SOHO State of the Art Updates and Next Questions | Progress in Clonal Hematopoiesis of Indeterminate Potential/Clonal Cytopenia of Uncertain Significance.

Clonal hematopoiesis (CH) refers to the acquisition of somatic mutations in hematopoietic cells, which confers a risk of progression to myeloid malignancy, cardiovascular disease, and increased mortality. More widespread availability of next-generation sequencing has resulted in increased detection of CH, raising important clinical questions in the field regarding diagnostic criteria, prognostication, and therapeutic strategies. While the traditional definition of CH requires mutations to have a variant allele frequency of at least 2%, emerging data suggest that clinical impact may be mutation-specific. Some mutations, such as JAK2, CALR, TET2, and DNMT3A, may result in increased nonhematologic risks, such as increased risk of venous thromboembolism or atherosclerosis at variant allele frequencies below 2%. Multiple prognostic models have been developed since 2023, including the Clonal Hematopoiesis Risk Score, MN-Predict, and Clonal Cytopenia Risk Score. These models primarily aim to predict the risk of myeloid neoplasm, and further development is needed to better predict nonhematologic outcomes. While management of CH primarily consists of surveillance based on risk stratification, promising clinical trials are underway, including with anti-inflammatory agents and targeted therapies. Overall, the significant progress in this field appears promising, with a pathway to prevent malignancy and improve patient outcomes.