Imatinib therapy in clonal eosinophilic disorders, including systemic mastocytosis

Primary (nonreactive) eosinophilia is operationally classified as either a "clonal" or an "idiopathic" process. Clonal eosinophilia stipulates the presence of cytogenetic, molecular, or bone marrow histologic evidence of acute leukemia or a chronic myeloid disorder. Idiopathic eosinophilia is a diagnosis of exclusion that is made after ruling out both "secondary" (reactive) and clonal eosinophilia. Hypereosinophilic syndrome is a subclass of idiopathic eosinophilia that requires the documentation of both sustained eosinophilia (≥1500/μL for at least 6 months) and target-organ damage. A series of novel observations in the last 5 years have warranted a refined approach to the diagnosis as well as the treatment of clonal eosinophilic disorders, including systemic mastocytosis. At the center of these new developments are mutations involving the platelet-derived growth factor receptor genes (PDGFRA and PDGFRB), which have been pathogenetically linked to clonal eosinophilia, and their presence predicts complete as well as durable treatment responses to imatinib mesylate. The bone marrow histologic phenotype of these imatinib-sensitive eosinophilic disorders includes systemic mastocytosis, chronic eosinophilic leukemia, chronic myelomonocytic leukemia, and atypical chronic myeloproliferative disorder.