Early findings after integration of donor‐derived cell‐free DNA into clinical care following pediatric heart transplantation

Background Endomyocardial biopsy (EMB) is costly and discomforting yet remains a key component of surveillance after pediatric heart transplantation (HT). Donor‐derived cell‐free DNA (dd‐cfDNA) has been histologically validated with high negative predictive value, offering an alternative to surveill...

Full description

Saved in:
Bibliographic Details
Published in:Pediatric transplantation 2022-02, Vol.26 (1), p.e14124-n/a
Main Authors: Feingold, Brian, Rose‐Felker, Kirsten, West, Shawn C., Zinn, Matthew D., Berman, Pamela, Moninger, Allison, Huston, Allison, Stinner, Brenda, Xu, Qingyong, Zeevi, Adriana, Miller, Susan A.
Format: Article
Language:English
Subjects:
Adolescent
Biomarkers - blood
Biopsy
Cell-Free Nucleic Acids - blood
cell‐free DNA
Child
Child, Preschool
Deoxyribonucleic acid
DNA
endomyocardial biopsy
Female
Follow-Up Studies
Graft rejection
Graft Rejection - blood
Graft Rejection - diagnosis
Graft Rejection - pathology
Heart Transplantation
Humans
Immunosuppression
Infant
Male
Myocardium - pathology
pediatric
Pediatrics
Posttransplant lymphoproliferative disorders
rejection surveillance
Surveillance
Tissue Donors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background Endomyocardial biopsy (EMB) is costly and discomforting yet remains a key component of surveillance after pediatric heart transplantation (HT). Donor‐derived cell‐free DNA (dd‐cfDNA) has been histologically validated with high negative predictive value, offering an alternative to surveillance EMB (sEMB). Methods We implemented an alternative surveillance protocol using commercially available dd‐cfDNA assays in place of sEMB after pediatric HT. Recipients ≧7 months post‐HT with reassuring clinical assessment were referred for dd‐cfDNA. When not elevated above the manufacturers' threshold, sEMB was deferred. Subsequent clinical status and results of follow‐up EMB were analyzed. Results Over 17 months, 58 recipients [34% female, median age at HT 3.1 years (IQR 0.6–10.6)] had dd‐cfDNA assessed per protocol. Median age was 14.8 years (8.4–18.3) and time from HT 6.0 years (2.2–11.2). Forty‐seven (81%) had non‐elevated dd‐cfDNA and 11 (19%) were elevated. During a median of 8.7 months (4.2–15), all are alive without allograft loss/new dysfunction. Among those with non‐elevated dd‐cfDNA, 24 (51%) had subsequent sEMB at 12.1 months (6.9–12.9) with 23 showing no acute rejection (AR): grade 0R/pAMR0 (n = 16); 1R(1A)/pAMR0 (n = 7). One had AR (grade 2R(3A)/pAMR0) on follow‐up sEMB after decreased immunosuppression following a diagnosis of PTLD. All 11 with elevated dd‐cfDNA had reflex EMB at 19 days (12–32) with AR in 4: grade 1R(1B‐2)/pAMR0 (n = 3); 1R(1B)/pAMR2 (n = 1). Conclusions dd‐cfDNA assessment in place of selected, per‐protocol EMB decreased surveillance EMB by 81% in our pediatric HT recipient cohort with no short‐term adverse outcomes. Individual center approach to surveillance EMB will influence the utility of these findings.
ISSN:1397-3142
1399-3046
DOI:10.1111/petr.14124