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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/221585
Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR)
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BACKGROUND: There is a long-standing need for a noninvasive biomarker that allows monitoring of cardiac allograft rejection, avoiding the need for periodic endomyocardial biopsies (EMB). METHODS: Multicenter, observational, prospective study, performed between 2019 and 2023 (NCT 04973943). All patients underwent 7 per-protocol surveillance EMB during the first postheart transplantation year. Donor-derived cell-free DNA (dd-cfDNA) levels were determined before each EMB, using Next Generation Sequencing Technology (Allonext assay, Eurofins Genome). The primary end-point was the association between dd-cfDNA levels and the presence of acute cellular rejection (ACR) in EMB. RESULTS: The study included 206 patients from 12 centers, with 1,090 pairs of EMB/dd-cfDNA determinations available for analysis. EMB with ACR (n = 49) were associated with dd-cfDNA levels significantly higher than those without, median 0.189% (interquartilic range 0.05-0.70) vs 0.095% (0.04-0.23), p = 0.013. A dd-cfDNA threshold of 0.10% showed a negative predictive value for ACR of 97%. A statistically significant association between N-terminal prohormone of brain (NTProBNP) and dd-cfDNA was also found, with an increase of 0.007% dd-cfDNA (95% confidence interval 0.003-0.011) for every 500 units of NTproBNP, p 0.001. The combination of both biomarkers for diagnosis of ACR showed an area under the receiver operating characteristic (ROC) curve of 0.681, and this combined approach was significantly better than dd-cfDNA alone (area under the ROC curve 0.603), p = 0.016. Using a cut-off point of 0.10% for dd-cfDNA and 1,000 UI/ml for NTproBNP, negative predictive value increased to 98.1%. CONCLUSIONS: dd-cfDNA may be a useful biomarker to rule out significant ACR in a low-risk population. However, a dd-cfDNA value above normal threshold does not correlate robustly with the presence of disease. The combination with NTproBNP, a readily available biomarker, increased the discrimination power of dd-cfDNA alone. CLINICAL TRIAL NOTATION: Donor-derived Cell-Free DNA as a New Biomarker in Cardiac Acute Rejection, NCT 04973943. J Heart Lung Transplant 2025;44:560-569 (c) 2024 The Authors. Published by Elsevier Inc. on behalf of International Society for Heart and Lung Transplantation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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JIMÉNEZ BLANCO, Marta, CRESPO LEIRO, María g., GARCÍA COSÍO, María dolores, GÓMEZ BUENO, Manuel, LÓPEZ VILELLA, Raquel, ORTIZ BAUTISTA, Carlos, FARRERO, Marta, ZEGRÍ REIRIZ, Isabel, DÍAZ MOLINA, Beatriz, GARCÍA ROMERO, Elena, RANGEL SOUSA, Diego, SALTERAIN, Nahikari, GARRIDO BRAVO, Iris, SEGOVIA CUBERO, Javier. Donor-derived cell-free DNA as a new biomarker for cardiac allograft rejection: A prospective study (FreeDNA-CAR). _The Journal of Heart and Lung Transplantation_. 2024. Vol. 44, núm. 4, pàgs. 560-569. [consulta: 29 de gener de 2026]. ISSN: 1557-3117. [Disponible a: https://hdl.handle.net/2445/221585]