Frequency and clinical correlates of elevated plasma Epstein-Barr virus DNA at diagnosis in peripheral T-cell lymphomas

Abstract

Epstein-Barr virus (EBV)-encoded RNAs (EBER) in tumor tissue and cell-free plasma EBV-DNA (pEBVd) are detected in EBV-associated lymphomas. Studies have suggested that EBER+ peripheral T-cell lymphomas (PTCL) have worse prognosis but the role of EBV in these neoplasms remains unclear. pEBVd is quantitative and more easily amenable to standardization than EBER, but frequency of pEBVd detection, clinical impact and agreement with EBER status in PTCL are unknown. We retrospectively assessed frequency of detectable pre-treatment pEBVd, presence of EBER in tumor tissue, and outcomes in 61 of 135 EBV-assessable PTCL patients. Fifteen of 61 patients (24.5%, 95% CI: 14-37%) were pre-treatment pEBVd+, with no significant differences in baseline characteristics or treatment between pEBVd+ and pEBVd- patients. EBER-ISH was performed on 10 pEBVd+ and 35 pEBVd- tumors. All 10 pEBVd+ patients were EBER+, but 9 pEBVd- patients were also EBER+. With median follow up of 24 months (range 1-96), overall survival (OS) was shorter in pEBVd+ compared to pEBVd- patients (13 vs. 72 months; p = 0.04). In our retrospective study, pre-treatment pEBVd was elevated in 25% of PTCL patients, was highly specific for EBER+ tumors, and was associated with shorter survival. pEBVd should be further explored as a prognostic variable and tumor biomarker in PTCL.

Keywords: EBV; Epstein-Barr virus; PTCL; cell-free DNA; peripheral T-cell lymphoma.

Conflict of interest statement

None of the authors have a relevant conflict of interest to report.

© 2016 UICC.

Figures

Figure I. Schema of retrospectively identified PTCL patients with at least one plasma EBV-DNA (pEBVd) measurement

*pEBVd+ defined as >2000 copies/mL by a clinical qRT-PCR

Figure II. Overall survival by EBV status prior to treatment

A) Overall survival by pEBVd status prior to therapy. pEBVd+ defined as >2000 copies/mL by a clinical qRT-PCR. B) Overall survival according to EBER and pEBVd status. There were no EBER− pEBVd+ patients

Figure III. Serial pEBVd measurements before, during, and at the end of induction treatment with corresponding induction response and clinical outcomes

pEBVd measurement reported as a dichotomous variable where “+” indicated pEBVd >2000 copies/mL. Response at end of front line therapy measured in accordance with Lugano classification. pEBVd was measured at the end of induction at the same time as imaging assessment. PR=partial response, CR=complete response, PD progressive disease