Krauß Simon M, Telzerow Eva, Richter Daniel, Moret Anna S, Rothenberg-Thurley Maja, Sauerland Cristina, Weigert Anne, Fraccaroli Alessia, Tischer Johanna, Ziemann Frank, Götze Katharina S, Berdel Wolfgang E, Wörmann Bernhard, Krug Utz, Braess Jan, Heussner Pia, Enard Wolfgang, Hiddemann Wolfgang, Spiekermann Karsten, Görlich Dennis, Platzbecker Uwe, Metzeler Klaus H
Department of Hematology, Cell Therapy, Hemostaseology and Infectiology University of Leipzig Medical Center Leipzig Germany.
Department of Medicine III, University Hospital Ludwig-Maximilians-Universität München Munich Germany.
Hemasphere. 2025 Jul 24;9(7):e70183. doi: 10.1002/hem3.70183. eCollection 2025 Jul.
Clonal hematopoiesis (CH) is common in the general population and associated with various health risks, but its prevalence and clinical implications in acute myeloid leukemia (AML) long-term survivors (LTS; ≥5-year survival) are unknown. We analyzed CH in 373 AML-LTS with a median 11.6-year follow-up from diagnosis using a sensitive targeted sequencing assay based on single-molecule molecular inversion probes. CH variants were detected in 61.9% of survivors, with 26% having small-clone CH (SC-CH, variant allele frequency (VAF) < 2%) and 35.9% CH of indeterminate potential (≥2% VAF). CH was more prevalent in survivors treated with chemotherapy only (75.7%) compared to those who received allogeneic stem cell transplantation (alloSCT, 54.0%) and to age group-matched healthy controls. In chemotherapy-treated survivors, CH prevalence increased with age, whereas in alloSCT recipients, it most closely associated with hematopoietic age (i.e., the sum of donor age and time since transplantation). The variant spectrum also differed by treatment, with and variants being more common in the chemotherapy group. CH variants ≥10% VAF associated with increased risks of diabetes in alloSCT recipients and secondary neoplasms in chemotherapy-treated survivors. This study provides insights into the high prevalence and potential clinical relevance of CH in AML-LTS.
克隆性造血（CH）在普通人群中很常见，且与多种健康风险相关，但其在急性髓系白血病（AML）长期存活者（LTS；存活≥5年）中的患病率及临床意义尚不清楚。我们使用基于单分子分子倒置探针的敏感靶向测序分析方法，对373例AML-LTS患者进行了CH分析，从诊断开始的中位随访时间为11.6年。在61.9%的存活者中检测到CH变异，其中26%为小克隆CH（SC-CH，变异等位基因频率（VAF）<2%），35.9%为潜在不确定的CH（VAF≥2%）。与接受异基因干细胞移植（alloSCT，54.0%）的患者以及年龄匹配的健康对照相比，仅接受化疗的存活者中CH更为普遍（75.7%）。在接受化疗的存活者中，CH患病率随年龄增加而升高，而在alloSCT受者中，它与造血年龄（即供者年龄与移植后时间之和）最为密切相关。变异谱也因治疗方式而异， 和 变异在化疗组中更为常见。VAF≥10%的CH变异与alloSCT受者患糖尿病的风险增加以及接受化疗的存活者发生继发性肿瘤的风险增加相关。本研究为CH在AML-LTS中的高患病率及潜在临床相关性提供了见解。
