The term
hypereosinophilic syndrome (HES) was initially introduced to describe a group of diseases all characterized by persistent unexplained
hypereosinophilia. Additional names have subsequently been introduced to describe specific variants of HES, such as the myeloid variant and the lymphoid variant, or to indicate idiopathic HES, for which the cause of the
eosinophilia is completely unknown. Molecular analysis led to the identification of the clonal origin of several subgroups of HES, clearly establishing these diseases as true
leukemias. These cases of
hypereosinophilia are now referred to as 'myeloid
neoplasms associated with
eosinophilia and abnormalities of
PDGF receptor A and B (PDGFRA and
PDGFRB), or
FGF receptor 1 (FGFR1)'. In cases for which clonality is clear, but no PDGFRA,
PDGFRB or FGFR1 rearrangement could be demonstrated, the term '
chronic eosinophilic leukemia, not otherwise specified' is preferred. Most importantly, patients with rearrangements of PDGFRA or
PDGFRB can be efficiently treated with the
kinase inhibitor
imatinib. Additional potent
kinase inhibitors have been identified, also including inhibitors that target FGFR1 and
imatinib-resistant variants of
PDGFRalpha. For treatment of unexplained
hypereosinophilia and '
chronic eosinophilic leukemia, not otherwise specified; different therapeutic strategies are currently under investigation and promising results have been obtained using humanized anti-IL-5
antibodies. Further molecular understanding of the cause of these 'idiopathic' diseases may lead to the development of novel targeted
therapies.