Worldwide experience of chronic active EBV infection: Retrospective cohort study.

Abstract

7016 Background: Chronic active Epstein-Barr virus disease (CAEBV) is a rare, life-threatening disorder characterized by systemic inflammation and clonal proliferation of EBV-infected T or NK cells. The disease exhibits clinical variability, ranging from mild to rapidly progressive and fatal forms. Despite advances in understanding its features, most studies are based on small cohorts or case reports, with no standardized diagnostic or therapeutic guidelines. Regional differences in age distribution, clinical characteristics, and treatment strategies exist. This study analyzed 763 CAEBV cases to summarize global experiences and propose a new classification and risk stratification model. Methods: This retrospective cohort study analyzed 763 CAEBV cases from 57 centers across 9 countries, including data from a systematic review and institutional data from Tongji Hospital, Wuhan, China. A novel classification system and risk stratification model were developed based on clinical and pathological data. Treatment outcomes, including allo-HSCT, anti-PD-1 therapy, and chemotherapy, were evaluated using survival analysis and multivariate Cox regression. Results: Among the 763 cases, 98.1% were from East Asia (China 53%, Japan 41%, Korea 4%), with smaller contributions from America (2%) and other countries. The median age at diagnosis was 18 years, with 53.7% of cases in those under 20. EBV-infected T cells were seen in 52% of cases, NK cells in 38%, and mixed infections in 10%. A new classification system divided systemic CAEBV (sCAEBV) into four subtypes: cutaneous (10%), gastrointestinal (4.6%), vascular (3.2%), and not otherwise specified (82.2%). Gastrointestinal involvement was associated with the poorest prognosis, necessitating early intervention. Treatment data from 399 patients showed that allo-HSCT is the only curative option, significantly improving survival rates. For high-risk patients unable to undergo allo-HSCT, anti-PD-1 therapy showed potential as an adjunctive treatment. A risk stratification model categorized patients into low-risk, high-risk, and very high-risk groups. Low-risk patients were monitored and treated with anti-PD-1 therapy, high-risk patients received either anti-PD-1 therapy or allo-HSCT, and very high-risk patients were advised to undergo allo-HSCT. Conclusions: This study represents the largest global cohort of CAEBV cases, with 763 cases from 9 countries. A novel classification system for sCAEBV was proposed, highlighting gastrointestinal involvement as a poor prognostic factor. Based on clinical symptoms and laboratory findings, a new risk stratification model was developed, guiding personalized treatment. Allo-HSCT remains the only curative treatment, significantly improving survival, while anti-PD-1 therapy offers potential as an adjunctive treatment for high-risk patients who cannot undergo allo-HSCT.