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异基因造血细胞移植后的免疫监测:迈向实用指南与标准化

Immune Monitoring After Allogeneic Hematopoietic Cell Transplantation: Toward Practical Guidelines and Standardization.

作者信息

Boelens Jaap Jan, Hosszu Kinga K, Nierkens Stefan

机构信息

Stem Cell Transplantation and Cellular Therapies, MSK Kids, Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Princess Máxima Center for Pediatric Oncology and UMC Utrecht, Utrecht, Netherlands.

出版信息

Front Pediatr. 2020 Aug 21;8:454. doi: 10.3389/fped.2020.00454. eCollection 2020.

Abstract

Hematopoietic cell transplantation (HCT) is often a last resort, but potentially curative treatment option for children suffering from hematological malignancies and a variety of non-malignant disorders, such as bone marrow failure, inborn metabolic disease or immune deficiencies. Although efficacy and safety of the HCT procedure has increased significantly over the last decades, the majority of the patients still suffer from severe acute toxicity, viral reactivation, acute or chronic graft-versus-host disease (GvHD) and/or, in case of malignant disease, relapses. Factors influencing HCT outcomes are numerous and versatile. For example, there is variation in the selected graft sources, type of infused cell subsets, cell doses, and the protocols used for conditioning, as well as immune suppression and treatment of adverse events. Moreover, recent pharmacokinetic studies show that medications used in the conditioning regimen (e.g., busulphan, fludarabine, anti-thymocyte globulin) should be dosed patient-specific to achieve optimal exposure in every individual patient. Due to this multitude of variables and site-specific policies/preferences, harmonization between HCT centers is still difficult to achieve. Literature shows that adequate immune recovery post-HCT limits both relapse and non-relapse mortality (death due to viral reactivations and GvHD). Monitoring immune parameters post-HCT may facilitate a timely prediction of outcome. The use of standardized assays to measure immune parameters would facilitate a fast comparison between different strategies tested in different centers or between different clinical trials. We here discuss immune cell markers that may contribute to clinical decision making and may be worth to standardize in multicenter collaborations for future trials.

摘要

造血细胞移植(HCT)通常是最后的手段,但对于患有血液系统恶性肿瘤以及各种非恶性疾病(如骨髓衰竭、先天性代谢疾病或免疫缺陷)的儿童来说,却是一种可能治愈的治疗选择。尽管在过去几十年中,HCT程序的疗效和安全性有了显著提高,但大多数患者仍遭受严重的急性毒性、病毒再激活、急性或慢性移植物抗宿主病(GvHD),和/或(在恶性疾病的情况下)复发。影响HCT结果的因素众多且多样。例如,所选移植物来源、输注细胞亚群类型、细胞剂量、预处理方案以及免疫抑制和不良事件治疗方面存在差异。此外,最近的药代动力学研究表明,预处理方案中使用的药物(如白消安、氟达拉滨、抗胸腺细胞球蛋白)应根据患者个体情况给药,以在每个患者中实现最佳暴露。由于存在如此多的变量以及特定地点的政策/偏好,HCT中心之间的协调仍然难以实现。文献表明,HCT后充分的免疫恢复可限制复发和非复发死亡率(因病毒再激活和GvHD导致的死亡)。监测HCT后的免疫参数可能有助于及时预测结果。使用标准化检测方法来测量免疫参数将有助于快速比较在不同中心测试的不同策略或不同临床试验之间的结果。我们在此讨论可能有助于临床决策且可能值得在多中心合作中进行标准化以供未来试验使用的免疫细胞标志物。

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