Viral reactivations following hematopoietic stem cell transplantation in pediatric patients – A single center 11-year analysis

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.

Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis

“…In two studies, aGvHD was dichotomized in grade ≥3 versus <3; one of them (Juvonen et al [ 66 ]) showed that patients with aGvHD grade ≥3 had a higher risk of active EBV infection (HR = 1.70 (95% CI: 1.11–2.62)). However, this result was not corroborated by other studies [ 51 , 91 , 101 ]. Among eight studies [ 4 , 39 , 41 , 57 , 59 , 74 , 86 , 89 ] that compared grade ≥2 versus <2, two [ 59 , 89 ] showed that an aGvHD grade ≥2 significantly increased the risk of active EBV infection, one reported a positive association without reporting the relative risk (Hiwarkar et al [ 58 ]), and the other (Sirvent-Von Bueltzingsloewen et al [ 89 ]) reported an OR = 3.4 (95% CI: 1.2–9.7).…”

“…In total, 3362 titles were identified in the research bases, 1883 in EMBASE and 1479 in Medline. Once duplicates and papers with exclusion criteria were removed, 77 articles [ 4 , 16 , 23 , 24 , 27 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ,…”

“…The association between acute (a)GvHD and post-transplant EBV infection was examined in 21 studies [ 4 , 39 , 41 , 46 , 51 , 52 , 56 , 57 , 59 , 65 , 66 , 68 , 74 , 76 , 81 , 85 , 86 , 88 , 89 , 91 , 101 ]. Six statistically significant associations were highlighted using different grade categorization of the outcome.…”

Umbilical Cord Blood Transplants: Current Status and Evolving Therapies

“…Cytomegalovirus, Epstein–Barr virus, and adenovirus constitute the majority of significant viremias after HCT. Transplant-related variables that contribute to the risk include the underlying disease, donor and graft source, preparative regimen, and the degree of T cell depletion ( in vivo or ex vivo ) ( 85 , 86 ). Current pharmacologic antiviral prophylaxis and treatment are limited in efficacy and are toxic to various organs ( 87 , 88 ).…”

Az allogén vérképző őssejtátültetés korai szövődményei gyermekkorban

“…A szekunder immundefi ciencia és az immunszuppreszszió miatt a beavatkozás egyik leggyakoribb szövődménye a vírusreaktiváció [5]. Az akut graft -versus-host betegség (GVHD) gyakoriságát és súlyosságát többek közt a transzplantáció és a graft típusa befolyásolja [6].…”