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

Summary

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.