Clonal expansions in the hematopoietic system, referred to as clonal hematopoiesis (CH), is common throughout life and associated with significant clinical outcomes, including increased risk of hematologic cancers, all-cause mortality and nonmalignant conditions. Recently, clinical definitions of disorders within the spectrum of CH have been introduced, including clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS), providing the framework for harmonized classification and registration. However, while clone features and dynamics have been well described, relevant key issues remain to be clarified.

In the first presentation, Dr. Malcovati will provide an overview of biological underpinnings and clinical implications of CH. In addition, the spectrum of clonal cytopenias, as well as current classification framework and its pitfalls, will be critically discussed. Finally, the contribution of intra- and extra-clonal factors to clonal evolution, and the models developed for predicting the risk of developing myeloid neoplasms and the trajectory of evolution will be reviewed, as a basis for informing early-detection and prevention strategies.

In the second presentation, Dr Grønbæk will discuss the clinical management of CH in everyday clinical practice, focusing on how individual/patients with CH are identified, including the incidental finding, which emphasizes the need for informed consent before sequencing. She will elaborate on the importance of identifying and following high-risk individuals/patients while sparing low risk individuals unnecessary worries. The importance of enrolling these individuals/patients in clinical trials will be discussed including the optimal trials designs. Examples of ongoing trials will be presented and critically appraised.