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接受达雷妥尤单抗治疗的输血患者中红细胞同种免疫的缺失:来自单一中心的经验

Absence of Red Blood Cell Alloimmunization in Transfused Patients Receiving Daratumumab: Experience from a Single Center.

作者信息

Eritzpokhoff Lara, Talegón De La Fuente Ernesto, Carril Barcia Aida, Asensi Cantó Pedro, Gómez Segui Ines, Arnao Herraiz Mario, De La Rubia Comos Javier, Solves Alcaina Pilar

机构信息

Blood Bank and Hematology Department, Hospital La Fe, 46026 Valencia, Spain.

CIBERONC, Instituto Carlos III, Fundación para la Investigación del Hospital Universitario y Politécnico La Fe de la Comunidad Valenciana, Hospital La Fe, 46026 Valencia, Spain.

出版信息

J Clin Med. 2025 Aug 14;14(16):5754. doi: 10.3390/jcm14165754.

DOI:10.3390/jcm14165754
PMID:40869587
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12386634/
Abstract

Daratumumab is an anti-CD38 monoclonal antibody used in the treatment of multiple myeloma. Its use interferes with the indirect antiglobulin test (IAT). Treatment of reagent red blood cells (RBCs) with dithiothreitol (DTT) is one of the most validated techniques to resolve this interference. The objective of this study is to evaluate the rate of alloimmunization in transfused patients receiving daratumumab and the occurrence of hemolytic transfusion reactions. We conducted a single-center, retrospective, descriptive analysis of all patients treated with daratumumab at our institution from October 2016 to April 2024. For daratumumab-treated patients requiring RBC transfusions, an IAT with DTT-pretreated RBCs (DTT-IAT) was performed using the automated Orthovision system. Transfusion was administered only with a previous negative DTT-IAT while respecting Rh and Kell phenotyping. We assessed the transfusion profile of our patient cohort, including their rates of alloimmunization before and after daratumumab initiation, as well as the incidence of hemolytic complications. Additionally, a literature review was performed on reported alloimmunization rates in daratumumab-treated patients. Among all patients, 106 received RBC and/or platelet transfusions after starting daratumumab. Four had known pre-existing alloantibodies. None developed new alloantibodies or experienced hemolytic complications while receiving anti-CD38 therapy. There were four cases of false-positive DTT-IAT due to residual drug interference or technical variability, in which no alloantibodies or adverse transfusion reactions were detected. Patients receiving daratumumab exhibit a low risk of alloimmunization. This may be partly explained by adherence to Rh and Kell phenotyping and daratumumab's immunosuppressive effects on alloantibody production. These results support the conclusion that an extended red blood cell phenotype or genotype before starting daratumumab could be omitted if a fast and reliable technique for pretransfusion testing (such as automated DTT-IAT) is available 24 h.

摘要

达雷妥尤单抗是一种用于治疗多发性骨髓瘤的抗CD38单克隆抗体。它的使用会干扰间接抗球蛋白试验(IAT)。用二硫苏糖醇(DTT)处理试剂红细胞(RBC)是解决这种干扰的最有效技术之一。本研究的目的是评估接受达雷妥尤单抗治疗的输血患者的同种免疫发生率和溶血性输血反应的发生情况。我们对2016年10月至2024年4月在本机构接受达雷妥尤单抗治疗的所有患者进行了单中心、回顾性、描述性分析。对于需要输注红细胞的达雷妥尤单抗治疗患者,使用自动Orthovision系统进行DTT预处理红细胞的IAT(DTT-IAT)。仅在之前DTT-IAT结果为阴性且符合Rh和Kell血型分型的情况下才进行输血。我们评估了患者队列的输血情况,包括达雷妥尤单抗开始使用前后的同种免疫发生率以及溶血并发症的发生率。此外,还对报道的达雷妥尤单抗治疗患者的同种免疫发生率进行了文献综述。在所有患者中,106例在开始使用达雷妥尤单抗后接受了红细胞和/或血小板输血。4例已知存在预先存在的同种抗体。在接受抗CD38治疗期间,没有患者产生新的同种抗体或发生溶血并发症。有4例假阳性DTT-IAT病例,原因是残留药物干扰或技术差异,未检测到同种抗体或不良输血反应。接受达雷妥尤单抗治疗的患者同种免疫风险较低。这可能部分归因于遵循Rh和Kell血型分型以及达雷妥尤单抗对同种抗体产生的免疫抑制作用。这些结果支持这样的结论:如果有快速可靠的输血前检测技术(如自动DTT-IAT)且可在24小时内获得,那么在开始使用达雷妥尤单抗之前可以省略扩展的红细胞表型或基因型检测。

