Brian T Fisher1,2,3,4, Craig L K Boge1,2, Hans Petersen5, Alix E Seif6,4, Matthew Bryan2,3,4, Richard L Hodinka7, Ana Maria Cardenas8,9, Dale R Purdy2, Brandon Loudon6, Adriana E Kajon5. 1. Division of Infectious Diseases, Pennsylvania. 2. Center for Pediatric Clinical Effectiveness, Pennsylvania. 3. Division of Oncology, Pennsylvania. 4. Infectious Disease Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico. 5. Infectious Disease Diagnostics Laboratory, Children's Hospital of Philadelphia, Pennsylvania. 6. Department of Pediatrics, Philadelphia. 7. Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. 8. Center for Clinical Epidemiology and Biostatistics, Philadelphia. 9. Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville Health System.
Abstract
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: 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: 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: 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.
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: 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: 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: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.
Authors: Craig L K Boge; Brian T Fisher; Hans Petersen; Alix E Seif; Dale R Purdy; Despoina M Galetaki; Richard L Hodinka; Ana María Cárdenas; Adriana E Kajon Journal: Pediatr Transplant Date: 2019-06-18
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
Authors: Alicia M Alcamo; Michael S Wolf; Lauren J Alessi; Hey J Chong; Michael Green; John V Williams; Dennis W Simon Journal: Pediatrics Date: 2019-12-11 Impact factor: 7.124