EBV-directed viral-specific T-lymphocyte therapy for the treatment of EBV-driven lymphoma in two patients with primary immunodeficiency and DNA repair defects

Pediatr Blood Cancer. 2020 Mar;67(3):e28126. doi: 10.1002/pbc.28126. Epub 2019 Dec 18.

Abstract

Children with ataxia telangiectasia (AT), a primary immunodeficiency caused by mutations in ATM, which is critical for repairing DNA defects, are at risk for the development of hematologic malignancy, frequently driven by infection with Epstein-Barr virus (EBV). Conventional chemotherapy is poorly tolerated by patients with AT, with excessive toxicity even when doses are reduced. Here, we report on two patients with AT and EBV-positive neoplasms who were treated with EBV-targeted viral-specific T cells (VST). One patient had a prolonged complete response to VSTs while the other had a partial response. Therapy was well tolerated without infusion toxicity or graft-versus-host disease.

Keywords: DNA repair defect; Epstein-Barr virus; cellular therapy; immunodeficiency; lymphoma.

Publication types

  • Case Reports

MeSH terms

  • Ataxia Telangiectasia / etiology
  • Ataxia Telangiectasia / pathology
  • Ataxia Telangiectasia / therapy*
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Child
  • DNA Damage
  • DNA Repair / genetics*
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Herpesvirus 4, Human / genetics*
  • Hodgkin Disease / etiology
  • Hodgkin Disease / pathology
  • Hodgkin Disease / therapy*
  • Humans
  • Immunotherapy / methods
  • Infant
  • Male
  • Mutation
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / etiology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prognosis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Virus Activation

Substances

  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins