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高剂量免疫球蛋白干预作为一种有效且简单的策略,用于 HLA 抗体同种异型移植的供体特异性脱敏。

High-Dose immunoglobulin Intervention as an effective and simple strategy for donor specific Anti-HLA antibody desensitization in haploidentical transplant.

机构信息

Department of Hematology, Peking University First Hospital, Beijing, China.

Department of Hematology, Peking University First Hospital, Beijing, China.

出版信息

Int Immunopharmacol. 2023 Jul;120:110299. doi: 10.1016/j.intimp.2023.110299. Epub 2023 May 16.

Abstract

Donor-specific anti-HLA antibody (DSA) is a significant obstacle to successful haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and is associated with poor engraftment rates. DSA strongly positive patients with a mean fluorescence intensity (MFI) over 5000 have a primary poor graft function (PGF) rate of over 60%. Currently, there is no consensus on the desensitization of DSA, and existing strategies are complex and have limited effectiveness. To address this issue, we conducted a retrospective study on 19 patients with strongly positive DSA (MFI over 5000) who underwent haplo-HSCT and were treated with intravenous immunoglobulin (IVIg)-based therapy. We also included 38 baseline-matched patients with DSA-negative as controls. Our findings revealed that the cumulative incidence of engraftment, PGF, graft-versus-host disease (GVHD), virus infection, overall survival (OS), disease-free survival (DFS), relapse, and non-relapse mortality (NRM) in the DSA strongly positive group after desensitization were comparable to those in the DSA negative group (P > 0.05). Our multivariable analysis showed that disease remission was a protective factor against PGF (P = 0.005, OR = 0.019, 95% CI 0.001-0.312). Subgroup analysis revealed that the desensitization efficacy was equal regardless of DSA type against HLA-I or II, and MFI value over 5000 or not. In conclusion, we propose a simple and effective DSA desensitization strategy based on immunoglobulin to ensure successful engraftment and improve patient prognosis.

摘要

供者特异性抗 HLA 抗体(DSA)是影响单倍体造血干细胞移植(haplo-HSCT)成功的重要障碍,与植入率低有关。DSA 强阳性(平均荧光强度(MFI)超过 5000)的患者,原发性植入不良(PGF)率超过 60%。目前,对于 DSA 的脱敏尚无共识,现有的策略复杂且效果有限。为了解决这一问题,我们对 19 例 MFI 超过 5000 的 DSA 强阳性患者进行了回顾性研究,这些患者接受了haplo-HSCT,并接受了基于静脉注射免疫球蛋白(IVIg)的治疗。我们还纳入了 38 例基线匹配的 DSA 阴性患者作为对照。我们的研究结果显示,脱敏后 DSA 强阳性组的植入累积发生率、PGF、移植物抗宿主病(GVHD)、病毒感染、总生存(OS)、无病生存(DFS)、复发、非复发死亡率(NRM)与 DSA 阴性组无差异(P>0.05)。多变量分析显示疾病缓解是 PGF 的保护因素(P=0.005,OR=0.019,95%CI 0.001-0.312)。亚组分析显示,无论 DSA 类型是针对 HLA-I 还是 II,MFI 值超过 5000 或不超过 5000,脱敏疗效均相等。总之,我们提出了一种基于免疫球蛋白的简单有效的 DSA 脱敏策略,以确保成功植入并改善患者预后。

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