Response of six patients with idiopathic hypereosinophilic syndrome to interferon alfa*

Butterfield, J. H.; Gleich, Gerald J.

doi:10.1016/0091-6749(94)90348-4

Cited by 61 publications

(31 citation statements)

References 26 publications

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“…9 IFN-␣ also has been used with success in a limited number of patients. 61 Patients with cardiac involvement have undergone surgery with valve replacement and with endomyocardectomy. Patients with thrombosis have undergone thrombectomy.…”

Section: Idiopathic Hesmentioning

confidence: 99%

Beyond chronic myelogenous leukemia

Cortés¹,

Kantarjian²

2004

Cancer

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The myeloproliferative disorders (MPDs) are chronic malignant conditions originating from the clonal expansion of a multipotential hematopoietic stem cell.These diseases include polycythemia vera (PV), essential thrombocythenia, atypical chronic myeloid leukemia, idiopathic hypereosinophilic syndrome (HES), ag- Insight into the molecular pathogenesis of MPDs will improve the definitions of different disease categories and suggests that signal transduction inhibition is likely to be an increasingly important treatment option in the future.

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Section: Idiopathic Hesmentioning

confidence: 99%

Beyond chronic myelogenous leukemia

Cortés¹,

Kantarjian²

2004

Cancer

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“…However, most patients relapse during the steroid taper and often require additional drug therapy. In this regard, interferon-α is currently considered the second-line treatment of choice based on numerous reports of well-documented long-lasting remissions in the majority of treated patients [91,92,93,94,95,96,97,98,99,100,101,102,103,104]. A starting dose of interferon-α between 1 and 3 million units given subcutaneously 3 times per week is recommended and the dose can be increased or decreased depending on drug side effects as well as response [94, 100, 105].…”

Section: Hypereosinophilic Syndromementioning

confidence: 99%

Modern Diagnosis and Treatment of Primary Eosinophilia

Tefferi

2005

Acta Haematol

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The recent discovery of an eosinophilia-specific, imatinib-sensitive, karyotypically occult but fluorescence in situ hybridization-apparent molecular lesion in a subset of patients with blood eosinophilia has transformed the diagnostic as well as treatment approach to eosinophilic disorders. Primary (i.e. nonreactive) eosinophilia is considered either ‘clonal’ or ‘idiopathic’ based on the presence or absence, respectively, of either a molecular or bone marrow histological evidence for a myeloid neoplasm. Clonal eosinophilia might accompany a spectrum of clinicopathological entities, the minority of whom are molecularly characterized; Fip1-like-1-platelet-derived growth factor receptor α (FIP1L1-PDGFRA⁺) systemic mastocytosis, platelet-derived growth factor receptor β (PDGFRB)-rearranged atypical myeloproliferative disorder, chronic myeloid leukemia, and the 8p11 syndrome that is associated with fibroblast growth factor receptor 1 (FGFR1) rearrangement. Hypereosinophilic syndrome (HES) is a subcategory of idiopathic eosinophilia and is characterized by an absolute eosinophil count of ≧1.5 × 10⁹/l for at least 6 months as well as eosinophil-mediated tissue damage. At present, a working diagnosis of primary eosinophilia mandates a bone marrow examination, karyotype analysis, and additional molecular studies in order to provide the patient with accurate prognostic information as well as select appropriate therapy. For example, the presence of either PDGFRA or PDGFRB mutations warrants the use of imatinib in clonal eosinophilia. In HES, prednisone, hydroxyurea, and interferon-α constitute first-line therapy, whereas imatinib, cladribine, and monoclonal antibodies to either interleukin-5 (mepolizumab) or CD52 (alemtuzumab) are considered investigational. Allogeneic transplantation offers a viable treatment option for drug-refractory cases.

