Early Experience With CliniMACS Prodigy CCS (IFN-gamma) System in Selection of Virus-specific T Cells From Third-party Donors for Pediatric Patients With Severe Viral Infections After Hematopoietic Stem Cell Transplantation

J Immunother. 2018 Apr;41(3):158-163. doi: 10.1097/CJI.0000000000000197.

Abstract

Viral reactivation is a frequent complication of allogeneic hematopoietic stem cell transplantation especially in children. For refractory cases, rapid virus-specific T-cell therapy would be ideally implemented within a few days. Over the course of a year in our pediatric cohort of 43 allogeneic transplantation, 9 patients fulfilled criteria for virus-specific T-cell therapy. Viral infections were due to cytomegalovirus (CMV) in 3, Epstein-Barr virus (EBV) in 2, and adenovirus (AdV) in 1 case, whereas >1 virus was detected in 3 cases. Viral diseases necessitating a T-cell therapy were CMV pneumonitis and colitis, AdV enteritis and cystitis, and EBV-induced posttransplantation lymphoproliferative disease. Cells were produced by the CliniMACS Prodigy CCS (IFN-gamma) System within 24 hours after mononuclear leukapheresis. Eight patients became completely asymptomatic, whereas 7 also cleared the virus. Six patients are alive without viral illness or sequelae demonstrating viral DNA clearance in peripheral blood with a median follow-up of 535 (350-786) days. One patient with CMV pneumonitis died of respiratory insufficiency. In 2 cases the viral illness improved or cleared, however, the patients died of invasive aspergillosis. No cases of graft-versus-host disease, rejection, organ toxicity, or recurrent infection were noticed. Virus-specific T-cell therapy implemented by the CliniMACS Prodigy CCS (IFN-gamma) System is an automated, fast, safe, and probably effective way to control resistant viral diseases after pediatric hematopoietic stem cell transplantation.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Child
  • Child, Preschool
  • Cytokines / metabolism
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunotherapy, Adoptive
  • Infant
  • Male
  • Middle Aged
  • T-Cell Antigen Receptor Specificity*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tissue Donors
  • Transplantation, Homologous
  • Viral Load
  • Virus Diseases / diagnosis
  • Virus Diseases / etiology*
  • Virus Diseases / therapy

Substances

  • Antiviral Agents
  • Cytokines