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造血干细胞移植中的克隆性造血。

Clonal hematopoiesis in hematopoietic stem cell transplantation.

机构信息

Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.

出版信息

Curr Opin Hematol. 2021 Mar 1;28(2):94-100. doi: 10.1097/MOH.0000000000000631.

Abstract

PURPOSE OF REVIEW

Clonal hematopoiesis (CH) is characterized by the acquisition of somatic mutations and subsequent expansion of mutated hematopoietic stem and progenitor cell (HSPC) clones without clinical evidence for a hematologic neoplasm. The prevalence of CH continuously increases with age reaching double-digit percentages in individuals >60 years. CH is associated with an increased risk for hematologic neoplasms and cardiovascular disease. We will review recent efforts to investigate how CH influences patient outcomes in hematopoietic stem cell transplantation - both autologous (ASCT) and allogeneic (allo-HSCT).

RECENT FINDINGS

Donor-engrafted CH is common in allo-HSCT recipients. Apart from a higher incidence of chronic GvHD and the rare but devastating complication of donor-derived leukemia, CH does not appear to negatively impact outcomes in allo-HSCT recipients. In lymphoma patients undergoing ASCT, however, CH is associated with an excess mortality driven by therapy-related myeloid neoplasms and cardiovascular events. Interestingly, inferior overall survival in patients with CH undergoing ASCT for multiple myeloma (MM) is due to an increased rate of MM progression.

SUMMARY

CH is highly prevalent in both allo-HSCT and ASCT patients suggesting a clinically relevant but context-dependent impact on adverse outcomes. Given the current lack of therapeutic interventions, systematic screening for CH in the transplant setting is currently not indicated outside of clinical studies.

摘要

目的综述

克隆性造血(CH)的特征是获得体细胞突变,并随后扩增突变的造血干细胞和祖细胞(HSPC)克隆,而没有血液系统恶性肿瘤的临床证据。CH 的患病率随着年龄的增长而持续增加,在 >60 岁的个体中达到两位数的百分比。CH 与血液系统恶性肿瘤和心血管疾病的风险增加有关。我们将回顾最近的研究努力,以调查 CH 如何影响造血干细胞移植(自体移植[ASCT]和异基因[allo-HSCT])患者的结局。

最近的发现

供体植入的 CH 在 allo-HSCT 受者中很常见。除了慢性 GvHD 的发生率更高和供体衍生白血病这一罕见但具有破坏性的并发症外,CH 似乎不会对 allo-HSCT 受者的结局产生负面影响。然而,在接受 ASCT 的淋巴瘤患者中,CH 与治疗相关的髓系肿瘤和心血管事件导致死亡率过高。有趣的是,在接受 ASCT 治疗多发性骨髓瘤(MM)的患者中,CH 导致总体生存率降低的原因是 MM 进展率增加。

总结

CH 在 allo-HSCT 和 ASCT 患者中均高度流行,这表明其对不良结局有临床相关但与背景相关的影响。鉴于目前缺乏治疗干预措施,除了临床试验之外,在移植环境中对 CH 进行系统筛查目前并不指征。

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