How I manage patients with unexplained cytopenia

Abstract The term “unexplained cytopenia” is used to describe a condition characterized by peripheral blood cytopenia that cannot be attributed to identifiable causes using conventional tests or to any concomitant diseases. Unexplained cytopenia requires clinical attention and further investigation to identify individuals at risk of developing a hematologic neoplasm. The available evidence suggests that somatic mutation analysis may effectively complement the diagnostic workup and clinical management of unexplained cytopenia. Indeed, the presence or absence of somatic mutation(s) in myeloid genes shows high positive and negative predictive values for myeloid neoplasms (MNs). Mutation analysis is also crucial for identifying patients with clonal cytopenia of undetermined significance (CCUS), a condition at increased risk of developing a MN. Recently, clinical/molecular prognostic models have been developed, providing valuable tools for the personalization of clinical and molecular surveillance. Most patients with CCUS show mild cytopenia and do not require therapeutic intervention. Currently, there is no treatment approved for CCUS, and transfusion therapy is the sole therapeutic option for patients with severe symptomatic cytopenia. However, this field has been emerging as a domain of active clinical investigation. This article presents 4 case studies of patients with unexplained cytopenia, which hematologists may encounter in their clinical practice.