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Impact of Latent Epstein-Barr Virus Infection on Outcome in Children and Adolescents With Hodgkin's Lymphoma

From the Departments of Pediatrics and Hematopathology, German Lymph Node Registry, University of Kiel, Kiel; Second Department of Pediatrics, Helios Klinikum Berlin, Berlin; and Department of Pediatrics, University of Münster, Münster, Germany

Address reprint requests to: Alexander Claviez, MD, Department of Pediatrics, University of Kiel, Schwanenweg 20, 24105 Kiel, Germany; e-mail: a.claviez{at}pediatrics.uni-kiel.de

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 Reed-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 v 6% 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.

Supported by the Schleswig-Holstein Cancer Society, Kiel, Germany.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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