Prognostic significance of circulating plasma Epstein-Barr virus DNA in monitoring aggressive non-Hodgkin's lymphoma

Epstein-Barr virus (EBV) DNA copynumber quantification for blood specimens by real-time polymerase chain reaction (RT-PCR) is often used as a tool of screening for EBV-associated diseases or assessing treatment response. But the clinical value of plasma EBV-DNA has been rarely evaluated in patients with non-Hodgkin lymphoma (NHL). One hundred and eighty-two patients with NHL were recruited. Plasma EBV-DNA positive (>= 1000 copies/ml) was detected in 45 patients (PTCL, n = 16; NK/T, n = 13; DLBCL, n = 9; ATCL, n = 3; ALCL, n = 2; ANKL, n = 2). In all cases, plasma EBV-DNA was detectable (10(3)-10(7) copies/ml) at diagnosis. Plasma EBV-DNA positive was more common in mature T/NK neoplasms (80%) and related to more advanced disease stage (P = 0.004), presence of B symptoms (P<0.001) and higher lactate dehydrogenase (LDH) level (P<0.001). Plasma EBV-DNA positive showed distinctly worse overall survival (OS) than other patients with NHL and diffuse large B cell lymphoma (DLBCL) (P<0.001, each). In addition, the EBV-DNA positive patients with mature T/NK neoplasms also demonstrated substantially poorer OS and PFS (P = 0.009 and P = 0.008, respectively) compared with EBV-DNA negative (<1000 copies/ml). Multivariate analysis involving EBV DNA parameters demonstrated that it was an independent poor prognostic factor for OS in patients with NHL. These findings indicated that plasma EBV DNA load may be a useful potential biomarker and prognostic indicator in NHL.