Increased clonal hematopoiesis in long-term survivors of pediatric hematopoietic cell transplantation.

IF 11.5 Q1 HEMATOLOGY

Blood Cancer Discovery Pub Date : 2025-01-13 DOI:10.1158/2643-3230.BCD-24-0136

Konradin F Müskens, Nienke Wieringa, Maaike G J M van Bergen, Joëll E Bense, Brigit M Te Pas, Anne P J de Pagter, Arjan C Lankester, Marc B Bierings, Donna S Neuberg, Saskia Haitjema, Leontien C M Kremer, Gerwin A Huls, Stefan Nierkens, Joop H Jansen, Caroline A Lindemans, Aniek O de Graaf, Mirjam E Belderbos

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Abstract

In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. Here, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 non-transplanted controls. CH was detected in 16% of HCT recipients and 8% of controls, at variant allele frequencies (VAFs) of 0.01-0.31. Mutations were predominantly in DNMT3A (80%) and TET2 (20%). Older hematopoietic age (odds ratio: 1.07, p<0.001) and the HCT procedure (odds ratio: 2.53, p=0.02) independently increased the risk of CH, indicating both aging- and transplantation-induced effects. Large clones (VAF >0.10) were found exclusively in HCT recipients. Notably, CH was also detected within 15 years after a cord blood HCT. Inflammatory processes around graft infusion were associated with CH presence. Future studies are required to track the evolution of post-transplant CH and its impact on future cardiovascular disease, second malignancies and overall survival.

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儿童造血细胞移植长期存活患者克隆造血能力增加。

在儿童造血细胞移植（HCT）接受者中，移植的供体细胞可能需要远远超过正常人类寿命的功能。在这里，我们调查了144名儿童长期HCT幸存者和258名非移植对照组的克隆造血（CH）风险。在16%的HCT受体和8%的对照组中检测到CH，变异等位基因频率（VAFs）为0.01-0.31。突变主要发生在DNMT3A（80%）和TET2（20%）。造血年龄较大（优势比：1.07,p0.10）仅在HCT接受者中发现。值得注意的是，脐带血HCT后15年内也能检测到CH。移植物输注周围的炎症过程与CH的存在有关。未来的研究需要追踪移植后CH的演变及其对未来心血管疾病、第二恶性肿瘤和总生存率的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Blood Cancer Discovery Multiple-

CiteScore

12.70

自引率

1.80%

发文量

139

期刊介绍： The journal Blood Cancer Discovery publishes high-quality Research Articles and Briefs that focus on major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The topics covered include molecular and cellular features of pathogenesis, therapy response and relapse, transcriptional circuits, stem cells, differentiation, microenvironment, metabolism, immunity, mutagenesis, and clonal evolution. These subjects are investigated in both animal disease models and high-dimensional clinical data landscapes. The journal also welcomes submissions on new pharmacological, biological, and living cell therapies, as well as new diagnostic tools. They are interested in prognostic, diagnostic, and pharmacodynamic biomarkers, and computational and machine learning approaches to personalized medicine. The scope of submissions ranges from preclinical proof of concept to clinical trials and real-world evidence. Blood Cancer Discovery serves as a forum for diverse ideas that shape future research directions in hematooncology. In addition to Research Articles and Briefs, the journal also publishes Reviews, Perspectives, and Commentaries on topics of broad interest in the field.