David Deambrosis1, Emma Davies2, Andrew Turner3, Malcolm Guiver3, Denise Bonney1, Helen Campbell1, Robert F Wynn1, Prashant Hiwarkar1. 1. Department of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Oxford Road, Manchester, M13 9WL, United Kingdom. 2. Department of Virology, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, United Kingdom. Electronic address: Emma.davies@mft.nhs.uk. 3. Department of Virology, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, United Kingdom.
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.
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.
Authors: Jeremy D Rubinstein; Xiang Zhu; Thomas Leemhuis; Giang Pham; Lorraine Ray; Sana Emberesh; Sonata Jodele; Shawn Thomas; Jose A Cancelas; Catherine M Bollard; Patrick J Hanley; Michael D Keller; Olivia Grimley; Diana Clark; Teri Clark; Cecilia S Lindestam Arlehamn; Alessandro Sette; Stella M Davies; Adam S Nelson; Michael S Grimley; Carolyn Lutzko Journal: Blood Adv Date: 2021-09-14