Prospective characterization of clonal hematopoiesis and its clinical associations in elderly patients.

Clonal hematopoiesis (CH) is characterized by the expansion of hematopoietic stem cell clones carrying somatic mutations that confer a proliferative advantage, encompassing conditions such as Clonal Hematopoiesis of Indeterminate Potential (CHIP) and Clonal Cytopenia of Undetermined Significance (CCUS), each with varying clinical implications. This prospective 8-year cohort study of 173 patients investigated the prevalence, clinical outcomes, and genetic evolution of CHIP and CCUS in individuals over 75 years of age without prior hematologic disease, analyzing mortality rates, changes in allelic frequency over time, clinical characteristics, and associations with comorbidities such as osteoporosis, cardiovascular disease, and cancer. Through next-generation sequencing of 173 patients, we identified a 30.6% prevalence of CH, with DNMT3A, TET2, and ASXL1 as the most frequently mutated genes. While no significant associations were found between CH and cardiovascular disease or overall cytopenias, CH was correlated with a higher prevalence of osteoporosis, and high-risk CH was associated with cytopenias. Although not statistically significant (p = 0.09), survival curves suggested a potential trend toward higher mortality among patients with clonal hematopoiesis, supporting the need for further investigation in larger cohorts.