Kongtim Piyanuch, Vittayawacharin Pongthep, Zou Jun, Srour Samer, Shaffer Brian, Shapiro Roman M, Varma Ankur, McGuirk Joseph, Dholaria Bhagirathbhai R, McCurdy Shannon R, DeZern Amy E, Bejanyan Nelli, Bashey Asad, Furst Sabine, Castagna Luca, Mariotti Jacopo, Ruggeri Annalisa, Bailen Rebeca, Teshima Takanori, Xiao-Jun Huang, Bonfim Carmen, Aung Fleur, Cao Kai, Carpenter Paul A, Hamadani Mehdi, Askar Medhat, Fernandez-Vina Marcelo, Girnita Alin, Ciurea Stefan O
Hematopoietic Stem Cell Transplant and Cellular Therapy Program, Division of Hematology and Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA.
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Transplant Cell Ther. 2024 Dec;30(12):1139-1154. doi: 10.1016/j.jtct.2024.09.005. Epub 2024 Sep 10.
Donor-specific anti-HLA antibodies (DSA) are an important cause of engraftment failure and may negatively impact survival outcomes of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) using an HLA-mismatched allograft. The incidence of DSA varies across studies, depending on individual factors, detection or identification methods and thresholds considered clinically relevant. Although DSA testing by multiplex bead arrays remains semiquantitative, it has been widely adopted as a standard test in most transplant centers. Additional testing to determine risk of allograft rejection may include assays with HLA antigens in natural conformation, such as flow cytometric crossmatch, and/or antibody binding assays, such as C1q testing. Patients with low level of DSA (<2,000 mean fluorescence intensity; MFI) may not require treatment, while others with very high level of DSA (>20,000 MFI) may be at very high-risk for engraftment failure despite current therapies. By contrast, in patients with moderate or high level of DSA, desensitization therapy can successfully mitigate DSA levels and improve donor cell engraftment rate, with comparable outcomes to patients without DSA. Treatment is largely empirical and multimodal, involving the removal, neutralization, and blocking of antibodies, as well as inhibition of antibody production to prevent activation of the complement cascade. Desensitization protocols are based on accumulated multicenter experience, while prospective multicenter studies remain lacking. Most patients require a full intensity protocol that includes plasma exchange, while protocols relying only on rituximab and intravenous immunoglobulin may be sufficient for patients with lower DSA levels and negative C1q and/or flow cytometric crossmatch. Monitoring DSA levels before and after HSCT could guide preemptive treatment when high levels persist after stem cell infusion. This paper aims to standardize current evidence-based practice and formulate future directions to improve upon current knowledge and advance treatment for this relatively rare, but potentially serious complication in allogeneic HSCT recipients.
供者特异性抗人白细胞抗原抗体（DSA）是移植失败的重要原因，可能会对接受 HLA 配型不合的同种异体造血干细胞移植（HSCT）患者的生存结局产生负面影响。DSA 的发生率因研究而异，取决于个体因素、检测或鉴定方法以及临床相关阈值。尽管采用多重微珠阵列进行 DSA 检测仍为半定量检测，但在大多数移植中心已被广泛用作标准检测方法。用于确定移植排斥风险的其他检测可能包括天然构象 HLA 抗原检测，如流式细胞术交叉配型，和/或抗体结合检测，如 C1q 检测。DSA 水平较低（平均荧光强度<2000；MFI）的患者可能无需治疗，而其他 DSA 水平非常高（>20000 MFI）的患者，尽管目前有治疗方法，但其移植失败风险可能非常高。相比之下，对于 DSA 水平为中度或高度的患者，脱敏治疗可以成功降低 DSA 水平并提高供体细胞植入率，其结局与无 DSA 的患者相当。治疗主要基于经验且为多模式，包括清除、中和及阻断抗体，以及抑制抗体产生以防止补体级联反应激活。脱敏方案基于多中心积累的经验，但前瞻性多中心研究仍然缺乏。大多数患者需要包括血浆置换的全强度方案，而仅依赖利妥昔单抗和静脉注射免疫球蛋白的方案可能足以用于 DSA 水平较低且 C1q 和/或流式细胞术交叉配型为阴性的患者。在 HSCT 前后监测 DSA 水平，当干细胞输注后高水平持续存在时可指导抢先治疗。本文旨在规范当前基于证据的实践，并制定未来方向，以完善当前知识并推进对同种异体 HSCT 受者中这种相对罕见但可能严重的并发症的治疗。