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本文引用的文献

1
A Brief Report on Pre-Transfusion Testing in Patients Receiving the Anti-CD38 Monoclonal Antibody for Hematological Disorders in India.印度接受抗CD38单克隆抗体治疗血液系统疾病患者的输血前检测简要报告
Indian J Hematol Blood Transfus. 2024 Oct;40(4):710-714. doi: 10.1007/s12288-024-01763-5. Epub 2024 Apr 1.
2
Risk of new alloimmunization in patients on anti-CD38 treatment using tube LISS-IAT method.采用管型 LISS-IAT 方法治疗抗 CD38 患者的新同种免疫风险。
Transfus Apher Sci. 2024 Apr;63(2):103873. doi: 10.1016/j.transci.2024.103873. Epub 2024 Jan 12.
3
Efficient neutralization of daratumumab in pretransfusion samples using a novel recombinant monoclonal anti-idiotype antibody.使用新型重组单克隆抗独特型抗体在输血前样本中有效中和达雷妥尤单抗。
Transfusion. 2022 Aug;62(8):1511-1518. doi: 10.1111/trf.17006. Epub 2022 Jul 22.
4
Clinical Considerations for Immunoparesis in Multiple Myeloma.多发性骨髓瘤免疫球蛋白缺乏症的临床考量
Cancers (Basel). 2022 May 3;14(9):2278. doi: 10.3390/cancers14092278.
5
RBC alloimmunization and daratumumab: Are efforts to eliminate interferences and prevent new antibodies necessary?红细胞同种免疫与达雷妥尤单抗:是否有必要努力消除干扰并预防新抗体产生?
Transfusion. 2021 Dec;61(12):3283-3285. doi: 10.1111/trf.16736. Epub 2021 Nov 12.
6
Antibody incidence and red blood cell transfusions in patients on daratumumab.达雷妥尤单抗治疗患者的抗体发生率和红细胞输注情况。
Transfusion. 2021 Dec;61(12):3468-3472. doi: 10.1111/trf.16687. Epub 2021 Oct 7.
7
Alloimmunisation rate of patients on Daratumumab: A retrospective cohort study of patients in England.达雷妥尤单抗治疗患者的同种免疫发生率:一项英国患者的回顾性队列研究。
Transfus Med. 2021 Dec;31(6):474-480. doi: 10.1111/tme.12808. Epub 2021 Aug 17.
8
Optimizing transfusion management of multiple myeloma patients receiving daratumumab-based regimens.优化接受达雷妥尤单抗为基础方案治疗的多发性骨髓瘤患者的输血管理。
Transfusion. 2021 Jul;61(7):2054-2063. doi: 10.1111/trf.16425. Epub 2021 May 7.
9
CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity.CD38:炎症和自身免疫中的免疫调节分子。
Front Immunol. 2020 Nov 30;11:597959. doi: 10.3389/fimmu.2020.597959. eCollection 2020.
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Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR.达雷妥尤单抗、硼替佐米和地塞米松与硼替佐米和地塞米松治疗既往治疗的多发性骨髓瘤患者:CASTOR 的 3 年随访结果。
Clin Lymphoma Myeloma Leuk. 2020 Aug;20(8):509-518. doi: 10.1016/j.clml.2019.09.623. Epub 2019 Oct 9.