L-DEP Regimen Combined With PD-1 Antibody as Induction Therapy for Epstein-Barr Virus-positive LA-HLH

Lymphoma-associated hemophagocytic lympohistiocytosis is a refractory immune disorder with high mortality. Without early intervention, the median survival time is less than 2 months. Currently, HLH-94 or HLH-04 are the standard HLH treatment regimens, which have improved the disease response rate to approximately 70% and increased the 5-year OS rate to 50%. However, approximately, 30% of the patients remain unresponsive to standard therapy, especially if HLH is lymphoma-associated. Therefore, we conduct a prospective clinical study to explore the efficacy and safety of L-DEP (PEG-aspargase, liposomal doxorubicin, etoposide, and methylprednisolone) regimen combined with PD-1 Antibody an induction therapy for Epstein-Barr virus (EBV)-positive lymphoma-associated hemophagocytic lymphohistiocytosis.

Inclusion criteria

• Diagnosed as lymphoma-Hemophagocytic Lymphohistiocytosis.
• EBV-DNA in peripheral blood > 1000 copies/ml or EBER detected in tissue specimens.
• Age 18~65，gender is not limited.
• Estimated survival time ≥ 1 month.
• Cardiac ultrasound LVEF≥50%; No Active bleeding of the internal organs(digestive tract, lung, brain, etc.); If the patient has dyspnea, oxygenation index >250.
• Signed informed consent.

Exclusion criteria

• Heart function above grade II (NYHA).
• Severe myocardial injury：TNT、TNI、CK-MB > 3 ULN.
• Accumulated dose of doxorubicin above 400mg/m2 、epirubicin above 750mg/m2、pirarubicin above 800mg/m2 or the patients treated with anthracycline induced cardiovascular disease.
• Pregnancy or lactating Women.
• Allergic to pegylated liposomal doxorubicin，etoposide，or PD-1 antibody.
• Thyroid dysfunction.
• HIV antibody positivity.
• Acute or chronic active hepatitis B (HBsAg positivity, HBV DNA negative acceptable), acute or chronic active hepatitis C (HCV antibody negatively acceptable; HCV antibody positivity, HCV RNA negative acceptable).
• Participate in other clinical research at the same time.
• The researchers considered that patients are not suitable for the study.