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Blood, 1 July 2004, Vol. 104, No. 1, pp. 243-249.
Prepublished online as a Blood First Edition Paper on March 18, 2004; DOI 10.1182/blood-2003-12-4197.
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NEOPLASIA
Quantification of circulating Epstein-Barr virus (EBV) DNA in the diagnosis and monitoring of natural killer cell and EBV-positive lymphomas in immunocompetent patients
Wing-Yan Au,
Annie Pang,
Carolyn Choy,
Chor-Sang Chim, and
Yok-Lam Kwong
From the Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, and the Department of Pathology, Queen Mary Hospital, University of Hong Kong, Hong Kong.
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 x 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 x 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.
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