Abstract
Mast cell leukemia (MCL) is an exceedingly rare and aggressive variant of systemic mastocytosis (SM). MCL is classified as primary, occurring de novo without prior mast cell (MC) disorders or secondary, from a pre-existing SM, and acute aggressive form with C-findings that indicate organ damage or chronic indolent form without organ damage. Of the cases, 60-65% are aleukemic with < 10% circulating MCs in the peripheral blood, and the rest of the cases are leukemic with > 10% MCs. Diagnosis is typically confirmed by bone marrow biopsy revealing greater than 20% atypical or immature MCs in the smear. Specific MCL-targeted treatments are limited, and multiple treatment modalities used for SM and acute myeloid leukemia (AML) have been tried in MCL with limited success and variable survival benefit. The management has significantly advanced since the implication of the receptor tyrosine kinase type III (KIT) D816V mutation in the pathogenesis of SM and MCL. The two targeted therapies approved for MCL are midostaurin, a multikinase inhibitor, and avapritinib, a selective KIT D816V mutation-targeted tyrosine kinase inhibitor. Multiple drugs are being evaluated in clinical trials for managing MCL. MCL has a poor prognosis with a median overall survival (OS) of around 1.5 years. Further advancements and research are essential to develop treatments that may enhance median OS. In this article, we conducted a comprehensive yet simplified review of MCL, focusing primarily on its clinical manifestations and recent updates on management. We also identified the areas that require further research and emphasized the aggressive nature and poor prognosis associated with this disease.