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“…138,139 Interferon-␣ (IFN-␣) can elicit long-term hematologic and cytogenetic responses in HES and CEL patients resistant to other therapies, including prednisone and hydroxyurea. 109,[140][141][142][143][144][145] Some have advocated its use as initial therapy for these diseases. 144 Remissions have been associated with improvement in clinical symptoms and organ disease, including hepatosplenomegaly, 140,144 cardiac and thromboembolic complications, 109,141 mucosal ulcers, 143 and skin involvement.…”

Section: Current Treatmentmentioning

confidence: 99%

“…109,[140][141][142][143][144][145] Some have advocated its use as initial therapy for these diseases. 144 Remissions have been associated with improvement in clinical symptoms and organ disease, including hepatosplenomegaly, 140,144 cardiac and thromboembolic complications, 109,141 mucosal ulcers, 143 and skin involvement. 145 IFN-␣ exerts pleiotropic effects including inhibition of eosinophil proliferation and differentiation.…”

Section: Current Treatmentmentioning

confidence: 99%

The FIP1L1-PDGFRα fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management

Gotlib

Cools

Malone

et al. 2004

Blood

262

205

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Idiopathic hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) comprise a spectrum of indolent to aggressive diseases characterized by unexplained, persistent hypereosinophilia. These disorders have eluded a unique molecular explanation, and therapy has primarily been oriented toward palliation of symptoms related to organ involvement. Recent reports indicate that HES and CEL are imatinib-responsive malignancies, with rapid and complete hematologic remissions observed at lower doses than used in chronic myelogenous leukemia (CML). These BCR-ABL-negative cases lack activating mutations or abnormal fusions involving other known target genes of imatinib, implicating a novel tyrosine kinase in their pathogenesis. A bedside-to-benchtop translational research effort led to the identification of a constitutively activated fusion tyrosine kinase on chromosome 4q12, derived from an interstitial deletion, that fuses the platelet-derived growth factor receptor-␣ gene (PDGFRA) to an uncharacterized human gene FIP1-like-1 (FIP1L1). However, not all HES and CEL patients respond to imatinib, suggesting disease heterogeneity. Furthermore, approximately 40% of responding patients lack the FIP1L1-PDGFRA fusion, suggesting genetic heterogeneity. This review examines the current state of knowledge of HES and CEL and the implications of the FIP1L1-PDGFRA discovery on their diagnosis, classification, and management. IntroductionProtean biologic and clinical presentations characterize idiopathic hypereosinophilia (HES). HES is similar to other diseases given the moniker "diagnosis of exclusion," in that limited understanding of the pathogenesis of the disease has hampered therapeutic advances. The demonstration of increased myeloblasts or clonality or the development of either granulocytic sarcoma or acute myeloid leukemia helps clarify the origin of some cases of chronic eosinophilic leukemia. 1 In a subset of patients, hypereosinophilia is related to excessive secretion of eosinophilopoietic cytokines from a clonal population of lymphocytes. 2 The identification of FIP1-like-1-platelet-derived growth factor receptor-␣ (FIP1L1-PDGFRA) in cases of HES/CEL adds to a growing list of activated fusion tyrosine kinases linked to the pathogenesis of chronic myeloproliferative disorders. 3 It is unique, however, because it is the first description of a gain-of-function fusion protein resulting from a cryptic interstitial deletion between genes rather than a reciprocal chromosomal translocation. The FIP1L1-PDGFR␣ fusion protein transforms hematopoietic cells, and its kinase activity is inhibited by imatinib at a cellular 50% inhibitory concentration (IC 50 ) 100-fold lower than BCR-ABL. 3 Acquisition of an imatinib resistance mutation in the adenosine triphosphate (ATP)-binding domain of PDGFRA in a relapsed patient previously responsive to imatinib supports a critical role for FIP1L1-PDGFR␣ in the pathogenesis of disease and demonstrates that FIP1L1-PDGFR␣ is the therapeutic target of imatinib. 3 The identification of t...

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Response of six patients with idiopathic hypereosinophilic syndrome to interferon alfa*

Cited by 61 publications

References 26 publications

Beyond chronic myelogenous leukemia

Beyond chronic myelogenous leukemia

Modern Diagnosis and Treatment of Primary Eosinophilia

The FIP1L1-PDGFRα fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management

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