Prospective Study of Immune Function and PD-1 Antibody Therapy Efficacy Predictors on CAEBV and EBV-HLH Patients

Capital Medical University

Status: Enrolling

Conditions: Chronic Active Epstein-Barr Virus Infection; Secondary Hemophagocytic Lymphohistiocytosis

Treatments: Other: No intervention

Study type: Observational

Funder types: Other

Identifiers

NCT05841342

BFH20221009004

Details and patient eligibility

About

This prospective case-control study aims to evaluate the immune function and find PD-1 antibody efficacy predictors on Chronic Active Epstein-Barr Virus Infection and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis by detecting lymphocyte subsets proportions in peripheral blood mononuclear cells and the positive proportion of PD-1, PD-L1 and other indicators in each lymphocyte subsets in healthy people and patients using flow cytometry before and after the initial PD-1 therapy.

Enrollment: 128 estimated patients

Sex: All

Ages: 2 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Patients who meet the diagnostic criteria of EBV-HLH or CAEBV (except B lymphocytes involvement only) after the detection of EBV lymphocyte subsets. EBV-HLH diagnostic criteria: Meet hemophagocytic lymphohistiocytosis (HLH)-04 diagnostic criteria; EBV-DNA in peripheral blood or EBER in tissue were positive, patients were diagnosed with EBV associated HLH (EBV-HLH). CAEBV diagnostic criteria: (1) persistent or recurrent infectious mononucleosis-like symptoms persisting for more than 3 months; (2) EBV-DNA quantitative increase in peripheral blood or tissue lesions; (3) exclusion of other possible Diagnosis, such as primary Epstein-Barr virus infection (infectious mononucleosis), autoimmune disease, congenital immunodeficiency, human immunodeficiency virus (HIV) infection, or other underlying conditions requiring immunosuppressive therapy or underlying immunosuppression.
2. Before the start of the study, total bilirubin ≤10 times the upper limit of normal, serum creatinine ≤1.5 times the normal value; fibrinogen can be corrected to ≥0.6g/L after infusion.
3. Serum HIV antigen or antibody negative.
4. HCV antibody negative, or HCV antibody positive, but HCV RNA negative.
5. HBV surface antigen and HBV core antibody are both negative. If any of the above is positive, peripheral blood hepatitis B virus DNA titer detection is required, and the number of copies less than 1×103 copies/ml can be included in the group.
6. LVEF ≥ 50% by cardiac echocardiography.
7. Women of childbearing age must be confirmed by a pregnancy test that they are not pregnant, and are willing to take effective contraceptive measures during the test period and within ≥ 12 months after the last dose. Women during pregnancy and lactation cannot participate. Contraceptive measures should be taken during the test period and within ≥3 months after the last dose.
8. Informed consent obtained.

Exclusion criteria

1. According to the New York Heart Association (NYHA) score, patients with heart disease of grade II or above (including grade II);
2. Pregnant or lactating women and patients of childbearing age who refused to take appropriate contraceptive measures during this trial.
3. Those who are allergic to rituximab ingredients or have more severe allergic constitution;
4. Severe hypogammaglobulinemia.
5. Active massive hemorrhage of internal organs (including gastrointestinal hemorrhage, alveolar hemorrhage, intracranial hemorrhage, etc.);
6. Uncontrolled active infection (including lung infection, intestinal infection, etc.);
7. HBV surface antigen and/or HBV core antibody are positive, and the peripheral blood hepatitis B virus DNA test confirms the existence of active hepatitis B patients.
8. Severe mental illness;
9. Patients who were not compliant during the trial and/or follow-up period.
10. Concurrently participate in other clinical investigators.

Trial design

128 participants in 2 patient groups

Healthy Control

Description:

Healthy male or female aged 2-80 years with negative EBV-DNA quantitative test results within the last week.

Treatment:

Other: No intervention

CAEBV or EBV-HLH Patients

Description:

Patients aged 2-80 years who fulfilled the diagnostic criteria for CAEBV or EBV-HLH. The diagnostic criteria for CAEBV as defined in the recently revised World Health Organization classification include persistent IM-like symptoms for more than three months, increased EBV DNA (\>10\^2.5 copies/mg) in peripheral blood, histological evidence of organ disease, and EBV RNA or viral protein in affected tissues. Patients diagnosed with EBV-HLH must meet five of the following eight HLH-2004 diagnostic criteria: 1. temperature 38.5 ℃ and above; 2. splenomegaly; 3. two or three lines of hemocytopenia, i.e. hemoglobin (HB) \<90 g/L, platelets (PLT) \<100 × 10\^9/L or neutrophils (N) \<1 × 10\^9/L; 4. triacylglycerol (TG) ≥ 3 mmol/ L or fibrinogen (Fbg) \<1.5 g/L; 5. serum ferritin (SF) ≥ 500 mg/L; 6. phagocytosis found in bone marrow, spleen, liver or lymph nodes; 7. soluble CD25 (sCD25) ≥ 2400 U/mL; 8. low or absent natural killer (NK) cell activity.

Treatment:

Other: No intervention