TY - JOUR
T1 - Association of clonal hematopoiesis mutations with clinical outcomes
T2 - A systematic review and meta-analysis
AU - Nowakowska, Malgorzata K.
AU - Kim, Taebeom
AU - Thompson, Mikayla T.
AU - Bolton, Kelly L.
AU - Deswal, Anita
AU - Lin, Steven H.
AU - Scheet, Paul
AU - Wehner, Mackenzie R.
AU - Nead, Kevin T.
N1 - Publisher Copyright:
© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85122881095&partnerID=8YFLogxK
U2 - 10.1002/ajh.26465
DO - 10.1002/ajh.26465
M3 - Article
C2 - 35015316
AN - SCOPUS:85122881095
SN - 0361-8609
VL - 97
SP - 411
EP - 420
JO - American journal of hematology
JF - American journal of hematology
IS - 4
ER -