Chronic eosinophilic leukaemia-Not otherwise specified: Clinical features, genomic insight and therapeutic strategies.

Abstract

Chronic eosinophilia leukaemia-not otherwise specified (CEL-NOS) is a rare myeloproliferative neoplasm characterized by persistent clonal hypereosinophilia. Recent advances in genetics have refined diagnostic criteria, leading to the identification of CEL subtypes with specific cytogenetic and molecular abnormalities now classified as myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, which may benefit from targeted therapies. In contrast, CEL-NOS lacks specific genetic drivers and intervention points to halt leukemogenesis. Molecular techniques have also enabled the definition of clonality in a considerable percentage of cases otherwise classified as idiopathic hypereosinophilic syndrome. CEL-NOS poses a significant therapeutic challenge due to limited treatment options, poor prognosis and the risk of progression to acute leukaemia. Patients, often elderly and with comorbidities, face restricted access to transplantation, the only potentially curative treatment. Unfortunately, the prognosis remains poor even post-transplant, with a 5-year survival rate of only one-third of patients. Other therapies, including steroids, cytoreductive and immunomodulatory treatments, offer limited and temporary responses with significant side effects. This review aims to consolidate current knowledge on CEL-NOS, covering diagnostic approaches, genetic advancements and therapeutic challenges. It seeks to provide a comprehensive overview and highlight critical areas for future research.