Prognostic role of whole blood Epstein‑Barr virus DNA load in angioimmunoblastic T-cell lymphoma.

[OBJECTIVE] The prognostic role of Epstein-Barr virus (EBV) DNA in aggressive angioimmunoblastic T-cell lymphoma (AITL) remains unclear. This study aimed to investigate the prognostic significance of whole blood EBV DNA at diagnosis in AITL patients, establish an optimal prognostic cutoff, and develop a novel prognostic index incorporating this viral biomarker.

[METHODS] This multicenter retrospective study included 323 newly diagnosed AITL patients. The optimal cutoff of EBV DNA was determined using maximally selected rank statistics. Independent prognostic factors identified by multivariate Cox regression were used to construct a novel prognostic index (AITL prognostic index [API]), which was internally validated and compared with existing models.

[RESULTS] At diagnosis, 241 (74.6%) AITL patients were EBV DNA positive, with 143 (44.3%) exceeding the optimal cutoff for EBV DNA load of 6110 copies/mL. EBV DNA > 6110 copies/mL was established as an independent adverse factor for overall survival (HR, 1.553; =.006), along with age ≥ 60 years, ECOG ≥ 2, platelets < 150 × 10/L, and extranodal sites > 1. Based on these thresholds, API was used to stratify patients into four distinct risk groups with significantly different median OS ( <.001) and demonstrated superior discriminatory power (Harrell’s C-statistic: 0.741; Akaike Information Criterion value: 1829.1) compared to IPI, PIT, PIAI, and AITL score.

[CONCLUSIONS] Whole blood EBV DNA load is a powerful, independent prognostic index in AITL. The novel prognostic index API integrates a quantitative EBV DNA cutoff, providing superior risk stratification over established prognostic models, and guideing clinical decision-making for AITL patients.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s13027-026-00739-6.