Prognostic significance of Epstein–Barr virus DNA detection in pretreatment serum in diffuse large B‐cell lymphoma

<jats:p>It is still a matter of debate whether detection of Epstein–Barr virus (<jats:styled-content style="fixed-case">EBV</jats:styled-content>) <jats:styled-content style="fixed-case">DNA</jats:styled-content> in pretreatment serum has clinical implications for diffuse large B‐cell lymphoma. For this study, we measured <jats:styled-content style="fixed-case">EBV DNA</jats:styled-content> load in pretreatment serum from 127 diffuse large B‐cell lymphoma patients without any underlying immunodeficiency to evaluate its effects on clinical manifestations and prognosis. Anthracycline‐based chemotherapy in combination with rituximab was given as initial therapy for 119 patients (94%). Epstein–Barr virus <jats:styled-content style="fixed-case">DNA</jats:styled-content> was detected in 15 patients (12%), who were older (<jats:italic>P</jats:italic> = 0.005) and tended to be at a more advanced disease stage (<jats:italic>P</jats:italic> = 0.053). They showed significantly worse progression‐free survival (<jats:styled-content style="fixed-case">PFS</jats:styled-content>) and overall survival (<jats:styled-content style="fixed-case">OS</jats:styled-content>) than other patients (<jats:italic>P</jats:italic> < 0.001 each). This effect remained significant (<jats:italic>P</jats:italic> = 0.004 and <jats:italic>P</jats:italic> = 0.027, respectively) after adjustment for age, lactate dehydrogenase, performance status, stage, and extranodal sites. The status of <jats:styled-content style="fixed-case">EBV</jats:styled-content>‐encoded small <jats:styled-content style="fixed-case">RNA </jats:styled-content><jats:italic>in situ</jats:italic> hybridization was known for 123 patients; 6 of 8 positive patients (75%) and 9 of 115 negative patients (8%) had detectable <jats:styled-content style="fixed-case">EBV DNA</jats:styled-content> in pretreatment serum. While patients positive for <jats:styled-content style="fixed-case">EBV</jats:styled-content>‐encoded small <jats:styled-content style="fixed-case">RNA</jats:styled-content> had significantly worse <jats:styled-content style="fixed-case">PFS</jats:styled-content> and <jats:styled-content style="fixed-case">OS</jats:styled-content> than negative patients (<jats:italic>P</jats:italic> = 0.001 and <jats:italic>P</jats:italic> = 0.029, respectively), <jats:styled-content style="fixed-case">EBV DNA</jats:styled-content> detection in pretreatment serum was associated with poorer <jats:styled-content style="fixed-case">PFS</jats:styled-content> and <jats:styled-content style="fixed-case">OS</jats:styled-content> even for the 115 patients negative for <jats:styled-content style="fixed-case">EBV</jats:styled-content>‐encoded small <jats:styled-content style="fixed-case">RNA</jats:styled-content> (<jats:italic>P</jats:italic> < 0.001 each). These findings suggest that <jats:styled-content style="fixed-case">EBV DNA</jats:styled-content> detection in pretreatment serum may have an adverse prognostic impact for patients with diffuse large B‐cell lymphoma.</jats:p>