Diagnostic Challenge and Clinical Dilemma: The Long Reach of Clonal Hematopoiesis

Abstract

Abstract Background Widespread application of massively parallel sequencing has resulted in recognition of clonal hematopoiesis in various clinical settings and on a relatively frequent basis. Somatic mutations occur in individuals with normal blood counts, and increase in frequency with age. The genes affected are the same genes that are commonly mutated in overt myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This phenomenon is referred to as clonal hematopoiesis of indeterminate potential (CHIP). Content In this review, we explore the diagnostic and clinical implications of clonal hematopoiesis. In addition to CHIP, clonal hematopoiesis may be seen in patients with cytopenia who do not otherwise meet criteria for hematologic malignancy, a condition referred to as clonal cytopenia of undetermined significance (CCUS). Distinguishing CHIP and CCUS from overt myeloid neoplasm is a challenge to diagnosticians due to the overlapping mutational landscape observed in these conditions. We describe helpful laboratory and clinical features in making this distinction. CHIP confers a risk of progression to overt hematologic malignancy similar to other premalignant states. CHIP is also associated with a proinflammatory state with multisystem implications and increased mortality risk due to cardiovascular events. The current approach to follow up and management of patients with clonal hematopoiesis is described. Summary Nuanced understanding of clonal hematopoiesis is essential for diagnosis and clinical management of patients with hematologic conditions. Further data are needed to more accurately predict the natural history and guide management of these patients with respect to both malignant progression as well as nonhematologic sequelae.