School of Medicine, Baylor College of Medicine.
Department of Epidemiology, University of Texas MD Anderson Cancer Center.
Am J Hematol. 2022 Apr;97(4):411-420. doi: 10.1002/ajh.26465. Epub 2022 Jan 19.
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.
克隆性造血 (CH) 突变在无已知血液疾病的个体中很常见。CH 突变与许多不同研究中的许多不良临床结局相关。我们系统地回顾了有关无血液疾病患者的 CH 突变相关临床结局的现有文献。我们在 PubMed、EMBASE 和 Scopus 中搜索了合格的研究。三名调查员独立提取数据，每个研究都由第二名作者验证。使用纽卡斯尔-渥太华量表评估偏倚风险。我们确定了 32 项研究，其中 56 项研究检查了 CH 突变与临床结局之间的关系。我们进行了荟萃分析，比较了有和无可检测到的 CH 突变的个体之间的结局。我们对心血管疾病（9 项研究；HR = 1.61，95%CI = 1.26-2.07，p =.0002）、血液恶性肿瘤（7 项研究；HR = 5.59，95%CI = 3.31-9.45，p <.0001）、治疗相关髓系肿瘤（4 项研究；HR = 7.55，95%CI = 4.3-13.57，p <.001）和死亡（9 项研究；HR = 1.34，95%CI = 1.2-1.5，p <.0001）进行了荟萃分析。心血管疾病分析进一步按变异等位基因分数（VAF）和基因分层，仅当 VAF 为≥10%时，才显示出统计学上的显著相关性（HR = 1.42，95%CI = 1.24-1.62，p <.0001），以及每个基因的相关性分析显示，JAK2 中的 CH 突变的效应最大（HR = 3.5，95%CI = 1.84-6.68，p <.0001）。对 CH 突变与血液恶性肿瘤相关性的分析表明，随着 VAF 阈值的增加，风险呈数值递增。这项分析强烈支持 CH 突变与无血液疾病个体的不良临床结局相关的临床意义增加风险之间的关联，特别是随着 VAF 阈值的增加。
