Aggressive NK-Cell Leukemia, Epstein-Barr Virus-Positive Nodal T/NK-Cell Lymphoma, Epstein-Barr Virus-Positive T/NK-Cell Lymphoproliferative Disease, Extranodal NK/T-cell Lymphoma, Systemic Chronic Active Epstein-Barr Virus Disease
Conditions
Keywords
Epstein-Barr virus, T/NK-cell lymphoproliferative disease, extranodal NK/T-cell lymphoma, aggressive NK-cell leukemia, chronic active Epstein-Barr virus disease, EBV-positive nodal T/NK-cell lymphoma, circulating tumor DNA, plasma EBV-DNA, immune profiling, molecular biomarker
Brief summary
This is a multicenter, non-interventional, ambidirectional cohort study of Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases. The study consists of a retrospective clinical cohort of 500 consecutively diagnosed patients with extranodal NK/T-cell lymphoma and a prospective clinical-biological cohort of 1,000 newly diagnosed patients with extranodal NK/T-cell lymphoma, aggressive NK-cell leukemia, systemic chronic active Epstein-Barr virus disease of T/NK-cell type, or Epstein-Barr virus-positive nodal T/NK-cell lymphoma. The study will characterize clinical features, treatment pathways, response, relapse or progression patterns, and long-term survival. The prospective cohort will additionally undergo standardized collection of peripheral blood and optional tumor tissue specimens at predefined clinical time points. Clinical, molecular, viral, and immune biomarkers will be evaluated for their associations with treatment response, treatment failure, disease progression, and survival. No treatment is assigned by the study.
Detailed description
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.
Interventions
None listed
Sponsors
Rong Tao
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older. * Newly diagnosed Epstein-Barr virus-positive T/NK-cell lymphoproliferative disease meeting World Health Organization diagnostic criteria. * For the retrospective cohort: diagnosis of extranodal NK/T-cell lymphoma between January 1, 2017 and December 31, 2025 at a participating center. * For the prospective cohort: diagnosis between June 1, 2026 and December 31, 2030 of one of the following: * Extranodal NK/T-cell lymphoma; * Aggressive NK-cell leukemia; * Systemic chronic active Epstein-Barr virus disease of T/NK-cell type; or Epstein-Barr virus-positive nodal T/NK-cell lymphoma. * Availability of essential diagnostic, staging, and treatment information. * For the prospective cohort: written informed consent and successful collection of the protocol-required baseline peripheral blood specimen.
Exclusion criteria
* For the retrospective cohort: no usable survival follow-up information, inability to confirm survival status, or inability to calculate the principal survival outcomes. * For the prospective cohort: unwillingness or inability to participate in protocol-defined longitudinal clinical follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From initial diagnosis to death or last confirmed follow-up, assessed for up to 10 years. | Overall survival is defined as the time from the date of initial diagnosis to death from any cause. Participants who are alive will be censored at the date on which their survival status was last confirmed. |
| Progression-Free Survival | From initial diagnosis to progression, relapse, death, or last disease assessment, assessed for up to 10 years. | Progression-free survival is defined as the time from the date of initial diagnosis to the first documented disease progression, disease relapse, or death from any cause, whichever occurs first. Participants without an event will be censored at the date of the last assessment confirming absence of progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | From initiation of first-line treatment through the first-line end-of-treatment assessment, assessed for up to 24 months. | The proportion of response-evaluable participants who achieve a best response of complete response or partial response during first-line treatment. The response-evaluable population includes participants who undergo at least one formal response assessment. |
| Complete Response Rate | From initiation of first-line treatment through the first-line end-of-treatment assessment, assessed for up to 24 months. | The proportion of response-evaluable participants who achieve complete response during first-line treatment. |
| Grade 3 or Higher Adverse Events | During each treatment line, from treatment initiation through treatment completion, assessed for up to 24 months per treatment line. | The proportion of participants experiencing grade 3 or higher adverse events during systemic anticancer treatment, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. |
| Treatment-Related Mortality | From initiation of first anticancer treatment to 30 days after the last administered treatment, assessed for up to 10 years across treatment lines. | The proportion of participants whose death is assessed as related to anticancer treatment. |
Countries
China
Contacts
CONTACTRong Tao, MD
CONTACTChuanxu Liu, MD
Outcome results
None listed