Originally published as JCO Early Release 10.1200/JCO.2008.20.5138 on May 26 2009

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Latent Epstein-Barr Virus Infection of Tumor Cells in Classical Hodgkin's Lymphoma Predicts Adverse Outcome in Older Adult Patients

From the Departments of Pathology and Medical Biology and Hematology, University Medical Center Groningen, University of Groningen; the Comprehensive Cancer Center North Netherlands, Groningen; and the Department of Public Health, Erasmus Medical Center, Rotterdam, the Netherlands.

Corresponding author: Arjan Diepstra, MD, PhD, Department of Pathology and Medical Biology, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, the Netherlands; e-mail: a.diepstra{at}path.umcg.nl.

Purpose In classical Hodgkin's lymphoma (cHL), the impact of tumor cell Epstein-Barr virus (EBV) status on clinical outcome is controversial.

Patients and Methods We assessed failure-free survival (FFS) and relative survival (RS) in 412 patients with cHL and age-defined subgroups in a population-based study in the northern Netherlands. Tumor cell EBV status was positive in 34%, and the median follow-up time was 7.1 years. Patients' median age at diagnosis was 35 years (range, 7 to 91 years), and 63% had Ann Arbor stage I or II, 24% had stage III, and 12% had stage IV disease.

Results EBV status influenced 5-year FFS and RS only in patients from the age group 50 to 74 years. Five-year FFS was 60% in patients with EBV-positive versus 85% in EBV-negative tumors (P = .01). Five-year RS was 69% in patients with EBV-positive versus 82% in EBV-negative tumors (P = .03). After adjusting for histology, HLA class II expression by tumor cells, stage, presence of extranodal localizations and treatment, and the effect of positive EBV tumor status remained significant in FFS multivariate analysis (hazard ratio, 3.11; 95% CI, 1.28 to 7.53; P = .01).

Conclusion This study indicates that treatment failure in older adult patients with cHL is associated with positive tumor cell EBV status.

Supported by Koningin Wilhelmina Fonds (KWF) Grant No. RUG 2000-2315 from the Dutch Cancer Society and Nederlandse organisatie voor Wetenschappelijk Onderzoek–Medische Wetenschappen (NWO-MW) Grant No. 920-03-136 from the Dutch Organization of Scientific Research.

Presented at the 7th International Symposium on Hodgkin's Lymphoma, November 3-7, 2007, Cologne, Germany.

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

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