title: A critical appraisal of conventional and investigational drug therapy in patients with hypereosinophilic syndrome and clonal eosinophilia.
abstract: Hypereosinophilic syndrome (HES) is a rare disorder characterized by persistent and marked eosinophilia, leading to end-organ damage. Over the last decade, great progress has been made in unraveling the molecular basis of HES that has resulted in the characterization of specific genetic alterations linked to clonal eosinophilia. The most frequently encountered genetic aberrancy is the cryptic FIP1-like 1/platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) fusion transcript, which results in an eosinophilic, myeloproliferative disorder. In addition, in a subset of patients with HES, a population of aberrant T cells that secretes interleukin-5 can be identified, indicating the existence of lymphocyte-mediated hypereosinophilia. These new insights have led to both a genetically based (re)classification of eosinophilic blood disorders and to effective therapies with targeted agents, such as small-molecule tyrosine kinase inhibitors (eg, imatinib, nilotinib, PKC412) and, more recently, monoclonal antibodies (eg, mepolizumab, alemtuzumab). These targeted therapies hold great promise for improving the clinical outcomes of patients with HES and clonal eosinophilia, and they have exhibited relatively safe toxicity profiles.
authors.affiliation: Department of Medicine, University Hospital Merkur, Zagreb, Croatia.
authors.forename: Matko
authors.initials: M
authors.lastname: Kalac
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: Radovan
authors.initials: R
authors.lastname: Vrhovac
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D001549:Benzamides; D002999:Clone Cells / Q000473:pathology; D004802:Eosinophilia / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000473:pathology; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000074323:Alemtuzumab; D000068877:Imatinib Mesylate; C434107:mepolizumab; C498826:nilotinib