Long-Term Chronic Lung Allograft Dysfunction-Free Survival Following Lung Transplant in the Presence of Donor-Specific Antibodies

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation Pub Date : 2025-07-23 DOI:10.1111/ctr.70241

Benjamin Grobman, Andrew M. Courtwright, Melissa Yeung, Selvin Jacob, Stefi Lee, Adil Sheikh, Mohamed Keshk, Amy Hackman, Anthony Coppolino, John Dunning, Nirmal Sharma, Hilary J. Goldberg

{"title":"Long-Term Chronic Lung Allograft Dysfunction-Free Survival Following Lung Transplant in the Presence of Donor-Specific Antibodies","authors":"Benjamin Grobman, Andrew M. Courtwright, Melissa Yeung, Selvin Jacob, Stefi Lee, Adil Sheikh, Mohamed Keshk, Amy Hackman, Anthony Coppolino, John Dunning, Nirmal Sharma, Hilary J. Goldberg","doi":"10.1111/ctr.70241","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Highly sensitized patients with advanced lung disease, who are more often Black and Hispanic women, are at increased risk for waitlist death. In 2012, we implemented a protocol to cross any pre-transplant donor-specific antibody (DSA), so long as a prospective complement-dependent cytotoxicity (CDC) crossmatch was negative. We report long-term outcomes, including overall survival and chronic lung allograft dysfunction (CLAD)-free survival.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This was a single-institution retrospective cohort study of lung transplant recipients between October 1, 2012–December 31, 2022. We compared overall retransplant-free survival and CLAD-free survival between recipients with and without pre-formed DSA. Secondary outcomes included freedom from acute cellular rejection (ACR) and antibody-mediated rejection (AMR).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The study cohort included 427 recipients with a median duration of follow-up of 4.3 years (IQR = 2.1–6.9). Thirty-three (7.7%) recipients had pre-transplant DSA with a peak historical mean fluorescence intensity (MFI) of 4200 (IQR = 3000–6600, total range 2100–23 000). The median number of DSA per patient was 1 (IQR = 1–2, total range 1–8). There was no difference in adjusted overall survival between recipients with and without pre-formed DSA (HR = 1.39, 95% CI = 0.82–2.36, <i>p</i> = 0.22) or adjusted CLAD-free survival between recipients with and without pre-formed DSA (HR = 1.07, 95% CI = 0.65–1.75, <i>p</i> = 0.79). Recipients with pre-formed DSA did not have increased adjusted hazard of ACR (HR = 0.71, 95% CI = 0.29–1.75, <i>p</i> = 0.45) but did have increased adjusted hazard of AMR (HR = 5.02, 95% CI = 2.11–11.95, <i>p</i> < 0.001).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>In this moderately-sized cohort, a protocol of accepting donor offers for lung transplant candidates with pre-formed DSA but negative CDC crossmatch was not associated with worse overall or CLAD-free survival, within the limitations of the sample size.</p>\n </section>\n </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 8","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-07-23","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.70241","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

Highly sensitized patients with advanced lung disease, who are more often Black and Hispanic women, are at increased risk for waitlist death. In 2012, we implemented a protocol to cross any pre-transplant donor-specific antibody (DSA), so long as a prospective complement-dependent cytotoxicity (CDC) crossmatch was negative. We report long-term outcomes, including overall survival and chronic lung allograft dysfunction (CLAD)-free survival.

Methods

This was a single-institution retrospective cohort study of lung transplant recipients between October 1, 2012–December 31, 2022. We compared overall retransplant-free survival and CLAD-free survival between recipients with and without pre-formed DSA. Secondary outcomes included freedom from acute cellular rejection (ACR) and antibody-mediated rejection (AMR).

Results

The study cohort included 427 recipients with a median duration of follow-up of 4.3 years (IQR = 2.1–6.9). Thirty-three (7.7%) recipients had pre-transplant DSA with a peak historical mean fluorescence intensity (MFI) of 4200 (IQR = 3000–6600, total range 2100–23 000). The median number of DSA per patient was 1 (IQR = 1–2, total range 1–8). There was no difference in adjusted overall survival between recipients with and without pre-formed DSA (HR = 1.39, 95% CI = 0.82–2.36, p = 0.22) or adjusted CLAD-free survival between recipients with and without pre-formed DSA (HR = 1.07, 95% CI = 0.65–1.75, p = 0.79). Recipients with pre-formed DSA did not have increased adjusted hazard of ACR (HR = 0.71, 95% CI = 0.29–1.75, p = 0.45) but did have increased adjusted hazard of AMR (HR = 5.02, 95% CI = 2.11–11.95, p < 0.001).

Conclusions

In this moderately-sized cohort, a protocol of accepting donor offers for lung transplant candidates with pre-formed DSA but negative CDC crossmatch was not associated with worse overall or CLAD-free survival, within the limitations of the sample size.

查看原文本刊更多论文

供体特异性抗体存在下肺移植后长期慢性肺移植无功能障碍存活

背景：高度敏感的晚期肺部疾病患者，多为黑人和西班牙裔女性，在等候名单中死亡的风险增加。2012年，我们实施了一项方案，只要预期补体依赖性细胞毒性（CDC）交叉配型为阴性，就可以交叉任何移植前供体特异性抗体（DSA）。我们报告了长期结果，包括总生存期和无慢性同种异体肺功能障碍（chronic lung allograft dysfunction， CLAD）生存期。方法：2012年10月1日至2022年12月31日，对肺移植受者进行单机构回顾性队列研究。我们比较了有和没有预先形成的DSA的受者的总体无再移植生存率和无clad生存率。次要结局包括无急性细胞排斥反应（ACR）和抗体介导的排斥反应（AMR）。结果研究队列包括427名接受者，中位随访时间为4.3年（IQR = 2.1-6.9）。33例（7.7%）接受移植前DSA，峰值历史平均荧光强度（MFI）为4200 （IQR = 3000-6600，总范围2100 - 23000）。每位患者DSA的中位数为1 （IQR = 1 - 2，总范围1 - 8）。接受和不接受预成型DSA的受者的调整总生存率（HR = 1.39, 95% CI = 0.82-2.36, p = 0.22）和接受和不接受预成型DSA的受者的调整无clad生存率（HR = 1.07, 95% CI = 0.65-1.75, p = 0.79）无差异。预成形DSA受者没有增加ACR的调整风险（HR = 0.71, 95% CI = 0.29-1.75, p = 0.45），但确实增加了AMR的调整风险(HR = 5.02, 95% CI = 2.11-11.95, p <；0.001)。在这个中等规模的队列中，在样本量的限制下，接受预先形成的DSA但CDC交叉匹配阴性的肺移植候选人供体offer的方案与更差的总生存率或无clad生存率无关。

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.