Diagnostic Approach, Clinical Implications and Management of Clonal Cytopenia of Undetermined Significance

Abstract

Due to demographic aging of the general population, cytopenia and especially anemia of unknown origin is on the rise, with an increasing need for a structured clinical assessment of these conditions. The advent of next-generation sequencing (NGS) in our clinical practice has facilitated the detection of clonal hematopoiesis (CH), which is present in more than 20−40% of individuals above 80 years of age. This poses unprecedented challenges as CH, especially clonal cytopenia of undetermined significance (CCUS), is associated with the development of myeloid malignancies, cardiovascular diseases and other chronic inflammatory-degenerative conditions. CH comprises an array of entities that are distinct from overt myeloid malignancies, but consensus recommendations are currently lacking for the management of affected patients. Many questions remain unsolved, such as which patients with unclear cytopenia should undergo molecular testing, what distinguishes age-associated CH from overt hematological malignancy, how CH impacts comorbidities and what might be the most appropriate treatment plan. In this review, we provide a structured approach to the assessment of unclear cytopenia and summarize the clinical implications of CH, as well as our current management of CCUS patients.

Extinguishing the Fire of Inflammation in Clonal Hematopoiesis

“…2 For example, clonal hematopoiesis (CH) has emerged as an age-associated phenomenon characterized by the occurrence of single mutations in driver genes like TET2, DNMT3A or ASXL1 at low allele frequency. [3][4][5] Therefore, CH has the potential to reconstitute the full spectrum of quasi-normal hematopoietic differentiation. 6 Exogenous stressors (e.g., infections, tissue damage, inflammation) can lead to subtle functional changes that alter biological interactions during hematopoietic differentiation, resulting in a proinflammatory phenotype.…”