Clonal hematopoiesis (CH) mutations are common among individuals without known hematologic disease. CH mutations have been associated with numerous adverse clinical outcomes across many different studies. We systematically reviewed the available literature for clinical outcomes associated with CH mutations in patients without hematologic disease. We searched PubMed, EMBASE, and Scopus for eligible studies. Three investigators independently extracted the data, and each study was verified by a second author. Risk of bias was assessed using the Newcastle-Ottawa Scale. We identified 32 studies with 56 cohorts that examine the association between CH mutations and clinical outcomes. We conducted meta-analyses comparing outcomes among individuals with and without detectable CH mutations. We conducted meta-analyses for cardiovascular diseases (nine studies; HR = 1.61, 95% CI = 1.26–2.07, p = .0002), hematologic malignancies (seven studies; HR = 5.59, 95% CI = 3.31–9.45, p < .0001), therapy-related myeloid neoplasms (four studies; HR = 7.55, 95% CI = 4.3–13.57, p < .001), and death (nine studies; HR = 1.34, 95% CI = 1.2–1.5, p < .0001). The cardiovascular disease analysis was further stratified by variant allele fraction (VAF) and gene, which showed a statistically significant association only with a VAF of ≥ 10% (HR = 1.42, 95% CI = 1.24–1.62, p < .0001), as well as statistically significant associations for each gene examined with the largest magnitude of effect found for CH mutations in JAK2 (HR = 3.5, 95% CI = 1.84–6.68, p < .0001). Analysis of the association of CH mutations with hematologic malignancy demonstrated a numeric stepwise increase in risk with increasing VAF thresholds. This analysis strongly supports the association of CH mutations with a clinically meaningful increased risk of adverse clinical outcomes among individuals without hematologic disease, particularly with increasing VAF thresholds.

中文翻译：

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克隆性造血突变与临床结果的关联：系统评价和荟萃分析

克隆性造血 (CH) 突变在没有已知血液病的个体中很常见。在许多不同的研究中，CH 突变与许多不良临床结果有关。我们系统地回顾了与无血液病患者 CH 突变相关的临床结果的现有文献。我们在 PubMed、EMBASE 和 Scopus 中搜索了符合条件的研究。三名研究者独立提取数据，每项研究均由第二作者验证。使用纽卡斯尔-渥太华量表评估偏倚风险。我们确定了 56 个队列的 32 项研究，这些研究检查了 CH 突变与临床结果之间的关联。我们进行了荟萃分析，比较有和没有可检测到的 CH 突变的个体的结果。p  = .0002），血液系统恶性肿瘤（七项研究；HR = 5.59，95% CI = 3.31–9.45，p  < .0001），治疗相关的骨髓肿瘤（四项研究；HR = 7.55，95% CI = 4.3–13.57 , p  < .001）和死亡（九项研究；HR = 1.34，95% CI = 1.2–1.5，p  < .0001）。心血管疾病分析通过变异等位基因分数 (VAF) 和基因进一步分层，显示仅与 VAF ≥ 10%（HR = 1.42，95% CI = 1.24–1.62， p <.0001）具有统计学显着相关性 ，以及在JAK2中发现的 CH 突变影响最大的每个基因的统计显着关联（HR = 3.5, 95% CI = 1.84–6.68, p <.0001)。对 CH 突变与血液恶性肿瘤的关联分析表明，随着 VAF 阈值的增加，风险呈数字逐步增加。该分析强烈支持 CH 突变与没有血液病的个体不良临床结果风险增加的临床意义相关，特别是随着 VAF 阈值的增加。