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用于预测亲缘单倍体造血干细胞移植中供者特异性抗 HLA 抗体脱敏的简易预测因子。

A simple predictor for donor-specific anti-HLA antibody desensitisation in haploidentical haematopoietic stem cell transplantation.

机构信息

Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Transfusion Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

HLA. 2024 Aug;104(2):e15625. doi: 10.1111/tan.15625.

Abstract

Donor-specific HLA antibody (DSA) has been recognised as an independent risk factor for graft failure in patients undergoing haploidentical haematopoietic stem cell transplantation (HID HSCT). Therapeutic plasma exchange (TPE), as a first-line strategy for DSA desensitisation, can promptly reduce serum DSA levels. This study aimed to investigate DSA characteristics and identify a biomarker predicting the efficacy of DSA desensitisation in patients proceeding to HID HSCT. We retrospectively enrolled 32 patients with DSA from April 2021 to January 2024, and analysed the mean fluorescence intensity (MFI) value of DSA at the different time points of desensitisation treatment. Compared with baseline DSA level before TPE, the median MFI of HLA class I DSA was reduced from 8178.6 to 795.3 (p < 0.001), and HLA class II DSA decreased from 6210.9 to 808.8 (p < 0.001) after TPE. The DSA level in 1:16 diluted pre-TPE serum correlated well with DSA value in post-TPE serum (class I, r = 0.85, p < 0.0001; class II, r = 0.94, p < 0.0001), predicting TPE efficacy in 84.4% of patients. Based on the degree of DSA reduction after TPE, patients were divided into complete responders (decreased by >70%), partial responders (decreased by 30 to 70%) and non-responders (decreased by <30%) and the percentages were 43.8%, 25% and 31.2%, respectively. Non-responders receiving aggressive immunotherapy had longer overall survival compared to those receiving standard strategies (p < 0.05). The 1:16 diluted pre-TPE serum may predict the efficacy of TPE and allow for more rational immunotherapy strategy for patients with DSA proceeding to HID HSCT.

摘要

供者特异性 HLA 抗体(DSA)已被认为是接受单倍体造血干细胞移植(HID HSCT)的患者移植物失功的独立危险因素。作为 DSA 脱敏的一线策略,治疗性血浆置换(TPE)可迅速降低血清 DSA 水平。本研究旨在探讨 DSA 的特征,并确定预测接受 HID HSCT 的患者 DSA 脱敏疗效的生物标志物。我们回顾性纳入了 2021 年 4 月至 2024 年 1 月期间 32 例 DSA 患者,并分析了脱敏治疗不同时间点 DSA 的平均荧光强度(MFI)值。与 TPE 前 DSA 基线水平相比,HLA Ⅰ类 DSA 的中位数 MFI 从 8178.6 降至 795.3(p<0.001),HLA Ⅱ类 DSA 从 6210.9 降至 808.8(p<0.001)。TPE 前 1:16 稀释预 TPE 血清中的 DSA 水平与 TPE 后血清中的 DSA 值密切相关(Ⅰ类,r=0.85,p<0.0001;Ⅱ类,r=0.94,p<0.0001),预测 84.4%患者的 TPE 疗效。根据 TPE 后 DSA 降低程度,患者分为完全缓解者(降低>70%)、部分缓解者(降低 30%至 70%)和无反应者(降低<30%),比例分别为 43.8%、25%和 31.2%。接受强化免疫治疗的无反应者的总生存时间长于接受标准策略的无反应者(p<0.05)。1:16 稀释预 TPE 血清可能预测 TPE 的疗效,并为接受 HID HSCT 的 DSA 患者提供更合理的免疫治疗策略。

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