Contents lists available at ScienceDirect Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv Short communication Burden of adenoviraemia predicts survival in paediatric recipients of allogeneic haematopoietic stem cell transplant David Deambrosis a,1 , Emma Davies b,1, *, Andrew Turner b , Malcolm Guiver b , Denise Bonney a , Helen Campbell a , Robert F. Wynn a , Prashant Hiwarkar a a Department of Blood and Marrow Transplant, Royal Manchester Children’s Hospital, Oxford Road, Manchester, M13 9WL, United Kingdom b Department of Virology, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, United Kingdom ARTICLE INFO Keywords: Adenovirus Viral burden Transplant AUC Non-relapse mortality ABSTRACT Background: Adenoviraemia occurs in 15 to 30% of paediatric allogeneic haematopoietic stem cell transplant (HSCT) recipients, and is a significant cause of morbidity and mortality which lacks satisfactory therapeutic options. The relationship between burden of adenovirus and mortality is poorly defined in this patient group. Objectives: To determine the relationship between adenoviraemia and mortality in paediatric HSCT recipients. Study Design: A retrospective review of blood adenovirus PCR results in paediatric HSCT recipients spanning February 2003 to September 2016 was conducted. Three measures of adenovirus burden were defined; number of days with significant viraemia, peak adenovirus load and Area under the Curve and related to outcome post- HSCT. Results: A total of 62 patients with episodes of positive blood adenovirus PCR were identified for analysis. Adenoviraemia of more than 7 days, peak viral load of > 8000 copies/ml and higher 16 week Area under the Curve were all significantly associated with higher non-relapse mortality in paediatric HSCT recipients. Conclusions: This retrospective analysis highlights the important predictive value of adenoviral load for non- relapse mortality in young allogeneic HSCT recipients. These data also suggest a possible role for use of these measures as end points in trials of novel adenoviral therapies. 1. Background Adenovirus (AdV) infection is a well-recognised cause of mortality following allogeneic Haematopoietic Stem Cell Transplant (HSCT) [1–3]. Recently, cumulative viral burden of double-stranded DNA (dsDNA) viruses has been identified as a potentially important predictor of mortality in adult recipients of HSCT [4,5]. AdV is a dsDNA virus that reactivates in children with increased frequency, occurring in 15–30% of paediatric HSCT recipients compared with less than 10% of adult HSCT recipients [6,7]. The exact relationship between burden of AdV and survival in paediatric HSCT recipients is not well defined so we retrospectively compared this relationship using three separate mea- sures of viral burden. These measures may provide useful efficacy endpoints for clinical trials of anti-AdV therapies. 2. Objectives To determine the relationship between adenoviraemia and mortality in paediatric HSCT recipients using three separate measures of adenovirus burden. 3. Study design A retrospective, non-interventional cohort study of paediatric allo- geneic HSCT recipients who experienced episodes of adenoviraemia following HSCT at the Royal Manchester Children’s Hospital between 01 February 2003 and 01 September 2016 was conducted. At this center, all allogeneic transplant recipients are screened for adenovir- aemia by blood PCR at day 0 then weekly as per local guidelines and more recently in accordance with European Conference on Infections in Leukaemia ECIL-4 guidelines. The AdV PCR is an in-house real time PCR assay using two unique primer sets targeting the hexon gene with an analytical range of 500 to 1 × 10 8 copies/ml as previously described [8]. A detailed chart review of screening results was conducted to identify cases of adenoviraemia, defined as two consecutive positive tests or a single PCR positive > 1000 copies/ml. Data were collected https://doi.org/10.1016/j.jcv.2020.104373 Received 23 December 2019; Received in revised form 10 April 2020; Accepted 14 April 2020 ⁎ Corresponding author at: Department of Clinical Virology, Manchester University NHS Foundation Trust, M13 9WL, United Kingdom. E-mail address: Emma.davies@mft.nhs.uk (E. Davies). 1 Indicates equal contribution to this submitted manuscript. Journal of Clinical Virology 127 (2020) 104373 1386-6532/ © 2020 Elsevier B.V. All rights reserved. T