Progress in Noninvasive Surveillance for Acute Rejection in Pediatric Heart Transplant Recipients: A Real-World Analysis of Donor-Derived Cell-Free DNA-Based Surveillance Protocol

IF 1.9 4区医学 Q2 SURGERY Clinical Transplantation Pub Date : 2024-10-16 DOI:10.1111/ctr.15481

Leor Akabas, Stephen A. Bravo, Yun Zhang, Anna Simonelli, Warren A. Zuckerman, Marc E. Richmond, Irene D. Lytrivi

{"title":"Progress in Noninvasive Surveillance for Acute Rejection in Pediatric Heart Transplant Recipients: A Real-World Analysis of Donor-Derived Cell-Free DNA-Based Surveillance Protocol","authors":"Leor Akabas, Stephen A. Bravo, Yun Zhang, Anna Simonelli, Warren A. Zuckerman, Marc E. Richmond, Irene D. Lytrivi","doi":"10.1111/ctr.15481","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Purpose</h3>\n \n <p>Acute cellular (ACR) and antibody-mediated (AMR) rejection are risk factors for allograft loss in heart transplant (HT) recipients. Endomyocardial biopsy (EMB), although considered the gold standard for rejection surveillance, is invasive and has high interobserver variability. Noninvasive donor-derived cell-free DNA (dd-cfDNA) sampling has a high negative predictive value (NPV) for rejection in adults and is increasingly used in pediatrics. This single center study aimed to test the performance of dd-cfDNA in screening for acute rejection (AR) and donor-specific antibodies (DSAs) in pediatric HT recipients.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Blood samples for dd-cfDNA were obtained per clinical protocol for all eligible HT recipients in our center from July 1, 2022 to December 31, 2023. Primary endpoints were episodes of AR, pathology grading of EMBs temporally related to ddcfDNA sampling (0–150 days), and presence of DSAs.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>There were 471 interpretable samples, in 192 unique patients. Of those, 199 dd-cfDNA tests were paired with EMB ± DSA in 152 patients. Abnormal dd-cfDNA (> 0.2%) was found in 77 samples (median 0.48%, range 0.21%–11%) and led to EMB, where one sample was positive for ACR (grade 2R), 13 for AMR, yielding an NPV of 97% for AMR. After excluding abnormal ddcfDNA testing associated with AR, 65 abnormal dd-cfDNA tests were paired with DSA testing. The NPV of the test for detection of DSAs was 93%.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Implementation of noninvasive rejection surveillance with dd-cfDNA in a pediatric cohort demonstrates high NPV for AR and high DSAs, making it an ideal screening tool for long-term monitoring of allograft health in pediatrics.</p>\n </section>\n </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"38 10","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2024-10-16","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.15481","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

Purpose

Acute cellular (ACR) and antibody-mediated (AMR) rejection are risk factors for allograft loss in heart transplant (HT) recipients. Endomyocardial biopsy (EMB), although considered the gold standard for rejection surveillance, is invasive and has high interobserver variability. Noninvasive donor-derived cell-free DNA (dd-cfDNA) sampling has a high negative predictive value (NPV) for rejection in adults and is increasingly used in pediatrics. This single center study aimed to test the performance of dd-cfDNA in screening for acute rejection (AR) and donor-specific antibodies (DSAs) in pediatric HT recipients.

Methods

Blood samples for dd-cfDNA were obtained per clinical protocol for all eligible HT recipients in our center from July 1, 2022 to December 31, 2023. Primary endpoints were episodes of AR, pathology grading of EMBs temporally related to ddcfDNA sampling (0–150 days), and presence of DSAs.

Results

There were 471 interpretable samples, in 192 unique patients. Of those, 199 dd-cfDNA tests were paired with EMB ± DSA in 152 patients. Abnormal dd-cfDNA (> 0.2%) was found in 77 samples (median 0.48%, range 0.21%–11%) and led to EMB, where one sample was positive for ACR (grade 2R), 13 for AMR, yielding an NPV of 97% for AMR. After excluding abnormal ddcfDNA testing associated with AR, 65 abnormal dd-cfDNA tests were paired with DSA testing. The NPV of the test for detection of DSAs was 93%.

Conclusion

Implementation of noninvasive rejection surveillance with dd-cfDNA in a pediatric cohort demonstrates high NPV for AR and high DSAs, making it an ideal screening tool for long-term monitoring of allograft health in pediatrics.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

无创监测小儿心脏移植受者急性排斥反应的进展：基于无捐献细胞 DNA 的监测方案的真实世界分析

目的急性细胞（ACR）和抗体介导（AMR）排斥反应是心脏移植（HT）受者丧失异体移植物的风险因素。心内膜活检（EMB）虽然被认为是监测排斥反应的黄金标准，但它具有创伤性，而且观察者之间的差异很大。无创供体源性无细胞DNA（dd-cfDNA）采样对成人排斥反应具有较高的阴性预测值（NPV），并越来越多地应用于儿科。这项单中心研究旨在测试 dd-cfDNA 在筛查小儿 HT 受者急性排斥反应（AR）和供体特异性抗体（DSA）方面的性能。方法从 2022 年 7 月 1 日到 2023 年 12 月 31 日，我们中心按照临床协议为所有符合条件的 HT 受者采集了 dd-cfDNA 血液样本。主要终点是AR发作、与ddcfDNA采样时间相关的EMB病理分级（0-150天）以及是否存在DSA。结果 192 名患者共采集了 471 份可解释样本。其中，199 例 dd-cfDNA 检测与 152 例患者的 EMB ± DSA 配对。在 77 份样本中发现了异常 dd-cfDNA（> 0.2%）（中位数为 0.48%，范围为 0.21%-11%），并进行了 EMB 检测，其中一份样本为 ACR 阳性（2R 级），13 份样本为 AMR 阳性，AMR 的 NPV 为 97%。在排除与 AR 相关的异常 ddcfDNA 检测后，65 例异常 dd-cfDNA 检测与 DSA 检测配对。检测 DSA 的 NPV 为 93%。结论利用 dd-cfDNA 在儿科队列中实施无创排斥监测，对 AR 和高 DSA 有很高的 NPV，使其成为长期监测儿科同种异体移植物健康的理想筛查工具。

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分钟内获得全文去求助

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.