在接受自体干细胞移植的儿童患者中,具有不确定潜能的克隆性造血非常罕见。

IF 1.2 4区 医学 Q4 HEMATOLOGY
Pediatric Hematology and Oncology Pub Date : 2024-10-01 Epub Date: 2024-06-06 DOI:10.1080/08880018.2024.2362885
Mutlu Kartal-Kaess, Axel Karow, Ulrike Bacher, Thomas Pabst, Raphael Joncourt, Christiane Zweier, Claudia E Kuehni, Naomi Azur Porret, Jochen Roessler
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引用次数: 0

摘要

不确定潜能克隆造血(CHIP)是指健康人血液中反复出现的体细胞基因突变,与较高的血液恶性肿瘤风险和较高的心血管疾病全因死亡率有关。CHIP随年龄增长而增加,在癌症化疗或放疗后的成年患者中更为常见。此外,在一些接受自体干细胞移植(ASCT)或其后的成年患者中,也发现了CHIP。在儿童和青少年中,细胞毒性治疗等细胞应激因素如何影响CHIP的发生率和扩大,目前仍不清楚。我们对 33 名主要患有实体瘤、接受 ASCT 的儿童患者进行了一项回顾性研究,以确定是否存在 CHIP。在细胞输注前,我们对经过几个化疗周期的CD34+外周血干细胞移植物进行了下一代测序分析,其中包括18个 "CHIP基因"。除了一名患者体内的TP53体细胞变异外,没有发现其他表明CHIP的变异。在两名患者和四名患者中,分别发现了 CHEK2 和 ATM 的种系变异,这与 CHIP 无关。总之,我们无法在接受 ASCT 的儿童癌症患者中检测到 "典型的 "CHIP 变异。不过,有必要进行更多患者人数更多的研究,以评估儿科化疗是否会导致CHIP发病率增加,以及在什么时间点上会导致CHIP发病率增加。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clonal hematopoiesis of indeterminate potential is rare in pediatric patients undergoing autologous stem cell transplantation.

Clonal hematopoiesis of indeterminate potential (CHIP) describes recurrent somatic gene mutations in the blood of healthy individuals, associated with higher risk for hematological malignancies and higher all-cause mortality by cardiovascular disease. CHIP increases with age and is more common in adult patients after chemotherapy or radiation for cancer. Furthermore, in some adult patients undergoing autologous stem cell transplantation (ASCT) or thereafter, CHIP has been identified. In children and adolescents, it remains unclear how cellular stressors such as cytotoxic therapy influence the incidence and expansion of CHIP. We conducted a retrospective study on 33 pediatric patients mostly with solid tumors undergoing ASCT for presence of CHIP. We analyzed CD34+ selected peripheral blood stem cell grafts after several cycles of chemotherapy, prior to cell infusion, by next-generation sequencing including 18 "CHIP-genes". Apart from a somatic variant in TP53 in one patient no other variants indicative of CHIP were identified. As a CHIP-unrelated finding, germline variants in CHEK2 and in ATM were identified in two and four patients, respectively. In conclusion, we could not detect "typical" CHIP variants in our cohort of pediatric cancer patients undergoing ASCT. However, more studies with larger patient numbers are necessary to assess if chemotherapy in the pediatric setting contributes to an increased CHIP incidence and at what time point.

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来源期刊
CiteScore
2.60
自引率
5.90%
发文量
71
审稿时长
6-12 weeks
期刊介绍: PHO: Pediatric Hematology and Oncology covers all aspects of research and patient management within the area of blood disorders and malignant diseases of childhood. Our goal is to make PHO: Pediatric Hematology and Oncology the premier journal for the international community of clinicians and scientists who together aim to define optimal therapeutic strategies for children and young adults with cancer and blood disorders. The journal supports articles that address research in diverse clinical settings, exceptional case studies/series that add novel insights into pathogenesis and/or clinical care, and reviews highlighting discoveries and challenges emerging from consortia and conferences. Clinical studies as well as basic and translational research reports regarding cancer pathogenesis, genetics, molecular diagnostics, pharmacology, stem cells, molecular targeting, cellular and immune therapies and transplantation are of interest. Papers with a focus on supportive care, late effects and on related ethical, legal, psychological, social, cultural, or historical aspects of these fields are also appreciated. Reviews on important developments in the field are welcome. Articles from scientists and clinicians across the international community of Pediatric Hematology and Oncology are considered for publication. The journal is not dependent on or connected with any organization or society. All submissions undergo rigorous peer review prior to publication. Our Editorial Board includes experts in Pediatric Hematology and Oncology representing a wide range of academic and geographic diversity.
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