Impact of latent Epstein-Barr virus infection on outcome in children and adolescents with Hodgkin's lymphoma

Purpose The prognostic significance of latent Epstein-Barr virus (EBV) infection in Hodgkin's lymphoma (HL) is debated controversially. Especially in the pediatric age group, no conclusive data are available. Patients and Methods Eight hundred forty-two children and adolescents (median age, 13.7 years) from pediatric multicenter treatment studies HD-90 and HD-95 were studied for latent EBV infection in Hodgkin's and Beed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Results were compared with established risk factors. Results Two hundred sixty-three patients (31 %) were LMP positive. EBV infection correlated with sex (39 % male v 23 % female; P < .001), histologic subtype (69 % mixed cellularity v 22 % nodular sclerosis v6 % lymphocyte predominance; P < .001) and young age. With a median follow-up of 4.9 years, 820 patients (97 %) are alive. Probability of overall survival at 10 years (+/- standard deviation) for EBV-negative and -positive patients was 98.1 % +/- 0.6 % and 95.1 % +/- 1.4 %, respectively (P = .017 by log-rank test). A negative effect of EBV infection became evident for patients with nodular sclerosis subtype Bennett II (P = .02), and those treated for advanced stages (P = .003). In multivariate analysis, LMP positivity was an independent factor for adverse outcome (RR = 3.08). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89.1 % +/- 2.3 % and 84.1 % +/- 3.9 %, respectively (P = .86). Conclusion With effective combined treatment modalities in pediatric HL, latent EBV infection has no influence on FFS but is associated with an inferior overall survival in crucial subgroups.