This study is a prospective, multicenter, single-arm clinical trial designed to evaluate the efficacy and safety of PD-1 inhibitor combined with tenofovir, chidamide, and lenalidomide in the treatment of relapsed or refractory Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs). The primary endpoint is the overall response rate (ORR) at 3 months, including complete response (CR) and partial response (PR). Secondary endpoints include overall survival (OS), progression-free survival (PFS), as well as safety and tolerability assessments. Eligible patients must have histologically confirmed EBV-positive B-cell or T/NK-cell LPDs with measurable lesions. This combination regimen targets multiple mechanisms, including inhibition of EBV replication, activation of the immune system, and enhancement of antitumor effects, aiming to provide an innovative therapeutic strategy for this challenging disease.

Inclusion Criteria:

1. Histologically confirmed EBV-associated lymphoproliferative disorders, including EBV-positive B-cell LPD and EBV-positive T/NK-cell LPD, with EBV-encoded RNA (EBER)+ by in situ hybridization, or EBV nuclear antigen (EBNA)+, or latent membrane protein (LMP1/2)+ in the lesion tissue.
2. Age ≤75 years with an ECOG performance status ≤2.
3. At least one bidimensionally measurable lesion for evaluation: for nodal lesions, longest diameter ≥1.5 cm and shortest diameter ≥1.0 cm; for extranodal lesions, longest diameter ≥1.0 cm; or ≥20% monoclonal EBV-infected lymphocytes detected by flow cytometry.
4. Expected survival of more than 3 months.
5. Ability to comply with follow-up. Patients must be aware of the nature of their disease and voluntarily agree to participate in the study and follow-up.

Exclusion Criteria:

1. Patients with impaired liver or kidney function, defined as serum direct bilirubin, indirect bilirubin, and/or ALT, AST, or serum creatinine levels >2 times the upper limit of normal, unless deemed lymphoma-related.

2. Patients with bone marrow failure, defined as absolute neutrophil count (ANC) <1.5×10⁹/L or platelets <75×10⁹/L, unless the hematologic abnormalities are considered due to bone marrow infiltration by lymphoma.

3. Patients who have experienced grade ≥3 neurotoxicity within the past 2 weeks.

4. Patients with chronic heart failure classified as NYHA Class III or IV, or with left ventricular ejection fraction <50%, or with a history within the past 6 months of any of the following: acute coronary syndrome, acute heart failure (Class III or IV), or significant ventricular arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, or post-resuscitation sudden cardiac arrest).

5. Patients with AIDS, syphilis, or active hepatitis B (HBV DNA >1×10⁴ copies/ml) or active hepatitis C infection.

6. Patients diagnosed with malignancies other than lymphoma or currently undergoing treatment for other cancers, except:

   ① Those who have received curative treatment and have been disease-free for ≥5 years prior to enrollment;

   ② Patients with adequately treated, non-melanoma skin cancers such as basal cell carcinoma without evidence of disease;

   ③ Patients with adequately treated carcinoma in situ of the cervix without evidence of disease.

7. Patients with other hematologic diseases (e.g., hemophilia, myelofibrosis) considered unsuitable for the study by the investigator.

8. Patients with severe active infections.

9. Patients who underwent Grade 2 or higher surgery within 3 weeks before treatment initiation.

10. Patients with a history of substance abuse, or medical, psychological, or social conditions that may interfere with study participation or evaluation, as judged by the investigator.

11. Any other condition the investigator considers unsuitable for study enrollment.

12. Known hypersensitivity to any component of the investigational drugs.