尽管新型放射性同位素治疗不断推动癌症护理进步，但对于治疗相关髓系肿瘤（t-MN）的报道引发了关注。这一过程中克隆造血系增生（CH）的患病率和作用仍待定义。我们假设：（1）复发性滤泡性淋巴瘤（FL）中CH普遍存在，并与t-MN转化相关；（2）放射治疗，以放射免疫治疗（RIT）为例，在克隆进展中发挥作用。在这个回顾性队列研究中，我们评估了接受RIT的58例严重预治疗FL患者中CH的患病率和预后影响对临床结果。患者在接受RIT之前接受了中位数为4线治疗。RIT之前CH的患病率为46%，而在配对样本中，RIT过程中和随后的治疗中的患病率为67%（p=0.15）。14例（24%）患者发展为t-MN。与无t-MN患者相比，t-MN患者具有更高的变异等位基因分数（38% vs. 15%，p=0.02）和克隆复杂性（p=0.03）。CH的谱系与与年龄相关的CH不同，存在高患病率的DNA损伤修复和响应途径突变，蛋白合成酶突变的缺失以及信号转导突变的缺乏。虽然RIT和t-MN之间及总生存率之间没有明显的临床关联，但t-MN患者具有更高的突变克隆负荷以及广泛的染色体异常（中位生存期为0.9个月）。CH的基线患病率很高，在接触到RIT和随后的治疗后患病率进一步增加。高t-MN发病率、高克隆复杂性和广泛的染色体损伤凸显了更好地鉴别和研究这些因素引发的遗传毒性应激的重要性。

While novel radioisotope therapies continue to advance cancer care, reports of therapy-related myeloid neoplasms (t-MN) have generated concern. The prevalence and role of clonal hematopoiesis (CH) in this process remain to be defined. We hypothesized that (1) CH is prevalent in relapsed follicular lymphoma (FL) and is associated with t-MN transformation. (2) Radiation in the form of radioimmunotherapy (RIT) plays a role in clonal progression. In this retrospective cohort study, we evaluated the prevalence and prognostic impact of CH on clinical outcomes in 58 heavily pre-treated FL patients who received RIT. Patients received a median of 4 lines of therapy before RIT. The prevalence of CH prior to RIT was 46%, while it was 67% (p=0.15) during the course of RIT and subsequent therapies in the paired samples. Fourteen (24%) patients developed t-MN. Patients with t-MN had a higher variant allele fraction (38% vs. 15%, p=0.02) and clonal complexity (p=0.03) than those without. The spectrum of CH differed from age-related CH, with a high prevalence of DNA damage repair and response pathway mutations, absence of spliceosome mutations, and a paucity of signaling mutations. While there were no clear clinical associations between RIT and t-MN, or overall survival, patients with t-MN had a higher mutant clonal burden, along with extensive chromosomal abnormalities (median survival 0.9 months). The baseline prevalence of CH is high, with a subsequent increase in prevalence on exposure to RIT and subsequent therapies. The high rates of t-MN with high clonal complexities and extensive chromosomal damage underscore the importance of better identifying and studying genotoxic stressors accentuated by these agents.