Incidence and Outcomes of Human Adenovirus Infection and Disease in a Multicenter Cohort of Pediatric Allogeneic Hematopoietic Cell Transplant Recipients.

Abstract

Human adenovirus (HAdV) among pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients can result in asymptomatic infection with risk for disease progression. There are limited data defining HAdV infection, disease, and case-fatality rates in a HAdV polymerase chain reaction (PCR) surveillance testing era. The current study aimed to define these outcomes using a priori definitions applied by a central review committee. Pediatric allo-HCT recipients were followed up for 180 days after HCT at 10 pediatric institutions. Blood and stool specimens were collected 0-7 days prior to allo-HCT for serum HAdV immunoglobulin G and stool HAdV PCR testing. Clinical data, including HAdV PCR testing results, informed central review committee-designated outcomes of HAdV infection, including DNAemia, disease, and deaths (case-fatality rate). Outcomes were reported by HAdV surveillance testing status and by pretransplant research specimen results. The cohort included 819 allo-HCT recipients; 649 (79.2%) were under HAdV surveillance. The HAdV infection and DNAemia incidence among surveilled patients was 27.1% and 16.0%, respectively. The incidence of proven or probable HAdV disease was 10.9% for the cohort and, 12.6% for those under surveillance. The HAdV infection incidence was highest (13 of 25 [52.0%]) in patients with pre-HCT HAdV immunoglobulin G and stool PCR positivity. The attributable case-fatality rate for those with proven or probable disease was 13.5%. HAdV infection and disease are common among pediatric allo-HCT recipients. HAdV disease is associated with a substantial HAdV-attributable mortality rate. Clinical trials assessing novel HAdV in pediatric allo-HCT recipients are needed. Pretransplant serology and stool PCR testing could identify high-risk patients for trial enrollment.