Faculty Collaboration Database

Donor fraction cell-free DNA and rejection in adult and pediatric heart transplantation. J Heart Lung Transplant 2020 May;39(5):454-463

Date

01/28/2020

Pubmed ID

31983667

DOI

10.1016/j.healun.2019.11.015

Scopus ID

2-s2.0-85078178592 (requires institutional sign-in at Scopus site)   57 Citations

Abstract

BACKGROUND: Endomyocardial biopsy (EMB) is the current standard for rejection surveillance in heart transplant recipients. The quantification of donor-specific cell-free DNA (cfDNA) may be an appropriate biomarker for non-invasive rejection surveillance. A multicenter prospective blinded study (DNA-Based Transplant Rejection Test, DTRT) investigated the value of donor fraction (DF), defined as the ratio of cfDNA specific to the transplanted organ to the total amount of cfDNA present in a blood sample.

METHODS: A total of 241 heart transplant patients were recruited from 7 centers. Age at transplant ranged from 8 days to 73 years, with 146 subjects <18 years and 95 ≥18 years. All the patients were followed for at least 1 year, with blood samples drawn at routine and for-cause biopsies. A total of 624 biopsy-paired samples were included for analysis through a commercially available cfDNA assay (myTAI_HEART, TAI Diagnostics Inc.). A blinded analysis of repeated measures compared the outcomes using receiver operating characteristic (ROC) curves. All primary clinical end-points were monitored at 100%. All analysis and conclusions were reviewed by both an independent external oversight committee and the National Institutes of Health-mandated DTRT steering committee.

RESULTS: DF in acute cellular rejection (ACR) 1R/2R (n = 15) was higher than ACR 0R (n = 42) (p = 0.02); DF in antibody-mediated rejection pAMR1 (n = 8) and pAMR2 (n = 12) (p = 0.05) were higher than pAMR0 (n = 466) (p = 0.04 and p = 0.05 respectively). An optimal DF threshold was determined by the use of an ROC analysis, which ruled out the presence of either ACR or antibody-mediated rejection.

CONCLUSIONS: The cell-free DNA DF holds promise as a non-invasive diagnostic test to rule out acute rejection in both adult and pediatric heart transplant populations.

Author List

Richmond ME, Zangwill SD, Kindel SJ, Deshpande SR, Schroder JN, Bichell DP, Knecht KR, Mahle WT, Wigger MA, Gaglianello NA, Pahl E, Simpson PM, Dasgupta M, North PE, Hidestrand M, Tomita-Mitchell A, Mitchell ME

Authors

Nunzio A. Gaglianello MD Associate Professor in the Medicine department at Medical College of Wisconsin
Steven J. Kindel MD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Michael 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

Adolescent
Adult
Aged
Biomarkers
Biopsy
Cell-Free Nucleic Acids
Child
Child, Preschool
Female
Follow-Up Studies
Graft Rejection
Heart Transplantation
Humans
Infant
Infant, Newborn
Male
Middle Aged
Myocardium
Prognosis
Prospective Studies
ROC Curve
Tissue Donors
Young Adult