Epstein-barr virus-encoded small RNA incorporated prognostic model enables precision risk stratification and guides treatment decisions in peripheral t-cell lymphoma - a multicenter retrospective cohort

Q: Why is EBER status considered important in peripheral T-cell lymphoma?

EBER reflects EBV infection and is associated with poor outcomes in PTCL. The study highlights that EBER positivity correlates with worse survival and poorer first-line chemotherapy response.

Q: How was the prognostic risk scoring system developed?

A LASSO-penalized Cox regression model was used to build a prognostic score that incorporates EBER status and multiple clinical indicators.

Q: Which factors were identified as independent adverse prognostic variables?

Albumin 250, Age>70, and EBER positivity were independently associated with poorer prognosis.

Sep 29, 2026

Uploaded by Margaret

Epstein-Barr virus-encoded small RNA (EBER), a hallmark of EBV infection, serves as a poor prognostic factor in peripheral T-cell lymphoma (PTCL), yet current clinical-based scores fail to accurately identify high-risk EBER-positive patients or meaningfully guide therapy. A multicenter retrospective cohort study analyzed 167 PTCL patients to quantify EBER-associated effects on survival and treatment response. A LASSO-penalized Cox regression yielded a risk scoring system integrating EBER status and clinical variables. After 22.1 months median follow-up, EBER positivity aligned with older age, hypoalbuminemia, higher IPI, altered immune marker positivity, and inferior chemotherapy response. Independent adverse factors included Albumin<40, Platelet-to-Monocyte Ratio≤300, Lactate Dehydrogenase>250, Age>70, and EBER positivity, stratifying patients into three distinct risk groups with significantly different overall survival.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

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Abstract

Prognostic impact and study objective

Model construction and risk stratification

Clinical implications

Annals of Hematology (2025) 104:6275–6284 [https://doi.org/10.1007/s00277-025-06683-6](https://doi.org/10.1007/s00277-025-06683-6) RESEARCH Epstein-barr virus-encoded small RNA incorporated prognostic model enables precision risk stratification and guides treatment decisions in peripheral t-cell lymphoma: a multicenter retrospective cohort Ze-Tao Chen1 · Ling Huang2 · Han-Guo Guo2 · Cai-Di Lin2 · Xin-Miao Jiang2 · Xiao-Juan Wei2 · Fei-Li Chen2 · Si-Chu Liu2 · Hong Zhang2 · Zhan-Li Liang2 · Ning Wang2 · Xiao-Dan Zhang1 · Li-E. LIN3 · Ting-Bo Liu4 · Ji-Hao Zhou5 · Zhi-Gang Peng6 · Wen-Yu Li1,2 Received: 24 August 2025 / Accepted: 1 October 2025 / Published online: 12 November 2025 © The Author(s) 2025 Abstract Epstein-Barr virus-encoded small RNA (EBER), a hallmark of EBV infection, is a poor prognostic factor in peripheral T-cell lymphoma (PTCL) . Current clinical-based prognostic scores inadequately identify high-risk EBER-positive patients or guide therapy, underscoring the need for improved risk-stratification and treatment strategies. This multicenter cohort study, encompassing 167 PTCL patients, systematically analyzed the impact of EBER status on patient survival and treatment response. Utilizing LASSO-penalized Cox regression, a novel prognostic risk scoring system was developed incorporating EBER status and clinical indicators. With a median follow-up of 22.1 months, 63 patients (38%) died. The objective response rate was 57% . EBER-positive status was associated with older age, hypoalbuminemia, high IPI scores, shorter median overall survival (mOS), higher positivity rates for CD30, CD4, BCL6, PD-1, and poorer response to first-line chemotherapy. Multivariate analysis identified independent adverse prognostic factors (p< 0.05): Albumin< 40, Platelet-to-Monocyte Ratio ≤ 300, Lactate Dehydrogenase> 250, Age > 70, and EBER-positivity. A prognostic model incorporating these factors stratified patients into three significantly distinct risk groups (p< 0.001): Low-risk (n = 45; 3-year OS 87.6%, mOS not reached), Intermediate-risk (n = 60; 3-year OS 49.7%, mOS 32.8 months), High-risk (n = 62; 3-year OS 25.1%, mOS 14.3 months) . The model outperformed existing models and demonstrated excellent discrimination, stability, clinical utility across PTCL subgroups. This novel prognostic score, integrating subtype-specific marker and clinical features, provides a refined framework for precise PTCL risk stratification and treatment guidance. Keywords Epstein-Barr virus-encoded small RNA (EBER) · PTCL · Chidamide · Chemotherapy · Prognostic model Ze-Tao Chen and Ling Huang should be considered joint first author. 􀀍 Wen-Yu Li[lwy80411@163.com](lwy80411@163.com) 1 Guangdong Provincial People’s Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, China 2 Lymphoma Division, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China 3 Department of Hematology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Hainan Province, Haikou, China 4 Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, China 5 Department of Hematology, Shenzhen People’s Hospital, Jinan University, Shenzhen, China 6 Department of Hematology, First Affiliated Hospital, Guangxi Medical University, Nanning, China Introduction Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous, aggressive group comprising 10%−15% of non-Hodgkin lymphomas. In Asia, angioimmunoblastic T-cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS) are the second and third most common subtypes (21.6–24.7% and 20.1–20.8%, respectively) [13, 37]. Most patients exhibit poor responses to chemotherapy. Despite recent improvements with optimized regimens and novel agents (e.g., CD30 monoclonal antibodies, histone deacetylase inhibitors), the 5-year overall survival (OS) remains below 3

FAQs

Why is EBER status considered important in peripheral T-cell lymphoma?

EBER reflects EBV infection and is associated with poor outcomes in PTCL. The study highlights that EBER positivity correlates with worse survival and poorer first-line chemotherapy response.

How was the prognostic risk scoring system developed?

A LASSO-penalized Cox regression model was used to build a prognostic score that incorporates EBER status and multiple clinical indicators.

Which factors were identified as independent adverse prognostic variables?

Albumin<40, Platelet-to-Monocyte Ratio≤300, Lactate Dehydrogenase>250, Age>70, and EBER positivity were independently associated with poorer prognosis.

Sep 29, 2026

Uploaded by Margaret