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


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).


CONCLUSIONS
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.
Claviez
Alexander
A
Department of Pediatrics, Germany Lymph Registry, University of Kiel, Schwanenweg 20, 24105 Kiel, Germany. a.claviez@pediatrics.uni-kiel.de
Tiemann
Markus
M
Lüders
Heike
H
Krams
Matthias
M
Parwaresch
Reza
R
Schellong
Günther
G
Dörffel
Wolfgang
W
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy / Q000532:radiotherapy / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D016539:Reed-Sternberg Cells / Q000821:virology; D016019:Survival Analysis; D014763:Viral Matrix Proteins / Q000032:analysis*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins