TY - JOUR
T1 - A critical appraisal of conventional and investigational drug therapy in patients with hypereosinophilic syndrome and clonal eosinophilia
AU - Kalac, Matko
AU - Quintás-Cardama, Alfonso
AU - Vrhovac, Radovan
AU - Kantarjian, Hagop
AU - Verstovsek, Srdan
PY - 2007/9/1
Y1 - 2007/9/1
N2 - 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 α (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.
AB - 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 α (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.
KW - Alemtuzumab
KW - Eosinophilia
KW - Hypereosinophilic syndrome
KW - Imatinib
KW - Mepolizumab
KW - Tyrosine kinase inhibitors
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U2 - 10.1002/cncr.22920
DO - 10.1002/cncr.22920
M3 - Review article
C2 - 17654661
AN - SCOPUS:34548177003
SN - 0008-543X
VL - 110
SP - 955
EP - 964
JO - Cancer
JF - Cancer
IS - 5
ER -