Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb;26(1):e14124.
doi: 10.1111/petr.14124. Epub 2021 Aug 22.

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

Brian Feingold  1   2   3 , Kirsten Rose-Felker  1   3 , Shawn C West  1   3 , Matthew D Zinn  1   3 , Pamela Berman  3 , Allison Moninger  3 , Allison Huston  3 , Brenda Stinner  3 , Qingyong Xu  4 , Adriana Zeevi  4 , Susan A Miller  1   3
Affiliations

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

Brian Feingold et al. Pediatr Transplant. 2022 Feb.

Abstract

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.

Keywords: cell-free DNA; endomyocardial biopsy; heart transplantation; pediatric; rejection surveillance.

PubMed Disclaimer

References

REFERENCES

    1. Godown J, Harris MT, Burger J, Dodd DA. Variation in the use of surveillance endomyocardial biopsy among pediatric heart transplant centers over time. Pediatr Transplant. 2015;19(6):612-617. 10.1111/petr.12518
    1. Zinn MD, Wallendorf MJ, Simpson KE, Osborne AD, Kirklin JK, Canter CE. Impact of routine surveillance biopsy intensity on the diagnosis of moderate to severe cellular rejection and survival after pediatric heart transplantation. Pediatr Transplant. 2018;22(3):e13131. 10.1111/petr.13131
    1. O'Byrne ML, Glatz AC, Faerber JA, et al. Interhospital variation in the costs of pediatric/congenital cardiac catheterization laboratory procedures: analysis of data from the pediatric health information systems database. J Am Heart Assoc. 2019;8(9):e011543.
    1. Daly KP, Marshall AC, Vincent JA, et al. Endomyocardial biopsy and selective coronary angiography are low-risk procedures in pediatric heart transplant recipients: results of a multicenter experience. J Heart Lung Transplant. 2012;31(4):398-409.
    1. Green A, McSweeney J, Ainley K, Bryant J. In my shoes: children's quality of life after heart transplantation. Prog Transplant. 2007;17(3):199-207; quiz 208.