Evaluating threshold for donor fraction cell-free DNA using clinically available assay for rejection in pediatric and adult heart transplantation. Pediatr Transplant 2024 May;28(3):e14708
Date
03/30/2024Pubmed ID
38553812Pubmed Central ID
PMC10987078DOI
10.1111/petr.14708Scopus ID
2-s2.0-85189497658 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
BACKGROUND: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection.
METHODS: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance.
RESULTS: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection.
CONCLUSION: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.
Author List
Deshpande SR, Zangwill SD, Richmond ME, Kindel SJ, Schroder JN, Gaglianello N, Bichell DP, Wigger MA, Knecht KR, Thrush PT, Mahle WT, North PE, Simpson PM, Zhang L, Dasgupta M, Tomita-Mitchell A, Mitchell MEAuthors
Nunzio A. Gaglianello MD Associate Professor in the Medicine department at Medical College of WisconsinMichael Edward Mitchell MD Chief, Professor in the Surgery department at Medical College of Wisconsin
Aoy Tomita Mitchell PhD Professor in the Surgery department at Medical College of Wisconsin
Paula E. North PhD, MD Professor in the Pathology and Laboratory Medicine department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultBiomarkers
Cell-Free Nucleic Acids
Child
Graft Rejection
Heart Transplantation
Humans
Prospective Studies
Tissue Donors
