The Broad-Ranging Impact of Clonal Hematopoiesis: From Diagnostic Considerations to Clinical Implications

Course overview

Premalignant clonal hematopoiesis refers to a heterogeneous group of conditions, including clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). CCUS is defined by expansion of a population of hematopoietic cells derived from a single clone, as demonstrated by the detection of myeloid neoplasm-associated somatic mutation or cytogenetic aberration (i.e., clonal hematopoiesis) in association with sustained cytopenia otherwise clinically unexplained and absence of dysplasia. CHIP is a closely related entity defined by the presence of clonal hematopoiesis in the absence of cytopenia. In both conditions, diagnostic criteria of myelodysplastic or other hematologic neoplasm are unmet. The natural history and risk of progression from clonal hematopoiesis to overt malignancy is augmented by mutational dynamics. Substantial data links CHIP to increased all-cause mortality primarily attributable to cardiovascular disease such as myocardial infarction, ischemic stroke, and venous thrombosis. The principal feature underlying these nonhematologic disease associations is a proinflammatory state. Clinical management of patients with clonal hematopoiesis is an area of active investigation. Learning Objectives: Summarize the molecular genetic basis of premalignant clonal hematopoiesis; Apply data-driven diagnostic concepts to distinguish patients with bona fide hematologic malignancy from individuals with clonal hematopoiesis; Describe the range of clinical implications associated with these precursor conditions and discuss emerging approaches to management