title: Impact of viral reactivations in the era of pre-emptive antiviral drug therapy following allogeneic haematopoietic SCT in paediatric recipients.
abstract: 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.
authors.affiliation: Molecular Immunology Unit, Institute of Child Health London, UK. p.hiwarkar@ucl.ac.uk
authors.forename: P
authors.initials: P
authors.lastname: Hiwarkar
authors.forename: H B
authors.initials: HB
authors.lastname: Gaspar
authors.forename: K
authors.initials: K
authors.lastname: Gilmour
authors.forename: M
authors.initials: M
authors.lastname: Jagani
authors.forename: R
authors.initials: R
authors.lastname: Chiesa
authors.forename: N
authors.initials: N
authors.lastname: Bennett-Rees
authors.forename: J
authors.initials: J
authors.lastname: Breuer
authors.forename: K
authors.initials: K
authors.lastname: Rao
authors.forename: C
authors.initials: C
authors.lastname: Cale
authors.forename: N
authors.initials: N
authors.lastname: Goulden
authors.forename: G
authors.initials: G
authors.lastname: Davies
authors.forename: P
authors.initials: P
authors.lastname: Amrolia
authors.forename: P
authors.initials: P
authors.lastname: Veys
authors.forename: W
authors.initials: W
authors.lastname: Qasim
mesh_terms: D000293:Adolescent; D064591:Allografts; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004266:DNA Virus Infections / Q000276:immunology / Q000401:mortality*; D004267:DNA Viruses; D005260:Female; D030342:Genetic Diseases, Inborn / Q000276:immunology / Q000401:mortality / Q000628:therapy; D006402:Hematologic Diseases / Q000276:immunology / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007902:Length of Stay; D008231:Lymphopenia / Q000276:immunology / Q000401:mortality*; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors