Early changes in cell-free DNA levels in newly transplanted heart transplant patients

Pediatr Transplant. 2020 Feb;24(1):e13622. doi: 10.1111/petr.13622. Epub 2019 Dec 11.

Abstract

Heart transplantation is a well-established therapy for end-stage heart failure in children and young adults. The highest risk of graft loss occurs in the first 60 days post-transplant. Donor fraction of cell-free DNA is a highly sensitive marker of graft injury. Changes in cell-free DNA levels have not previously been studied in depth in patients early after heart transplant. A prospective study was conducted among heart transplant recipients at a single pediatric heart center. Blood samples were collected from children and young adult transplant patients at three time points within 10 days of transplantation. DF and total cell-free DNA levels were measured using a targeted method (myTAIHEART ). In 17 patients with serial post-transplant samples, DF peaks in the first 2 days after transplant (3.5%, [1.9-10]%) and then declines toward baseline (0.27%, [0.19-0.52]%) by 6-9 days. There were 4 deaths in the first year among the 10 patients with complete sample sets, and 3 out of 4 who died had a late rise or blunted decline in donor fraction. Patients who died trended toward an elevated total cell-free DNA at 1 week (41.5, [34-65] vs 13.6, [6.2-22] P = .07). Donor fraction peaks early after heart transplant and then declines toward baseline. Patients without sustained decline in donor fraction and/or elevated total cell-free DNA at 1 week may have worse outcomes.

Keywords: biomarkers; cell-free DNA; early postoperative period; pediatric heart transplant.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Cell-Free Nucleic Acids / blood*
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Graft Rejection / blood
  • Graft Rejection / diagnosis*
  • Heart Failure / mortality
  • Heart Failure / surgery*
  • Heart Transplantation* / mortality
  • Humans
  • Infant
  • Male
  • Pilot Projects
  • Postoperative Period
  • Prospective Studies
  • Tissue Donors
  • Young Adult

Substances

  • Biomarkers
  • Cell-Free Nucleic Acids