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克隆性造血的不定潜能在接受自体干细胞移植的儿科患者中较为罕见。

Clonal hematopoiesis of indeterminate potential is rare in pediatric patients undergoing autologous stem cell transplantation.

机构信息

Division of Pediatric Hematology and Oncology, Department of Pediatrics, Inselspital, University Hospital, University of Bern, Bern, Switzerland.

Department for BioMedical Research, University of Bern, Bern, Switzerland.

出版信息

Pediatr Hematol Oncol. 2024 Oct;41(7):530-539. doi: 10.1080/08880018.2024.2362885. Epub 2024 Jun 6.

Abstract

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 in one patient no other variants indicative of CHIP were identified. As a CHIP-unrelated finding, germline variants in and in 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.

摘要

克隆性造血不定潜能 (CHIP) 描述了健康个体血液中反复出现的体细胞基因突变,与更高的血液系统恶性肿瘤风险和更高的心血管疾病全因死亡率相关。CHIP 随年龄增长而增加,在接受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,细胞应激因素(如细胞毒性治疗)如何影响 CHIP 的发生和扩展尚不清楚。我们对 33 名主要患有实体瘤的接受 ASCT 的儿科患者进行了一项回顾性研究,以确定 CHIP 的存在。我们通过下一代测序分析了在细胞输注前经过几个周期化疗后 CD34+ 选择的外周血干细胞移植物,测序包括 18 个“CHIP 基因”。除了一名患者存在一个体细胞变异外,没有发现其他表明 CHIP 的变异。作为与 CHIP 无关的发现,在两名和四名患者中分别发现了 和 中的种系变异。总之,我们在接受 ASCT 的儿科癌症患者队列中未检测到“典型”的 CHIP 变异。然而,需要更多具有更大患者数量的研究来评估儿童环境中的化疗是否会导致 CHIP 发生率增加,以及在何时增加。

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