivity were found: B-cell neoplasms (25%), Hodgkin lymphomas (12%) and T-cell neoplasms (34%), p=0.05. When analyzing the different WHO entities, in myeloma patients, EBV reactive pattern was found to be associated to an early stage disease (29% Stage 1 vs 5% Stage 2–3; p= 0.038) and a longer median survival (not reached vs 38 months; p= 0.02).

Conclusions: EBV seroprevalence is higher in lymphoma patients, with a slight predominance in females. EBV reactive pattern seems to be associated to early stage myeloma, which implicates a better survival.