Abstract

Viral reactivation occurs frequently in the context of immunodeficiency and immunosuppression after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and can cause severe complications. The aim of this single-center retrospective analysis was to characterize viral infections in the first year after HSCT, to investigate risk factors and to study the impact of viral infections on transplantation outcome. This will facilitate the identification of at-risk patients and the development of new preventive strategies. 107 pediatric allo-HSCT from January 2005 through December 2015 were analyzed for infections with Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), adenovirus (ADV), herpes simplex virus (HSV) and varicella zoster virus (VZV). Viral infections were detected after 68.2% of transplantations. The viruses most commonly encountered were HHV-6 (36/107) and EBV (30/107). Severe viral disease was rare (7/107) and none of the patients died as result of viral reactivation. Important risk factors for viral infections were higher age at HSCT, donor type and occurrence of acute graft-versus-host disease (aGvHD). Especially for EBV, transplant from an unrelated donor and in-vivo T-cell depletion (TCD) had a significant effect on infection rates, whereas for CMV the strongest effect was seen by donor and recipient serostatus with recipient seropositivity most predictive for reactivation. The occurrence of severe aGvHD was associated with EBV and ADV infections. For HSV, the recipient serostatus was identified as prognostic factor for HSV infections, while we found higher age at time of HSCT as risk factor for VZV infections. The overall survival of patients with or without viral infections did not differ significantly. Interestingly, when looking at the 85 patients in our cohort who had received an HSCT for a malignant disease, a tendency towards lower relapse rates was seen in patients affected by viral infections (HR 0.51, 95% CI 0.25 – 1.06, p = 0.072). Viral reactivations are common after pediatric allo-HSCT, though severe complications were rare in our collective. Determining risk factors for viral reactivations may help to identify patients in need of intensified monitoring and to individualize preventive strategies.

Highlights

  • Allogeneic hematopoietic stem cell transplantation is an established therapy for a variety of malignancies, congenital and acquired hematological diseases as well as immunodeficiencies

  • Previous reports on risk factors for viral reactivations after HSCT showed variable results, especially for pediatric patients: An age-dependency, for varicella zoster virus (VZV) reactivation in children, was shown by Vermont et al [4], but the literature available is inconclusive for other members of the herpesvirus family

  • Reactivation of viral infections with Epstein-Barr virus (EBV), CMV, human herpesvirus 6 (HHV-6), ADV, herpes simplex virus (HSV) and VZV after HSCT is common, as we could confirm in this single-center retrospective study

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Summary

Introduction

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established therapy for a variety of malignancies, congenital and acquired hematological diseases as well as immunodeficiencies. While hygienic measures and isolation of the patient protect against some pathogens, a special risk originates from viruses that silently persist within the patient or the transplanted cells. Viruses like Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), adenovirus (ADV), herpes simplex virus (HSV) and varicella zoster virus (VZV) can reactivate especially in the context of immunodeficiency and immunosuppression. Previous reports on risk factors for viral reactivations after HSCT showed variable results, especially for pediatric patients: An age-dependency, for VZV reactivation in children, was shown by Vermont et al [4], but the literature available is inconclusive for other members of the herpesvirus family. In patients receiving a human leukocyte antigen (HLA) mismatched or unrelated transplant, viral infection rates tend to be higher than in matched related donors (MRD) [5]. The reduced amount of mature immunocompetent cells has been generally associated with a decreased protection against viral infections, especially in adult patients [6]

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