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病原体减少处理是否可作为辐照处理的替代方法,以降低输血相关移植物抗宿主病的风险?

Is pathogen reduction an acceptable alternative to irradiation for risk mitigation of transfusion-associated graft versus host disease?

机构信息

Cerus Corporation, 1220 Concord Avenue, Concord, CA, USA.

出版信息

Transfus Apher Sci. 2022 Apr;61(2):103404. doi: 10.1016/j.transci.2022.103404. Epub 2022 Mar 11.

DOI:10.1016/j.transci.2022.103404
PMID:35288055
Abstract

Transfusion-associated graft versus host disease (TA-GVHD) is a highly morbid and often fatal adverse event associated with transfusion of cellular blood products [platelets, red blood cells (RBCs) and whole blood] and more rarely with never-frozen plasma products. It is caused by residual viable donor T-lymphocytes that proliferate and actively target recipient tissues. Selective or universal irradiation of blood components using gamma-irradiation and more recently, X-ray irradiation, are the most commonly applied interventions and have been validated by the demonstration of in vitro T-lymphocyte inactivation, in murine models of TA-GVHD and by years of clinical experience. Irradiation, however, has multiple limitations including a sharp dose-response curve that renders quality control of dosage critically important, the use of radioactive radiation sources that are a terrorism risk, and selective implementation in many countries that leads to inadvertent omission and patient risk exposure. Certain pathogen reduction technologies (PRT) for platelets have been approved by regulatory authorities and endorsed by professional societies as an alternative to irradiation for reducing the risk of TA-GVHD, and PRT for RBCs and whole blood are in development. While the mechanism of action of T-lymphocyte inactivation differs from gamma/X-ray irradiation, the impact on T-lymphocyte inactivation for PRT is equivalent or superior to that of irradiation as demonstrated by sensitive in vitro lymphocyte proliferation assays and in vivo mouse models that approximate human TA-GVHD. Clinical trials and cumulative routine-use experience attest to the efficacy of PRT when used as an alternative to irradiation. While T-lymphocyte inactivation efficacy varies between PRT platforms, the implementation of PRT for platelets increases blood safety for patients beyond the mitigation of TA-GVHD, by decreasing the risk of transfusion transmitted infections with known viruses, bacteria and parasites as well as emerging pathogens.

摘要

输血相关移植物抗宿主病(TA-GVHD)是一种与细胞血液制品(血小板、红细胞(RBC)和全血)输注相关的高度病态和常致命的不良事件,更罕见的是与从未冷冻的血浆制品相关。它是由残留的有活力的供者 T 淋巴细胞增殖并主动靶向受者组织引起的。血液成分的选择性或普遍辐照,使用γ射线和最近的 X 射线辐照,是最常用的干预措施,并通过体外 T 淋巴细胞失活的证明、TA-GVHD 的小鼠模型以及多年的临床经验得到验证。然而,辐照有多种限制,包括剂量反应曲线陡峭,使得剂量的质量控制至关重要,使用放射性辐射源存在恐怖主义风险,以及在许多国家的选择性实施导致无意中遗漏和患者风险暴露。某些血小板病原体减少技术(PRT)已获得监管机构的批准,并被专业协会认可为降低 TA-GVHD 风险的辐照替代方法,用于 RBC 和全血的 PRT 正在开发中。虽然 T 淋巴细胞失活的作用机制与γ/X 射线辐照不同,但 PRT 对 T 淋巴细胞失活的影响与辐照相当或优于辐照,这已通过敏感的体外淋巴细胞增殖试验和模拟人类 TA-GVHD 的体内小鼠模型证明。临床试验和累积常规使用经验证明了 PRT 在替代辐照时的疗效。虽然 PRT 平台之间的 T 淋巴细胞失活效果不同,但血小板 PRT 的实施通过降低已知病毒、细菌和寄生虫以及新兴病原体的输血传播感染风险,增加了患者的血液安全性,超越了 TA-GVHD 的缓解。

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