Impact of viral reactivations in the era of pre-emptive antiviral drug therapy following allogeneic haematopoietic SCT in paediatric recipients

Bone Marrow Transplant. 2013 Jun;48(6):803-8. doi: 10.1038/bmt.2012.221. Epub 2012 Nov 26.


While pre-emptive rituximab therapy for EBV has substantially reduced the incidence of post-transplant lymphoproliferative disorder, following allogeneic haematopoietic SCT (HSCT), cytomegalovirus (CMV) and adenovirus (ADV) still contribute to significant morbidity and mortality after HSCT. We therefore aimed to identify high-risk children who could benefit from recent advances in virus-specific immunotherapy, define the impact of viral reactivations on survival and estimate the economic burden of pre-emptive antiviral drug therapy. Between 2005 and 2010, prospective monitoring of 291 paediatric HSCT procedures revealed that reactivation of CMV (16%), ADV (15%) and EBV (11%) was frequent during period of CD4 T-cell lymphopenia (0.15 × 10(9) L(-1); P<0.05). We report significant risk factors for reactivation, most notably the use of serotherapy and development of GVHD (grade II) in the presence of pre-existing infection (ADV) or donor and/or recipient seropositivity (CMV, EBV). Most interestingly, CMV and ADV viraemia were the major independent predictors of mortality (P<0.05). CMV, ADV or EBV viral reactivation caused prolonged hospitalization (P<0.05), accounted for 15% of all mortality and substantially increased the cost of transplantation by ∼£22 500 ($34 000). This provides an economic rationale for targeting high-risk HSCT recipients with interventions such as virus-specific cell therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Allografts
  • CD4-Positive T-Lymphocytes / immunology
  • Child
  • Child, Preschool
  • DNA Virus Infections / immunology
  • DNA Virus Infections / mortality*
  • DNA Viruses*
  • Female
  • Genetic Diseases, Inborn / immunology
  • Genetic Diseases, Inborn / mortality
  • Genetic Diseases, Inborn / therapy
  • Hematologic Diseases / immunology
  • Hematologic Diseases / mortality
  • Hematologic Diseases / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Infant
  • Length of Stay
  • Lymphopenia / immunology
  • Lymphopenia / mortality*
  • Male
  • Retrospective Studies
  • Risk Factors