Abstract
Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) is a rare and clinically aggressive subtype of DLBCL, distinguished by its notably unfavorable prognosis. The clinical characteristics of this entity remain insufficiently characterized in the Chinese population. This study retrospectively analyzed 99 cases of EBV+DLBCL with available clinical data from Zhejiang Province, southeastern China. We comprehensively characterized the clinicopathological features of these patients and performed both univariate and multivariate survival analyses to identify independent prognostic factors. Specifically, 76.7% of patients presented with an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, 75.8% demonstrated extranodal disease involvement, and 47.5% exhibited B symptoms. Immunophenotypic analysis utilizing the Hans algorithm classified 82.8% (82/99) of cases as non-germinal center B-cell-like (non-GCB) cell-of-origin (COO). The overall survival (OS) rate was 45.4%, while the progression-free survival (PFS) rate was 30.3%. The majority of patients (71.7%, 71/99) received R-CHOP-type immunochemotherapy regimens. Both univariate and multivariate analyses identified R-CHOP-type therapy as a significant independent protective factor for both OS (P < 0.001) and PFS (P = 0.001). Multivariate analysis further revealed that hemoglobin (Hb) levels < 90 g/L, indicative of anemia, represented a potential strong adverse prognostic factor for OS, with moderate to severe anemia emerging as a clinically relevant predictor of poorer treatment outcomes. These findings underscore that EBV+DLBCL constitutes a clinically distinct lymphoma subtype associated with suboptimal outcomes under current chemoimmunotherapy. Notably, readily monitored Hb levels may serve as a practical prognostic biomarker for risk stratification in this patient population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00277-026-06912-6.