Veronique Dinand1, Anupam Sachdeva, Sanghamitra Datta, Sunita Bhalla, Manas Kalra, Chand Wattal, Nita Radhakrishnan. 1. Pediatric Hematology Oncology and BMT Unit, Department of Pediatrics, Institute of Child Health; *Department of Clinical Microbiology and Immunology; and #Department of Pathology; Sir Ganga Ram Hospital, New Delhi, India. Correspondence to: Dr Anupam Sachdeva, Pediatric Hematology, Oncology and BMT Unit, Department of Pediatrics, Institute of Child Health, Sir Ganga Ram Hospital, Delhi 110 060, India. anupamace@yahoo.co.in.
Abstract
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-lym-phoid 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 to 430,000 copies/mL), with 87.5% accuracy (kappa=0.69) as compared with EBV immunohistochemistry. 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.
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-lym-phoid 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 to 430,000 copies/mL), with 87.5% accuracy (kappa=0.69) as compared with EBV immunohistochemistry. 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.