Quantification of circulating Epstein-Barr virus (EBV) DNA in the diagnosis and monitoring of natural killer cell and EBV-positive lymphomas in immunocompetent patients

• Published in: Blood Vol. 104; no. 1; pp. 243 - 249
• Main Authors: Au, Wing-Yan, Pang, Annie, Choy, Carolyn, Chim, Chor-Sang, Kwong, Yok-Lam
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.07.2004; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Case-Control Studies; DNA, Viral - blood; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - virology; Female; Hematologic and hematopoietic diseases; Herpesvirus 4, Human - genetics; Humans; Immunocompetence; Immunosuppression - adverse effects; Immunosuppression - methods; Killer Cells, Natural - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, T-Cell - blood; Lymphoma, T-Cell - drug therapy; Lymphoma, T-Cell - genetics; Lymphoma, T-Cell - immunology; Lymphoma, T-Cell - virology; Male; Medical sciences; Middle Aged; Neoplastic Cells, Circulating - pathology; Prognosis; Prospective Studies; Stem Cell Transplantation; Survival Rate; Treatment Outcome; Tumor Virus Infections - immunology; Tumor Virus Infections - virology; Gammaherpesvirinae; Human; Prognosis; Herpesviridae; Biological marker; Malignant hemopathy; Epstein Barr virus; Lymphoma; Virus; Natural killer cell; Immunosuppression; Surveillance; Lymphoproliferative syndrome; DNA; Diagnosis; Quantitative analysis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-12-4197

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 (105-1010 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 × 107 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 × 107 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.