Clinical and Biological Cohort Study of EBV-Positive T/NK-Cell Lymphoproliferative Diseases

Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases comprise a heterogeneous spectrum of disorders that share viral and immunobiological features but differ substantially in clinical presentation, disease course, treatment, and prognosis. Extranodal NK/T-cell lymphoma is the principal disease entity in this study and will constitute the core population for clinical outcome analyses and development of integrated clinical-molecular prognostic models. The study includes two cohorts. Cohort A is a retrospective cohort of approximately 500 consecutive hospitalized patients with newly diagnosed extranodal NK/T-cell lymphoma diagnosed between January 1, 2020 and December 31, 2025. Patients are identified through pathology records, followed by clinical verification and confirmation of survival follow-up. Cohort A includes clinical data only. Cohort B is a prospective clinical-biological cohort of approximately 1,000 consecutive newly diagnosed patients enrolled between June 1, 2026 and December 31, 2030. Eligible disease entities include extranodal NK/T-cell lymphoma, aggressive NK-cell leukemia, systemic chronic active Epstein-Barr virus disease of T/NK-cell type, and Epstein-Barr virus-positive nodal T/NK-cell lymphoma. Extranodal NK/T-cell lymphoma will account for at least 80% of Cohort B. Treatment is determined by treating physicians according to routine clinical practice and is not assigned by the study. Clinical information includes baseline disease characteristics, pathology, laboratory and imaging findings, treatment exposures, response assessments, adverse events, relapse or progression, subsequent treatment, and survival. Prospective participants provide a 10-mL peripheral blood sample before treatment and are scheduled for additional sample collection after two treatment cycles, at the end of treatment or first formal end-of-treatment assessment, and at relapse or refractory disease confirmation. Plasma and peripheral blood mononuclear cells are stored in two aliquots at participating-center biobanks. Tumor tissue is optional. Molecular, viral, immune, and tumor microenvironment analyses will be performed within the scope approved by the protocol and informed consent. The main clinical outcomes are overall survival and progression-free survival. Secondary outcomes include objective response rate, complete response rate, primary refractory disease, early progression, relapse or progression patterns, post-relapse survival, grade 3 or higher adverse events, serious infections, treatment-related mortality, and longitudinal changes in plasma Epstein-Barr virus DNA, circulating tumor DNA, and immune biomarkers.