Treatment of pediatric refractory or relapsed Epstein-Barr virus-associated hemophagocytic syndrome with PD-1 inhibitors

Pediatr Blood Cancer. 2024 Dec;71(12):e31340. doi: 10.1002/pbc.31340. Epub 2024 Sep 27.

Abstract

Purpose: Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a type of pediatric HLH that occurs frequently in Asia. Although immunochemotherapy based on etoposide and hormone has improved survival rates, there are still about 30% of HLH patients that do not respond. The objective of the article is to examine the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors for children with relapsed/refractory (r/r) EBV-HLH.

Methods: A retrospective case note review of four pediatric patients with r/r EBV-HLH who were treated with PD-1 inhibitors at Sun Yat-sen Memorial Hospital, Sun Yat-sen University.

Results: All four patients responded to PD-1 inhibitors and achieved partial response after their first infusion. Plasma EBV DNA copy number and HLH-related monitoring indicators decreased in all of these patients. All patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and two were still alive at the last follow-up on December 30, 2022. Two patients died because of transplantation-related complications. Serious side effects included increased liver enzymes and edema in two patients.

Conclusion: PD-1 inhibitors are an effective salvage therapy and can provide a bridge to allo-HSCT for pediatric patients with r/r EBV-HLH. However, side effects should be monitered.

Keywords: Epstein–Barr virus; children; hemophagocytic lymphohistiocytosis; programmed cell death protein 1 inhibitors.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Epstein-Barr Virus Infections* / complications
  • Epstein-Barr Virus Infections* / drug therapy
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation
  • Herpesvirus 4, Human* / isolation & purification
  • Humans
  • Immune Checkpoint Inhibitors* / adverse effects
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Lymphohistiocytosis, Hemophagocytic* / drug therapy
  • Lymphohistiocytosis, Hemophagocytic* / mortality
  • Male
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Recurrence
  • Retrospective Studies

Substances

  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor
  • PDCD1 protein, human