Transplant International (Oct 2023)

Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study

  • Jens Böhmer,
  • Jens Böhmer,
  • Carina Wasslavik,
  • Daniel Andersson,
  • Anders Ståhlberg,
  • Anders Ståhlberg,
  • Anders Ståhlberg,
  • Marianne Jonsson,
  • Håkan Wåhlander,
  • Håkan Wåhlander,
  • Kristjan Karason,
  • Jan Sunnegårdh,
  • Jan Sunnegårdh,
  • Staffan Nilsson,
  • Julia Asp,
  • Julia Asp,
  • Göran Dellgren,
  • Göran Dellgren,
  • Anne Ricksten,
  • Anne Ricksten

DOI
https://doi.org/10.3389/ti.2023.11260
Journal volume & issue
Vol. 36

Abstract

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In this prospective study we investigated a cohort after heart transplantation with a novel PCR-based approach with focus on treated rejection. Blood samples were collected coincidentally to biopsies, and both absolute levels of dd-cfDNA and donor fraction were reported using digital PCR. 52 patients (11 children and 41 adults) were enrolled (NCT03477383, clinicaltrials.gov), and 557 plasma samples were analyzed. 13 treated rejection episodes >14 days after transplantation were observed in 7 patients. Donor fraction showed a median of 0.08% in the cohort and was significantly elevated during rejection (median 0.19%, p < 0.0001), using a cut-off of 0.1%, the sensitivity/specificity were 92%/56% (AUC ROC-curve: 0.78). Absolute levels of dd-cfDNA showed a median of 8.8 copies/mL and were significantly elevated during rejection (median 23, p = 0.0001). Using a cut-off of 7.5 copies/mL, the sensitivity/specificity were 92%/43% for donor fraction (AUC ROC-curve: 0.75). The results support the feasibility of this approach in analyzing dd-cfDNA after heart transplantation. The obtained values are well aligned with results from other trials. The possibility to quantify absolute levels adds important value to the differentiation between ongoing graft damage and quiescent situations.

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