Prognostic impact of blood Epstein-Barr virus-DNA in patients with peripheral T-cell lymphoma, not otherwise specified.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is a heterogeneous nodal T- and natural killer (NK)-cell lymphoma with limited prognostic biomarkers. A subset of PTCL-NOS characterized by Epstein-Barr virus (EBV) involvement in tumour cells has recently been recognized as EBV-positive nodal T- and NK-cell lymphoma (EBV+ nPTCL), a distinct entity in the fifth edition of the World Health Organization classification of haematolymphoid neoplasms (WHO-HAEM5). However, the clinical significance of circulating EBV deoxyribonucleic acid (DNA) in PTCL-NOS remains unclear. Patients initially diagnosed with PTCL-NOS who received first-line systemic chemotherapy at a single-centre between 2007 and 2025 were retrospectively analysed. Cases were reclassified according to WHO-HAEM5 using EBV-encoded small ribonucleic acid (EBER) in situ hybridization and pathological review. Among 101 patients, 4 were reclassified as EBV+ nPTCL using a ≥50% tumour cell EBER positivity cut-off and excluded, yielding a cohort of 97 patients with WHO-HAEM5-defined PTCL-NOS. Baseline blood EBV-DNA positivity was observed in 42.3%. EBV-DNA-positive patients demonstrated significantly shorter progression-free and overall survival (OS) compared with EBV-DNA-negative patients. In multivariate analyses, EBV-DNA positivity independently predicted poorer survival outcomes. Exploratory analyses indicated that EBV-DNA clearance during chemotherapy was associated with improved OS. These findings suggest that blood EBV-DNA may serve as a prognostic biomarker in patients with PTCL-NOS.