The Impact of Latent Epstein-Barr Virus Infection on Outcome in Children and Adolescents with Hodgkin’s Lymphoma.

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 due to small series.

842 children and adolescents (55% male) with a median age of 13.7 years (range, 2–20) from consecutive pediatric DAL/GPOH multicenter treatment studies HD-90 and HD-95 were studied for the presence of latent EBV infection in Hodgkin and Reed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Histology subtypes were as follows: nodular sclerosis (NSHL) 549, mixed cellularity (MCHL) 190, lymphocyte predominance (NLPHL) 90, lymphocyte depletion (LDHL) 6, lymphocyte-rich classical HL (LRCHL) 5, not specified 2. 88 patients had stage I, 470 had stage II, 172 had stage III and 112 had stage IV. B symptoms were present in 274 patients (33%). LMP status was compared with clinical parameters and established risk factors.

A total of 263 patients (32%) were LMP positive. EBV infection correlated with gender (male 39% vs. female 23%; p<.001), histological subtype (MCHL 69% vs. NSHL 22% vs. NLPHL 6%; p<.001) and age (<10 years 67% vs ≥10 years 28%, p<.001. With a median follow-up of 4.9 years (0.3–12) 820 patients (97%) are alive. Probability of overall survival at 10 years (±SD) for EBV negative and positive patients was 98±1% and 95±1%, respectively (p=.017 by log-rank test). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89±2% and 84±4%, respectively (p=.86). With respect to LMP status, a negative effect of latent EBV infection on overall survival became evident only for patients treated for advanced stages (p=.003), those with nodular sclerosis subtype Bennett II (p=.02) and B symptoms (p=.05). In a multivariate regression analysis, allocation to treatment group (RR=3.7) and LMP positivity (RR=3.01) were independent factors for overall survival and presence of B symptoms (RR=2.4) for FFS.

Under current highly effective polychemotherapy with or without involved field radiotherapy in pediatric HL, latent EBV infection has no influence on FFS in univariate and multivariate analysis. LMP positivity, however, seems to be associated with an inferior overall survival in some subgroups.