Relationship between donor fraction cell-free DNA and clinical rejection in heart transplantation. Pediatr Transplant 2022 Jun;26(4):e14264
Date
03/09/2022Pubmed ID
35258162DOI
10.1111/petr.14264Scopus ID
2-s2.0-85125904987 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
BACKGROUND: Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell-free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest.
METHODS: Patients with heart transplantation were enrolled in two sequential, multi-center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA.
RESULTS: A total of 835 samples from 269 subjects (57% pediatric) were included for this analysis, including 28 samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p < .0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post-therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p < .0001).
CONCLUSION: DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients.
Author List
Deshpande SR, Zangwill SD, Kindel SJ, Schroder JN, Bichell DP, Wigger MA, Richmond ME, Knecht KR, Pahl E, Gaglianello NA, Mahle WT, Stamm KD, Simpson PM, Dasgupta M, Zhang L, North PE, Tomita-Mitchell A, Mitchell MEAuthors
Steven J. Kindel MD Associate Professor in the Pediatrics 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 MD, PhD Professor in the Pathology 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
BiomarkersCell-Free Nucleic Acids
Child
Graft Rejection
Heart Transplantation
Humans
Tissue Donors
