Background: Chronic active Epstein-Barr virus infection (CAEBV) is a rare and potentially fatal lymphoproliferative disorder characterized by persistent systemic inflammation and clonal expansion of EBV-infected T or NK cells. While global analyses such as those presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting have shed light on the clinical spectrum of CAEBV, pronounced geographic and ethnic disparities, particularly the substantially higher incidence in East Asia, highlight the need for region-specific investigation. Previous international cohorts, often composed of mixed populations, have not fully captured the distinct clinical phenotypes, organ involvement patterns, therapeutic responses, and prognostic outcomes of East Asian patients. This study addresses this gap by focusing on a large, representative cohort of East Asian individuals with the aim of informing tailored diagnostic and therapeutic strategies. Methods: A total of 568 East Asian patients with CAEBV were enrolled from 49 centers, representing the largest multicenter cohort of this population to date. Comprehensive patient-level data were collected through systematic literature review and retrospective institutional analysis. Clinical features, treatment modalities, risk factors, and survival outcomes were meticulously evaluated. Results: For the first time, an organ-based classification system was established for CAEBV within the Asian population, categorizing patients as cutaneous (17.24%), vascular (7.4%), gastrointestinal (6.6%), or not otherwise specified (NOS, 68.76%). Compared to international cohorts, Asian patients exhibited notably higher rates of cutaneous and gastrointestinal involvement, alongside a moderate increase in the vascular subtype. Three-year overall survival (OS) varied significantly among subtypes, with the cutaneous group demonstrating the most favorable prognosis (88.6%), followed by vascular (75.1%), NOS (73.2%), and gastrointestinal (31.5%). Notably, the gastrointestinal subtype was associated with markedly poorer survival compared to previous studies, further highlighting the heterogeneity of outcomes based on organ involvement in this population. In patients who did not undergo hematopoietic stem cell transplantation (HSCT), PD-1 inhibitor therapy yielded encouraging results, with a three-year OS of 91.7%. To facilitate individualized risk assessment, a three-tiered risk stratification model was developed, incorporating serum soluble CD25 (>5600 pg/mL), ferritin (>398 µg/L), and gastrointestinal involvement. This model reliably identified low-risk patients unlikely to require allogeneic transplantation, as well as high- and very high-risk groups who may benefit from PD-1 blockade, thereby supporting more personalized therapeutic decisions. Conclusion: In summary, this study establishes a clinically meaningful organ-based classification and risk-adapted management framework for CAEBV in East Asian patients. These findings enhance understanding of disease heterogeneity in this region and provide valuable guidance for optimizing treatment strategies and improving patient outcomes.

This content is only available as a PDF.
2025
Sign in via your Institution