{"doi":"10.1111/ctr.15479","title":"Clinical Utility of Donor‐Derived Cell‐Free DNA in Heart Transplant Recipients With Multi‐Organ Transplants","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.","journal":"Clinical Transplantation","year":2024,"id":441333,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1087410,"name":"Daniel Oren","orcid":"0000-0002-2447-3713","position":1,"is_corresponding":false},{"id":1253806,"name":"A. Fernandez Valledor","orcid":"0000-0002-6776-8079","position":2,"is_corresponding":false},{"id":1087405,"name":"Gal Rubinstein","orcid":"0000-0003-1735-983X","position":3,"is_corresponding":false},{"id":1087407,"name":"Dor Lotan","orcid":"0000-0003-3501-6259","position":4,"is_corresponding":false},{"id":1142378,"name":"Yonatan Mehlman","orcid":"0009-0004-8869-3901","position":5,"is_corresponding":false},{"id":1087408,"name":"Sharon Slomovich","orcid":"0000-0002-1123-2400","position":6,"is_corresponding":false},{"id":1095843,"name":"Salwa Rahman","orcid":"0000-0002-2123-3845","position":7,"is_corresponding":false},{"id":727626,"name":"Changhee Lee","orcid":"0000-0003-3194-7240","position":8,"is_corresponding":false},{"id":1254390,"name":"Julia Baranowska","orcid":null,"position":9,"is_corresponding":false},{"id":1254391,"name":"Matthew Regan","orcid":null,"position":10,"is_corresponding":false},{"id":1253807,"name":"B. Elad","orcid":"0000-0001-9253-2351","position":11,"is_corresponding":false},{"id":260663,"name":"Ersilia M. DeFilippis","orcid":"0000-0002-0493-1326","position":12,"is_corresponding":false},{"id":1253808,"name":"C. Hennecken","orcid":"0000-0001-8816-7937","position":13,"is_corresponding":false},{"id":1253809,"name":"Ruben Salazar","orcid":"0000-0002-0639-2602","position":14,"is_corresponding":false},{"id":281839,"name":"J. Raikhelkar","orcid":"0000-0002-8561-7899","position":15,"is_corresponding":false},{"id":281842,"name":"Kevin J. Clerkin","orcid":"0000-0001-8351-9219","position":16,"is_corresponding":false},{"id":1254392,"name":"Justin Fried","orcid":null,"position":17,"is_corresponding":false},{"id":1135827,"name":"Edward Lin","orcid":"0000-0002-2371-8117","position":18,"is_corresponding":false},{"id":1230551,"name":"D. Bae","orcid":"0000-0002-4699-3736","position":19,"is_corresponding":false},{"id":1048264,"name":"Kyung Taek Oh","orcid":"0000-0002-4379-7238","position":20,"is_corresponding":false},{"id":494070,"name":"F. Latif","orcid":"0000-0002-4127-656X","position":21,"is_corresponding":false},{"id":271777,"name":"Veli K. Topkara","orcid":"0000-0002-2236-2008","position":22,"is_corresponding":false},{"id":199064,"name":"Yoshifumi Naka","orcid":null,"position":23,"is_corresponding":false},{"id":264041,"name":"Koji Takeda","orcid":"0000-0001-8263-1911","position":24,"is_corresponding":false},{"id":334555,"name":"David T. Majure","orcid":"0000-0002-8951-0079","position":25,"is_corresponding":false},{"id":104009,"name":"Nir Uriel","orcid":"0000-0003-2301-3587","position":26,"is_corresponding":false},{"id":1253810,"name":"G. Sayer","orcid":"0000-0001-9508-5657","position":27,"is_corresponding":false},{"id":1087406,"name":"C. Moeller","orcid":"0009-0000-6175-2212","position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":null,"created_at":"2026-07-19T02:01:06.281460Z","pmid":"39422086","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}