Original Article

Bone Marrow Transplantation (2007) 39, 293–299. doi:10.1038/sj.bmt.1705585; published online 29 January 2007

Post-Transplant Events

Patients at high risk for CMV infection and disease show delayed CD8+ T-cell immune recovery after allogeneic stem cell transplantation

S Ganepola1, C Gentilini1, U Hilbers2, T Lange2, K Rieger1, J Hofmann3, M Maier4, U G Liebert4, D Niederwieser2, E Engelmann5, R Heilbronn5, E Thiel1 and L Uharek1

  1. 1Department of Internal Medicine III, Charité, Campus Benjamin Franklin, Hindenburgdamm, Berlin, Germany
  2. 2Department of Internal Medicine, Division of Hematology and Oncology, University Hospital Leipzig, Johannisallee, Leipzig, Germany
  3. 3Institute of Virology, Charite, Berlin, Germany
  4. 4Institute of Virology, University of Leipzig, Johannisallee, Leipzig, Germany
  5. 5Department of Virology, Charite, Campus Benjamin Franklin, Hindenburgdamm, Berlin, Germany

Correspondence: Dr S Ganepola, Department of Internal Medicine III, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: susanne.ganepola@charite.de

Received 10 May 2006; Revised 11 December 2006; Accepted 15 December 2006; Published online 29 January 2007.

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Abstract

Human cytomegalovirus (CMV) is a major cause of death after transplantation. The frequency of pp65-specific T cells was examined in 38 HLA-A2+ stem cell recipients during the first year after transplantation. Patients were divided into four groups based on donor/recipient serostatus: d+/r+ (n=17), d+/r- (n=7), d-/r+ (n=9) and d-/r- (n=5). Peripheral blood mononuclear cells were stimulated with the CMVpp65 peptide NLVPMVATV, and the specific T-cell frequency was assessed by interferon gamma (IFN-italic gamma) ELISPOT assay. Responding T cells were characterized by flow cytometry revealing a terminal differentiated effector phenotype. Surveillance of CMV infection was carried out by real-time polymerase chain reaction (n=26) or immunofluorescence (n=12). Infection was present in 7/9 d-/r+ high-risk patients, and CMV disease occurred exclusively in this group with delayed or absent virus-specific T-cell recovery. In contrast, 16/24 intermediate-risk patients showed CMV-specific T cells. Our data suggest that CMV infection and disease rates are elevated in high-risk patients with delayed CMV-specific T-cell immune reconstitution and lower in those with early recovery of T-cell immunity. We recommend preferring CMV seropositive donors for CMV seropositive recipients, as this should lead to durable CMV-specific T-cell responses soon after transplantation with consecutive protection from CMV disease.

Keywords:

allogeneic stem cell transplantation, T-cell immune recovery, CMV infection, CMV-specific T cells

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