Teipel Raphael, von Bonin Malte, Stölzel Friedrich, Schetelig Johannes, Thiede Christian, Bornhäuser Martin
Medizinische Klinik und Poliklinik 1, Universitätsklinikum Carl Gustav Carus an der TU Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland.
DKMS Clinical Trials Unit, Dresden, Deutschland.
Inn Med (Heidelb). 2022 Nov;63(11):1126-1132. doi: 10.1007/s00108-022-01403-y. Epub 2022 Sep 23.
The detection of clonal hematopoiesis (CH) in patients with hematologic neoplasms who are undergoing a cellular therapy is common. The most frequently used cellular therapy procedures include autologous and allogeneic hematopoietic stem cell transplantation (HSCT) and, more recently, chimeric antigen receptor (CAR) T‑cell therapy. All three procedures differ fundamentally in terms of harvesting and manufacturing aspects as well as usage of the respective cell product. Therefore, the importance of CH in relation to the respective treatment method must be evaluated and assessed differently. In autologous HSCT, the extent of previous cytotoxic therapy significantly contributes to the high prevalence of CH. The clinically most important aspect is the development of secondary neoplasms from a pre-existing CH clone and the potential risk for enhanced cardiovascular side effects. In allogeneic HSCT, the donor selection with respect to the age largely determines the probability for the presence of CH. In this setting, the development of secondary malignancies only plays a minor role compared to the autologous HSCT. In fact, the induction of a graft versus host (GvH) or a graft versus leukemia (GvL) effect and its influence on progression-free and overall survival seem to be of possible clinical relevance. The CAR T‑cell therapy is closely linked to inflammatory reactions regarding its mode of action and the associated side effects. In this context CH might be closely linked to the effectiveness and side effects of the CAR T‑cell therapy. Initial data reported a high prevalence of CH in patients before CAR T‑cell therapy and indicated an increased rate of inflammatory side effects, although no negative effect on survival has yet been demonstrated.
在接受细胞治疗的血液系统肿瘤患者中，克隆性造血（CH）的检测很常见。最常用的细胞治疗程序包括自体和异基因造血干细胞移植（HSCT），以及最近的嵌合抗原受体（CAR）T细胞疗法。这三种程序在采集、制造方面以及各自细胞产品的使用上有根本差异。因此，必须对CH与各自治疗方法相关的重要性进行不同的评估。在自体HSCT中，先前细胞毒性治疗的程度显著导致了CH的高患病率。临床上最重要的方面是由预先存在的CH克隆发展为继发性肿瘤以及心血管副作用增强的潜在风险。在异基因HSCT中，供体年龄的选择在很大程度上决定了CH存在的可能性。在这种情况下，与自体HSCT相比，继发性恶性肿瘤的发生只起次要作用。事实上，移植物抗宿主（GvH）或移植物抗白血病（GvL）效应的诱导及其对无进展生存期和总生存期的影响似乎具有可能的临床相关性。CAR T细胞疗法在其作用方式和相关副作用方面与炎症反应密切相关。在这种情况下，CH可能与CAR T细胞疗法的有效性和副作用密切相关。初步数据报告了CAR T细胞治疗前患者中CH的高患病率，并表明炎症副作用发生率增加，尽管尚未证明对生存有负面影响。
