Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven patients suffering from hypereosinophilic syndrome with clinical and/or hematological symptoms of a myeloproliferative syndrome were treated with a combination of hydroxyurea and interferon-alpha. To date, 6 of them have been followed for more than 1 year. In all cases, this therapy decreased circulating hypereosinophilia to under 1,500/mm3 and obtained normal eosinophil levels in 5 patients with a parallel regression of visceral complications. None of the patients experienced treatment-associated side effects, particularly hematological ones. Hypereosinophilic syndrome has a poor prognosis due, for the most part, to the development of visceral, cardiac and neurological complications, and, more secondarily, to the risk of progression towards acute leukemia. Conventional treatments, corticosteroids and hydroxyurea, have greatly improved the prognosis, but failure of these therapeutics remains common in the myeloproliferative form of the disease. Because interferon-alpha was proven to effectively treat chronic myeloid leukemia, it has been proposed for the treatment of hypereosinophilic syndromes, and encouraging results have been obtained despite the high daily doses required to control the disease. In the future, its association with hydroxyurea could represent an alternative therapy capable of controlling the disease at low doses thereby limiting the risk of side effects.
 ...
PMID:[Treatment of hypereosinophilic syndromes of myeloproliferative expression with the combination of hydroxyurea and interferon alpha. Apropos of 7 cases]. 836 16

Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders characterized by peripheral blood and tissue eosinophilia leading to end-organ damage. Hypereosinophilic syndrome can be fatal, particularly in patients with endomyocardial fibrosis, and treatment has traditionally been palliative or preventive. The disease shares features with myeloproliferative disorders, such as chronic myeloid leukemia, including responsiveness to hydroxyurea and interferon. The tyrosine kinase inhibitor imatinib, a highly effective treatment for chronic myeloid leukemia, has shown efficacy in normalizing eosinophil counts and resolving signs and symptoms in some HES patients. Fusion of the Fip1-like 1 gene (FIP1L1) and the platelet-derived growth factor receptor alpha gene (PDGFRA) was discovered in the majority of patients with imatinib-sensitive HES, and all patients with the fusion responded to imatinib. The product of this fusion gene, FIP1L1-PDGFRalpha, is a constitutively active protein-tyrosine kinase capable of transforming hematopoietic cells. The efficacy of relatively low imatinib concentrations in HES, mediated by inhibition of FIP1L1-PDGFRalpha kinase activity, causally implicates FIP1L1-PDGFRA in the pathogenesis in certain HES patients.
 ...
PMID:Platelet-derived growth factor receptor inhibition to treat idiopathic hypereosinophilic syndrome. 1517 99

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 alpha (FIP1L1-PDGFRA(+)) systemic mastocytosis, platelet-derived growth factor receptor beta (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 > or =1.5 x 10(9)/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-alpha 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.
 ...
PMID:Modern diagnosis and treatment of primary eosinophilia. 1599 25

Acquired eosinophilia is operationally categorized into secondary, clonal, and idiopathic types. Causes of secondary eosinophilia include parasite infections, allergic or vasculitis conditions, drugs, and lymphoma. Clonal eosinophilia is distinguished from idiopathic eosinophilia by the presence of histologic, cytogenetic, or molecular evidence of an underlying myeloid malignancy. The World Health Organization classification system for hematologic malignancies recognizes 2 distinct subcategories of clonal eosinophilia: chronic eosinophilic leukemia, not otherwise specified and myeloid/lymphoid neoplasms with eosinophilia and mutations involving platelet-derived growth factor receptor alpha/beta or fibroblast growth factor receptor 1. Clonal eosinophilia might also accompany other World Health Organization-defined myeloid malignancies, including chronic myelogenous leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and systemic mastocytosis. Hypereosinophilic syndrome, a subcategory of idiopathic eosinophilia, is defined by the presence of a peripheral blood eosinophil count of 1.5 x 10(9)/L or greater for at least 6 months (a shorter duration is acceptable in the presence of symptoms that require eosinophil-lowering therapy), exclusion of both secondary and clonal eosinophilia, evidence of organ involvement, and absence of phenotypically abnormal and/or clonal T lymphocytes. The presence of the latter defines lymphocytic variant hyper eosinophilia, which is best classified under secondary eosinophilia. In the current review, we provide a simplified algorithm for distinguishing the various causes of clonal and idiopathic eosinophilia and discuss current therapy, including new drugs (imatinib mesylate, alemtuzumab, and mepolizumab).
 ...
PMID:Hypereosinophilic syndrome and clonal eosinophilia: point-of-care diagnostic algorithm and treatment update. 2005 13

Hypereosinophilic syndrome (HES) and the association of hypereosinophilia with acute lymphoblastic leukaemia (ALL) are both rare in children. Some acute myelogenous leukaemias can present with eosinophilia, but the relationship between HES and ALL is not well known and is rarer than the relationship between HES and acute myelogenous leukaemia. Patients are diagnosed with HES when no cause is found to explain the eosinophilia leading to end organ damage. For this reason, it is recommended that patients presenting with hypereosinophilia be carefully assessed to exclude any malignant clonal proliferation. HES may present with severe clinical manifestations such as high leucocyte count, anaemia, thrombocytopaenia, hepatosplenomegaly or cardiac and neurological involvement, all of which are primarily features of myeloproliferative disorders. Some patients with HES can develop chronic eosinophilic leukaemia. Successful treatment of HES with agents used in chronic myeloid leukaemia supports the idea that HES can be a chronic myeloid disorder. There are few cases reporting an association between ALL and hypereosinophilia that precedes or is concomitant with ALL. Here we report the case of a 14-year-old girl who developed common B ALL 7 months after diagnosis and treatment of HES. Interestingly, eosinophilia was not concomitant with the diagnosis of ALL.
 ...
PMID:Does hypereosinophilic syndrome precede common B acute lymphoblastic leukaemia in childhood? A case report. 2215 91