Ex vivo expansion and prophylactic infusion of CMV-pp65 peptide-specific cytotoxic T-lymphocytes following allogeneic hematopoietic stem cell transplantation

Biol Blood Marrow Transplant. 2007 Jun;13(6):707-14. doi: 10.1016/j.bbmt.2007.02.004. Epub 2007 Apr 6.


Cytomegalovirus reactivation and infection post-allogeneic hematopoietic stem cell transplant continue to cause morbidity and mortality. Current pharmacologic therapies are limited by side effects. Adoptive transfer of ex vivo generated cytomegalovirus-specific T cells has the potential to restore immunity, prevent cytomegalovirus, and circumvent the need for pharmacologic therapies. We have generated donor-derived cytomegalovirus-specific cytotoxic T cells using dendritic cells pulsed with the HLA-A2 restricted nonapeptide NLVPMVATV (NLV) derived from the cytomegalovirus-pp65 protein. These cytotoxic T cells have been given prophylactically to 9 recipients aged 4 to 65 years on or after day 28 post-allogeneic hematopoietic stem cell transplant. Only 2 of 9 recipients received T cell depletion in vivo or in vitro. There were no immediate adverse reactions to the infusions. During 97-798 days of follow-up, 2 recipients developed cytomegalovirus reactivation; neither developed cytomegalovirus disease or required pharmacotherapy. Three recipients developed acute graft versus host disease after infusion. Two recipients died, 1 from thrombotic thrombocytopenia purpura secondary to cyclosporine, 1 from complications of graft versus host disease. A transient increase in numbers of cytomegalovirus-specific T cells demonstrated by NLV-tetramer binding was seen in 6 recipients. Prophylactic adoptive transfer of NLV-specific T cells is safe and may be effective in preventing cytomegalovirus reactivation.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adoptive Transfer / adverse effects
  • Adoptive Transfer / methods*
  • Adult
  • Aged
  • Cell Culture Techniques
  • Child
  • Child, Preschool
  • Cytomegalovirus Infections / prevention & control*
  • Dendritic Cells / cytology
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Lymphocyte Transfusion / adverse effects
  • Lymphocyte Transfusion / methods
  • Male
  • Middle Aged
  • Phosphoproteins / therapeutic use
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / transplantation*
  • Transplantation, Homologous
  • Treatment Outcome
  • Viral Matrix Proteins / therapeutic use
  • Virus Activation


  • Phosphoproteins
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa