EBV-HLH and CAEBV are both caused by EBV infection, part of them can rapidly lead to a syndrome of severe, life-threatening hyper-inflammation, with poor prognosis. Currently, the most effective treatment remains unknown. This study is trying to evaluate the efficacy and safety of PD-1 monoclonal antibody as a first-line therapy for EBV-HLH and CAEBV.

Eligible patients who were diagnosed with EBV-HLH or CAEBV, age between 12 and 70 years, were enrolled in this study. All of them need to sign the informed consent first.

PD-1 monoclonal antibody 200mg is infused intravenously once for patients whose age >=18 years, or age <18 years but weight >=40kg. While for patients age <18 years, the dose of PD-1 monoclonal antibody is 3mg/kg. Besides, optimal supportive care is necessary.

Ruxolitinib and/or low-dose glucocorticoid can be used to reduce inflammation.

Cerebrospinal fluid parameters are examined, and methotrexate 15mg combined with dexamethasone will be intrathecal injected without contraindications.

Clinical and laboratory indicators are investigated weekly to evaluate the efficacy and toxicity.

If patients achieve partial response/complete response within 14 days after PD-1 monoclonal antibody, the clinical observations are stopped. If not, the observation period is prolonged to 21 days.

If disease progress at day 21, this study is terminated, and the patient should be transfer to other treatments as soon as quickly.

Inclusion Criteria:

1. Meet the diagnostic criteria of EBV-HLH or CAEBV.
2. Newly diagnosed patients.
3. Eastern Cooperative Oncology Group score 0-3.
4. Total bilirubin <= 10 times of upper limit of normal (except for those caused by EBV-HLH or CAEBV), and serum creatinine <= 1.5 times of upper limit of normal.
5. Serum HIV antigen or antibody is negative.
6. Hepatitis C virus (HCV) antibody is negative, or HCV antibody is positive, but HCV-RNA is negative.
7. Both HbsAg and HbcAb for Hepatitis B virus (HBV) are negative. If not, the quantification of HBV-DNA needs to be <1*10e3 IU/ml.
8. The patient or his/her guardian must be able to understand and be willing to participate in this study, and sign the informed consent.

Exclusion Criteria:

1. Non EBV-HLH or CAEBV patients.
2. Refractory or relapsed EBV-HLH or CAEBV.
3. Heart function above grade II (NYHA).
4. Patients suffered from other uncontrollable active infections.
5. Pregnant or lactating women.
6. Patients with mental disorders and cannot cooperate with the requirements of research, treatment and monitoring.
7. Active visceral bleeding.
8. Allergic to PD-1 monoclonal antibody.
9. Patients with known autoimmune diseases.
10. Participate in other clinical research at the same time.
11. The investigator judges that the patient has other reasons not suitable for this study, or participating in the study will bring great risks to the patient.