Association between adenovirus infection and mortality outcome among pediatric patients after hematopoietic stem cell transplant

Abstract

Background Adenovirus can cause severe diseases in post‐hematopoietic stem cell transplant (HSCT) patients. Because these patients also have many other factors contributing to mortality, it remains controversial whether adenovirus infection itself contributes to increased mortality in these patients. Objective To determine if adenovirus infection contributes to mortality in pediatric post‐HSCT patients. Methods This retrospective cohort study was performed in post HSCT patients, aged 0–18 years old, admitted at Ramathibodi Hospital from 2016 to 2020. Adenovirus infection was defined as the detection of adenovirus in blood or urine by polymerase chain reaction. Multivariate cox regression was used to identify factors associated with death. Results The incidence of overall adenovirus infection (viremia or viruria) in this cohort was 20.8% (26 out of 125 enrolled patients). From the multivariate cox regression analysis, overall adenovirus infection was not significantly associated with death (hazard ratio [HR]: 2.41; 95% confidence interval [CI]: 0.96–6.06; p = .060). However, presence of viremia (HR: 3.90; 95% CI: 1.40–10.86; p = .009), having maximal serum viral load > 10 000 copies/ml (HR: 3.70; 95% CI: 1.20–11.38; p = .023), presence of end‐organ diseases (HR: 3.44; 95% CI: 1.18–10.01; p = .023) were associated with mortality. Underlying diseases requiring long‐term immunosuppressive drugs before HSCT, invasive fungal disease, invasive bacterial infection, cytomegalovirus infection, and longer engraftment time were also associated with mortality. Conclusion Overall adenovirus infection does not appear to play a significant role in mortality in pediatric post‐HSCT patients. However, more invasive forms of adenovirus infection were associated with mortality in these patients.

Adenovirus disease after hematopoietic cell transplantation: A Japanese transplant registry analysis

“…We identified six risk factors associated with mortality in patients with AdV disease after allogeneic HCT. Among them, viremia or disseminated disease, older patient age, and diagnosis within 100 days after HCT were consistently reported in previous studies 10,28,32 . Intermediate, high, or very high rDRI, HCT‐CI ≥3, and previous HCT have not previously been reported.…”

“…Among them, viremia or disseminated disease, older patient age, and diagnosis within 100 days after HCT were consistently reported in previous studies. 10,28,32 Intermediate, high, or very high rDRI, HCT-CI ≥3, and previous HCT have not previously been reported. Our results showed that regardless of the infection burden, AdV disease was associated with an increased risk of mortality after both autologous and allogeneic HCT.…”

Adenovirus infection in allogeneic hematopoietic cell transplantation

“…30 In another study on 125 HCT pediatric patients, the presence of AdV viremia, AdV viral load ≥ 10 4 copies/mL, and endorgan diseases were associated with mortality. 31 Duration and entity of AdV replication have an impact on the patient outcome. In a retrospective analysis of 241 pediatric HCT patients with AdV infection, both a higher peak level and duration of AdV viremia ≥ 10 3 copies/mL were independent risk factors for the 6-month probability of mortality.…”

“…In a prospective study of 238 pediatric HCT, an AdV viral load ≥ 10 4 copies/mL in the blood resulted in an independent risk factor for poor survival 30 . In another study on 125 HCT pediatric patients, the presence of AdV viremia, AdV viral load ≥ 10 4 copies/mL, and end‐organ diseases were associated with mortality 31 . Duration and entity of AdV replication have an impact on the patient outcome.…”

Adenovirus infection in adult patients undergoing allogeneic hematopoietic stem cell transplant: Incidence, clinical management, and outcome

“…However, the impact of viral infectious complications on outcome is recognized to be as significant in adults as in pediatric allo-HSCT recipients. 5 In fact, in the case of ADV viremia (ADVv), the reported mortality rate was up to 73% in adults 6 and 82% in children, [7][8][9] and in more recent series 30% 10 and 25%, [11][12][13][14] respectively.…”