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

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation Pub Date : 2024-10-18 DOI:10.1111/ctr.15479

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

{"title":"Clinical Utility of Donor-Derived Cell-Free DNA in Heart Transplant Recipients With Multi-Organ Transplants","authors":"Cathrine M. Moeller, Daniel Oren, Andrea Fernandez Valledor, Gal Rubinstein, Dor Lotan, Yonatan Mehlman, Sharon Slomovich, Salwa Rahman, Changhee Lee, Julia Baranowska, Matthew Regan, Boaz Elad, Ersilia M. DeFilippis, Carolyn Hennecken, Ruben Salazar, Jayant Raikhelkar, Kevin J. Clerkin, Justin Fried, Edward Lin, David Bae, Kyung T. Oh, Farhana Latif, Veli K. Topkara, Yoshifumi Naka, Koji Takeda, David Majure, Nir Uriel, Gabriel Sayer","doi":"10.1111/ctr.15479","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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 (<i>p</i> < 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]); <b><i>p</i> = 0.002</b>. 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.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Transplantation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/ctr.15479","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"SURGERY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

多器官心脏移植受者体内无捐献细胞 DNA 的临床实用性

背景供体来源的无细胞 DNA（dd-cfDNA）已成为监测心脏移植（HT）患者异体移植排斥反应的一种可靠、无创的方法，但其在多器官移植（MOT）中的应用尚不清楚。我们介绍了在同时接受 MOT 的患者中使用 dd-cfDNA 的经验。方法对 2018 年至 2022 年间所有 HT 受者进行单中心回顾性审查，至少收集了一次 dd-cfDNA 测量结果。同时进行 MOT 的患者被确定并纳入本研究。dd-cfDNA水平与血液检测后1个月内进行的心内膜活检（EMB）（如果有的话）配对。急性细胞排斥反应（ACR）定义为 ISHLT（国际心肺移植学会）等级≥ 2R，抗体介导的排斥反应（AMR）定义为 pAMR 等级 > 0，dd-cfDNA 的患者内变异性评分按方差/平均值计算。结果研究纳入了 25 例多器官移植受者：13例心肾（H-K）、8例心肝（H-Li）和4例心肺（H-Lu）。中位年龄为 55 岁，44% 为女性；从心脏移植到首次 dd-cfDNA 测量的中位时间为 4.5 个月（IQR 2，10.5）。H-K 患者的 dd-cfDNA 水平中位数为 0.18%（IQR 0.15%，0.27%），H-Li 患者的 dd-cfDNA 水平中位数为 1.15%（IQR 0.77%，2.33%），H-Lu 患者的 dd-cfDNA 水平中位数为 0.69%（IQR 0.62%，1.07%）（p <0.001）。H-K 组、H-Li 组和 H-Lu 组 dd-cfDNA 检测阳性率（阈值为 0.20%）分别为 42.2%、97.3% 和 92.3%。H-Li 组患者内部变异性得分最高（中位数为 0.45 [IQR 0.29, 0.94]），H-K 组最低（中位数为 0.09 [IQR 0.06, 0.12]）；P = 0.002。未发现心脏 ACR 或 AMR 的证据。三名患者出现了肾脏异体移植 ACR 和/或 AMR，两名患者出现了肝脏异体移植排斥反应，一名患者出现了 AMR 介导的肺部排斥反应。H-K 组中有一人出现心脏移植物功能障碍，但与活检证实的排斥反应无关。结论大多数 MOT 受体的 Dd-cfDNA 长期升高。患者体内（尤其是H-Li和H-Lu受者）的Dd-cfDNA水平差异很大，这可能会限制该检测方法在监测MOT受者中的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.