Plasma Epstein-Barr Virus (EBV) DNA as a Biomarker for EBV-associated Hodgkin lymphoma.

Objective: To assess plasma Epstein-Barr virus (EBV) DNA as a biomarker of tumour burden at diagnosis and during therapy in children with Hodgkin lymphoma. Design: Case-control study, with prospective follow-up of the Hodgkin lymphoma cohort (2007-2012). Setting: Pediatric Hematology Oncology unit of a tertiary care hospital in Delhi. Patients: Thirty children with Hodgkin lymphoma and 70 sex and age-matched controls (benign lymphadenopathy 19, non-lymphoid malignancy 29, Burkitt lymphoma 5, healthy children 17). Intervention: Positive EBV-staining on immunohistochemistry was defined as EBV-associated Hodgkin lymphoma. Plasma EBV real-time quantitative polymerase chain reaction (PCR) was tested at presentation, after first and last chemotherapy cycles, and on follow-up. Main outcome measures: Plasma EBV quantitative PCR was compared between cases and controls. Its kinetics was assessed during and after chemotherapy. Results: EBV quantitative PCR was positive in 19 (63%) Hodgkin lymphoma cases (range 500–430,000 copies/mL), with 87.5% accuracy (kappa=0.69) as compared with EBVimmunohistochemistry. Sensitivity and specificity of the quantitative PCR were 87.5% and 81.8%, respectively. Only boys showed positive EBV immunohistochemistry and/or quantitative- PCR positivity. All controls were quantitative-PCR negative. All quantitative-PCR positive cases with follow-up blood sample showed EBV clearance after the first cycle. A quantitative-PCR negative case in long-term remission became positive at relapse. EBV status did not influence survival. Conclusion: Plasma EBV-DNA, detectable in EBV-associated Hodgkin lymphoma, becomes undetectable early after initiating therapy. It can be used as a biomarker of treatment response in EBV-associated Hodgkin lymphoma.