title: Quantification of circulating Epstein-Barr virus (EBV) DNA in the diagnosis and monitoring of natural killer cell and EBV-positive lymphomas in immunocompetent patients.
abstract: In Epstein-Barr-virus (EBV)-positive lymphomas in immunocompetent patients, release of EBV DNA from tumor cells into the plasma might be useful for disease monitoring and prognostication. To test this hypothesis, we quantified serially plasma EBV DNA by quantitative polymerase chain reaction in 39 cases of EBV-positive (natural killer [NK] cell, n = 23; T cell, n = 8; B cell, n = 4; Hodgkin, n = 4) lymphomas. As control, EBV DNA was undetectable in 34 cases of EBV-negative lymphomas at diagnosis and during chemotherapy. In all cases of EBV-positive lymphomas, EBV DNA was detectable (10(5)-10(10) copies/mL) at diagnosis. It paralleled the clinical course, with EBV DNA becoming undetectable at remission and remaining elevated in refractory disease. On multivariate analysis, high-presentation EBV DNA (> 7.3 x 10(7) copies/mL) was significantly associated with an inferior overall survival (OS). Subgroup analysis of NK cell lymphomas, the largest cohort in this study, showed that presentation EBV DNA was correlated with disease stage and lactate dehydrogenase. On multivariate analysis, high-presentation EBV DNA (> 6.1 x 10(7) copies/mL) was significantly associated with an inferior disease-free survival. During treatment, patients with EBV DNA that showed further increases or failed to become undetectable had significantly inferior OS. In EBV-positive lymphomas, plasma EBV DNA is valuable as a tumor biomarker and for prognostication.
authors.affiliation: Department of Medicine, Queen Mary Hospital, University of Hong Kong.
authors.forename: Wing-Yan
authors.initials: WY
authors.lastname: Au
authors.forename: Annie
authors.initials: A
authors.lastname: Pang
authors.forename: Carolyn
authors.initials: C
authors.lastname: Choy
authors.forename: Chor-Sang
authors.initials: CS
authors.lastname: Chim
authors.forename: Yok-Lam
authors.initials: YL
authors.lastname: Kwong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004279:DNA, Viral / Q000097:blood*; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007121:Immunocompetence; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology*; D016399:Lymphoma, T-Cell / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D033581:Stem Cell Transplantation; D015996:Survival Rate; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000276:immunology / Q000821:virology
chemical_list: D004279:DNA, Viral