Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation

Blood. 2009 Nov 5;114(19):4283-92. doi: 10.1182/blood-2009-07-232454. Epub 2009 Aug 21.


Viral infection or reactivation remains a major cause of morbidity and mortality after allogeneic stem cell transplantation. We now show that infusions of single cytotoxic T lymphocyte (CTL) lines (5 x 10(6)-1.35 x 10(8) cells/m(2)) with specificity for 2 commonly detected viruses, Epstein-Barr virus (EBV) and adenovirus, can be safely administered to pediatric transplantation recipients receiving partially human leukocyte antigen-matched and haploidentical stem cell grafts (n = 13), without inducing graft-versus-host disease. The EBV-specific component of the CTLs expanded in vivo and persisted for more than 12 weeks, but the adenovirus-specific component only expanded in vivo in the presence of concomitant adenoviral infection. Nevertheless, adenovirus-specific T cells could be detected for at least 8 weeks in peripheral blood, even in CTL recipients without viral infection, provided the adenovirus-specific component of their circulating lymphocytes was first expanded by exposure to adenoviral antigens ex vivo. After infusion, none of these 13 high-risk recipients developed EBV-associated lymphoproliferative disease, while 2 of the subjects had resolution of their adenoviral disease. Hence, bispecific CTLs containing both EBV- and adenovirus-specific T cells can safely reconstitute an antigen responsive "memory" population of CTLs after human leukocyte antigen-mismatched stem cell transplantation and may provide antiviral activity. This trial was registered at as #NCT00590083.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus Infections, Human / etiology
  • Adenovirus Infections, Human / immunology
  • Adenovirus Infections, Human / prevention & control*
  • Adenovirus Infections, Human / therapy*
  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / isolation & purification
  • Adolescent
  • Cell Line
  • Child
  • Child, Preschool
  • DNA, Viral / genetics
  • DNA, Viral / isolation & purification
  • Epstein-Barr Virus Infections / etiology
  • Epstein-Barr Virus Infections / immunology
  • Epstein-Barr Virus Infections / prevention & control*
  • Epstein-Barr Virus Infections / therapy*
  • Female
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification
  • Histocompatibility Testing
  • Humans
  • Immunologic Memory
  • Immunotherapy, Adoptive
  • Infant
  • Lymphocyte Depletion
  • Male
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / transplantation*
  • Tissue Donors
  • Transplantation, Homologous


  • DNA, Viral

Associated data