Association of clonal hematopoiesis mutations with clinical outcomes: A systematic review and meta-analysis.
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
07
01
2022
received:
22
10
2021
accepted:
09
01
2022
pubmed:
12
1
2022
medline:
30
4
2022
entrez:
11
1
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35015316
doi: 10.1002/ajh.26465
pmc: PMC9284564
mid: NIHMS1821781
doi:
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
411-420Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : NCI K08CA263313
Pays : United States
Organisme : NCI NIH HHS
ID : L30 CA253796
Pays : United States
Organisme : NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA263313
Pays : United States
Organisme : NCI NIH HHS
ID : NCI L30CA253796
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA241318
Pays : United States
Informations de copyright
© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
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