Clinical Utility of Donor‐Derived Cell‐Free DNA in Heart Transplant Recipients With Multi‐Organ Transplants

• Published in: Clinical transplantation Vol. 38; no. 10; pp. e15479 - n/a
• Main Authors: Moeller, Cathrine M., Oren, Daniel, Fernandez Valledor, Andrea, Rubinstein, Gal, Lotan, Dor, Mehlman, Yonatan, Slomovich, Sharon, Rahman, Salwa, Lee, Changhee, Baranowska, Julia, Regan, Matthew, Elad, Boaz, DeFilippis, Ersilia M., Hennecken, Carolyn, Salazar, Ruben, Raikhelkar, Jayant, Clerkin, Kevin J., Fried, Justin, Lin, Edward, Bae, David, Oh, Kyung T., Latif, Farhana, Topkara, Veli K., Naka, Yoshifumi, Takeda, Koji, Majure, David, Uriel, Nir, Sayer, Gabriel
• Format: Journal Article
• Language: English
• Published: Denmark 01-10-2024
• Subjects: Adult; Biomarkers - blood; Cell-Free Nucleic Acids - blood; donor‐derived cell‐free DNA; Female; Follow-Up Studies; Graft Rejection - blood; Graft Rejection - diagnosis; Graft Rejection - etiology; Graft Survival; Heart Transplantation - adverse effects; Humans; Male; Middle Aged; multi‐organ transplantation; Organ Transplantation - adverse effects; Prognosis; rejection; Retrospective Studies; Risk Factors; Tissue Donors; Transplant Recipients; donor‐derived cell‐free DNA; multi‐organ transplantation; rejection
• ISSN: 0902-0063; 1399-0012; 1399-0012
• DOI: 10.1111/ctr.15479

ABSTRACT
Background
Donor‐derived cell‐free DNA (dd‐cfDNA) has emerged as a reliable, noninvasive method for the surveillance of allograft rejection in heart transplantation (HT) patients, but its utility in multi‐organ transplants (MOT) is unknown. We describe our experience using dd‐cfDNA in simultaneous MOT recipients.
Methods
A single‐center retrospective review of all HT recipients between 2018 and 2022 that had at least one measurement of dd‐cfDNA collected. Patients who had simultaneous MOT were identified and included in this study. Levels of dd‐cfDNA were paired with endomyocardial biopsies (EMB) performed within 1 month of blood testing if available. Acute cellular rejection (ACR) was defined as ISHLT (International Society for Heart and Lung Transplantation) grade ≥ 2R. and antibody‐mediated rejection (AMR) was defined as pAMR grade > 0. The within‐patient variability score of the dd‐cfDNA was calculated by the variance/average.
Results
The study included 25 multiorgan transplant recipients: 13 heart–kidney (H‐K), 8 heart–liver (H‐Li), and 4 heart–lung (H‐Lu). The median age was 55 years, 44% were female; the median time from HT until the first dd‐cfDNA measurement was 4.5 months (IQR 2, 10.5). The median dd‐cfDNA level was 0.18% (IQR 0.15%, 0.27%) for H‐K, 1.15% (IQR 0.77%, 2.33%) for H‐Li, and 0.69% (IQR 0.62%, 1.07%) for H‐Lu patients (p < 0.001). Prevalence of positive dd‐cfDNA tests (threshold of 0.20%) were 42.2%, 97.3%, and 92.3% in the H‐K, H‐Li, and H‐Lu groups, respectively. The within‐patient variability score was highest in the H‐Li group (median of 0.45 [IQR 0.29, 0.94]) and lowest in the H‐K group (median of 0.09 [IQR 0.06, 0.12]); p = 0.002. No evidence of cardiac ACR or AMR was found. Three patients experienced renal allograft ACR and/or AMR, two patients experienced rejection of the liver allograft, and one patient experienced an episode of AMR‐mediated lung rejection. One person in the H‐K group experienced an episode of cardiac allograft dysfunction that was not associated with biopsy‐confirmed rejection.
Conclusion
Dd‐cfDNA is chronically elevated in most MOT recipients. There is a high degree of within‐patient variability in levels (particularly for H‐Li and H‐Lu recipients), which may limit the utility of this assay in monitoring MOT recipients.