Synergistic adverse prognostic impact of CD30 and Epstein–Barr virus in peripheral T-cell lymphoma: CD30 identifies a high-risk subgroup in Epstein–Barr virus–encoded RNA -positive patients

Patients with Epstein–Barr virus–encoded RNA (EBER)-positive Peripheral T-cell lymphoma (PTCL) exhibit poor survival. Current prognostic scores lack efficacy in this group, necessitating more specific biological markers. This multicenter retrospective cohort study evaluated the prognostic significance of CD30 status in EBER-positive angioimmunoblastic T-cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS) patients. Receiver operating characteristic (ROC) analysis, Kaplan–Meier survival curves, and Cox regression analysis were employed to assess the predictive value of CD30 expression relative to conventional clinical indices. A total of 120 PTCL patients were included, among whom 47 were EBER-positive. The EBER/CD30 distribution was as follows: CD30⁻EBER⁺ 14.2% (17/120); CD30⁺EBER⁺ 25.0% (30/120); CD30⁻EBER⁻ 30.0% (36/120) and CD30⁺EBER⁻ 30.8% (37/120). The CD30⁺EBER⁺ subgroup demonstrated significantly inferior survival and treatment response, with a 3-year overall survival (OS) rate of only 6.9% (95% CI: 1.2%–37.9%), markedly lower than other subgroups (p < 0.0001). Chidamide combined with CHOP-like chemotherapy suggest a potential survival benefit in this subgroup compared to CHOP-like chemotherapy (median OS: 19.1 vs.7.3 months). Among EBER-positive PTCL patients, multivariable analysis confirmed CD30 positivity as an independent prognostic factor (p = 0.023). The 3-year AUC for CD30 was 0.742, with a sensitivity of 0.726 and specificity of 0.758, outperforming conventional clinical indicators. This multicenter cohort study identifies the CD30⁺EBER⁺ subgroup as a highly aggressive PTCL phenotype with particularly poor prognosis. CD30 positivity remains an independent risk factor, enabling the identification of a high-risk EBER-positive patient subset and providing a rationale for personalized treatment strategies.