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. 2024 Oct;38(10):e15479.
doi: 10.1111/ctr.15479.

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

Cathrine M Moeller  1 , Daniel Oren  1 , Andrea Fernandez Valledor  1 , Gal Rubinstein  1 , Dor Lotan  1 , Yonatan Mehlman  1 , Sharon Slomovich  1 , Salwa Rahman  1 , Changhee Lee  1 , Julia Baranowska  1 , Matthew Regan  1 , Boaz Elad  1 , Ersilia M DeFilippis  1 , Carolyn Hennecken  1 , Ruben Salazar  1 , Jayant Raikhelkar  1 , Kevin J Clerkin  1 , Justin Fried  1 , Edward Lin  1 , David Bae  1 , Kyung T Oh  1 , Farhana Latif  1 , Veli K Topkara  1 , Yoshifumi Naka  2 , Koji Takeda  2 , David Majure  3 , Nir Uriel  1 , Gabriel Sayer  1
Affiliations

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

Cathrine M Moeller et al. Clin Transplant. 2024 Oct.

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.

Keywords: donor‐derived cell‐free DNA; multi‐organ transplantation; rejection.

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References

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