存在供体特异性抗体时肺移植后的长期无慢性肺移植功能障碍生存
Long-Term Chronic Lung Allograft Dysfunction-Free Survival Following Lung Transplant in the Presence of Donor-Specific Antibodies.
作者信息
Grobman Benjamin, Courtwright Andrew M, Yeung Melissa, Jacob Selvin, Lee Stefi, Sheikh Adil, Keshk Mohamed, Hackman Amy, Coppolino Anthony, Dunning John, Sharma Nirmal, Goldberg Hilary J
机构信息
Harvard Medical School, Boston, Massachusetts, USA.
Division of Pulmonary and Critical Care Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
出版信息
Clin Transplant. 2025 Aug;39(8):e70241. doi: 10.1111/ctr.70241.
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.
背景
患有晚期肺部疾病的高敏患者，其中黑人及西班牙裔女性更为常见，其在等待名单上死亡的风险增加。2012年，我们实施了一项方案，即只要前瞻性补体依赖细胞毒性（CDC）交叉配型为阴性，就接受任何移植前供体特异性抗体（DSA）。我们报告长期结果，包括总生存期和无慢性肺移植功能障碍（CLAD）生存期。
方法
这是一项单中心回顾性队列研究，研究对象为2012年10月1日至2022年12月31日期间的肺移植受者。我们比较了有和没有预先形成的DSA的受者之间的总体无再次移植生存期和无CLAD生存期。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名受者，中位随访时间为4.3年（四分位间距IQR = 2.1 - 6.9）。33名（7.7%）受者有移植前DSA，历史峰值平均荧光强度（MFI）为4200（IQR = 3000 - 6600，范围2100 - 23000）。每位患者的DSA中位数为1（IQR = 1 - 2，范围1 - 8）。有和没有预先形成的DSA的受者之间调整后的总生存期无差异（风险比HR = 1.39，95%置信区间CI = 0.82 - 2.36，p = 0.22），有和没有预先形成的DSA的受者之间调整后的无CLAD生存期也无差异（HR = 1.07，95% CI = 0.65 - 1.75，p = 0.79）。有预先形成的DSA的受者发生ACR的调整后风险没有增加（HR = 0.71，95% CI = 0.29 - 1.75，p = 0.45），但发生AMR的调整后风险增加（HR = 5.02，95% CI = 2.11 - 11.95，p < 0.001）。
结论
在这个中等规模的队列中，在样本量的限制范围内，接受为有预先形成的DSA但CDC交叉配型为阴性的肺移植候选者提供的供体，与总体或无CLAD生存期较差无关。
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