Application of PD-1 Inhibitors, Tenofovir, Chidamide, and Lenalidomide in Relapsed/Refractory EBV-associated Lymphoproliferative Disorders.

Inclusion criteria

• 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.
• Age ≤75 years with an ECOG performance status ≤2.
• 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.
• Expected survival of more than 3 months.
• 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

• 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.
• 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.
• Patients who have experienced grade ≥3 neurotoxicity within the past 2 weeks.
• 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).
• Patients with AIDS, syphilis, or active hepatitis B (HBV DNA >1×10⁴ copies/ml) or active hepatitis C infection.
• 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.

• Patients with other hematologic diseases (e.g., hemophilia, myelofibrosis) considered unsuitable for the study by the investigator.
• Patients with severe active infections.
• Patients who underwent Grade 2 or higher surgery within 3 weeks before treatment initiation.
• 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.
• Any other condition the investigator considers unsuitable for study enrollment.
• Known hypersensitivity to any component of the investigational drugs.