Work

76. Long term follow up of Clonal Hematopoiesis in a cohort of octogenarians: A prospective study

Year: 2025

Type: article

Abstract: Introduction 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), with varying clinical implications. This long-term prospective cohort study of 9 years investigated the prevalence, clinical outcomes, and genetic evolution of CHIP and CCUS in individuals over 75 years old without prior hematologic disease, analyzing mortality rates, changes in allelic frequency over time, clinical differences, and associations with comorbidities such as osteoporosis, cardiovascular disease, and cancer. Methods This prospective long term follow-up cohort study included 172 patients aged 75 or older, without a history of myeloid hematologic neoplasms. They were divided into two groups: Clonal Hematopoiesis (CH) with mutations and a variant allele frequency (VAF) > 2%, and No Clonal Hematopoiesis (No-CH) without mutations. Over 9 years (2016-2024), survival curves, clinical outcomes, and laboratory analyses, including blood counts and next-generation sequencing, were assessed. Results We identified a 30.8% prevalence of clonal hematopoiesis (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 linked to a higher prevalence of osteoporosis, reduction in survival rates and high-risk CH correlated with cytopenias - incluiding one CH patient with high-risk mutations that progressed to acute myeloid leukemia (AML) during the follow-up period. Discussion and Conclusion Our study revealed several key findings. We found that CH was not associated with cardiovascular diseases, suggesting a gene-specific link that warrants further investigation. Furthermore, no significant difference in serum troponin levels was observed between CH and no-CH patients, which can be explained by our study’s higher median age, considering that increased age is associated with a higher prevalence of cardiovascular and non-cardiac conditions that elevate baseline troponin levels in both groups. Also, we found no consistent pattern of increased variant allele frequency (VAF) over time, which contradicted our initial hypothesis of a progressive increase in VAF. Also, No significant difference in cytopenia prevalence was found between CH and no-CH groups, except in the high-risk CH subgroup (VAF >10%), highlighting the need for cautious interpretation of mutational screening, especially at lower VAFs. On the other hand, CH was associated with a statistically significant higher prevalence of osteoporosis in the CH group compared to the no-CH group, as well as a confirmed reduction in survival rates among elderly patients with CH, highlighting its clinical relevance in this population.

Source: Cancer Genetics

DOI: 10.1016/j.cancergen.2025.10.080