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


Journal

Journal of the Pediatric Infectious Diseases Society
ISSN: 2048-7207
Titre abrégé: J Pediatric Infect Dis Soc
Pays: England
ID NLM: 101586049

Informations de publication

Date de publication:
25 Sep 2019
Historique:
received: 20 02 2018
accepted: 01 06 2018
pubmed: 13 6 2018
medline: 3 3 2020
entrez: 13 6 2018
Statut: ppublish

Résumé

Human adenoviruses (HAdVs) are associated with significant morbidity and death after hematopoietic cell transplantation (HCT). In this study, we sought to determine the incidence of HAdV infection among pediatric HCT recipients in the polymerase chain reaction (PCR) testing era, identify risk factors for viremia among patients undergoing HAdV surveillance, and assess the effectiveness of preemptive cidofovir. A single-center retrospective cohort of patients who underwent a transplant within a 10-year period was assembled. The incidence of and outcomes of patients with HAdV infection and disease were determined by PCR results and chart review. A Cox regression model was used for surveilled allogeneic HCT recipients to identify factors associated with viremia. We also used a discrete-time failure model with inverse probability treatment weights to assess the effectiveness of preemptive cidofovir for infection. Among 572 HCT recipients, 76 (13.3%) had ≥1 sample that was HAdV PCR positive (3.5% of autologous HCT recipients and 19.7% of allogeneic HCT recipients). Among 191 allogeneic HCT recipients under surveillance, 58 (30.4%) had HAdV detected from any source, and 50 (26.2%) specifically had viremia. The mortality rate was higher in allogeneic HCT recipients with HAdV infection versus those without infection (25.9% vs 11.3%; P = .01). Factors associated with infection included an age of 6 to 12 years, an absolute lymphocyte count of <200 cells/μL, recent prednisone exposure, and recent bacteremia. Preemptive cidofovir was not associated with a reduced risk of infection progression (odds ratio, 0.96 [95% confidence interval, 0.30-3.05]). HAdV infection is common and associated with an increased rate of death after allogeneic HCT. Using prediction models that incorporate factors associated with HAdV might help target surveillance. Preemptive cidofovir therapy was not protective in a subset of HAdV-positive patients. Larger observational or randomized investigations are necessary, because the utility of surveillance requires effective preemptive therapies.

Sections du résumé

BACKGROUND BACKGROUND
Human adenoviruses (HAdVs) are associated with significant morbidity and death after hematopoietic cell transplantation (HCT). In this study, we sought to determine the incidence of HAdV infection among pediatric HCT recipients in the polymerase chain reaction (PCR) testing era, identify risk factors for viremia among patients undergoing HAdV surveillance, and assess the effectiveness of preemptive cidofovir.
METHODS METHODS
A single-center retrospective cohort of patients who underwent a transplant within a 10-year period was assembled. The incidence of and outcomes of patients with HAdV infection and disease were determined by PCR results and chart review. A Cox regression model was used for surveilled allogeneic HCT recipients to identify factors associated with viremia. We also used a discrete-time failure model with inverse probability treatment weights to assess the effectiveness of preemptive cidofovir for infection.
RESULTS RESULTS
Among 572 HCT recipients, 76 (13.3%) had ≥1 sample that was HAdV PCR positive (3.5% of autologous HCT recipients and 19.7% of allogeneic HCT recipients). Among 191 allogeneic HCT recipients under surveillance, 58 (30.4%) had HAdV detected from any source, and 50 (26.2%) specifically had viremia. The mortality rate was higher in allogeneic HCT recipients with HAdV infection versus those without infection (25.9% vs 11.3%; P = .01). Factors associated with infection included an age of 6 to 12 years, an absolute lymphocyte count of <200 cells/μL, recent prednisone exposure, and recent bacteremia. Preemptive cidofovir was not associated with a reduced risk of infection progression (odds ratio, 0.96 [95% confidence interval, 0.30-3.05]).
CONCLUSIONS CONCLUSIONS
HAdV infection is common and associated with an increased rate of death after allogeneic HCT. Using prediction models that incorporate factors associated with HAdV might help target surveillance. Preemptive cidofovir therapy was not protective in a subset of HAdV-positive patients. Larger observational or randomized investigations are necessary, because the utility of surveillance requires effective preemptive therapies.

Identifiants

pubmed: 29893957
pii: 5035021
doi: 10.1093/jpids/piy049
doi:

Substances chimiques

DNA, Viral 0
Cidofovir JIL713Q00N

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

317-324

Informations de copyright

© The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Auteurs

Brian T Fisher (BT)

Division of Infectious Diseases, Pennsylvania.
Center for Pediatric Clinical Effectiveness, Pennsylvania.
Division of Oncology, Pennsylvania.
Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico.

Craig L K Boge (CLK)

Division of Infectious Diseases, Pennsylvania.
Center for Pediatric Clinical Effectiveness, Pennsylvania.

Hans Petersen (H)

Infectious Disease Diagnostics Laboratory, Children's Hospital of Philadelphia, Pennsylvania.

Alix E Seif (AE)

Department of Pediatrics, Philadelphia.
Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico.

Matthew Bryan (M)

Center for Pediatric Clinical Effectiveness, Pennsylvania.
Division of Oncology, Pennsylvania.
Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico.

Richard L Hodinka (RL)

Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

Ana Maria Cardenas (AM)

Center for Clinical Epidemiology and Biostatistics, Philadelphia.
Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville Health System.

Dale R Purdy (DR)

Center for Pediatric Clinical Effectiveness, Pennsylvania.

Brandon Loudon (B)

Department of Pediatrics, Philadelphia.

Adriana E Kajon (AE)

Infectious Disease Diagnostics Laboratory, Children's Hospital of Philadelphia, Pennsylvania.

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