Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome

Abstract

We recently described a subset of patients with a myeloproliferative variant of hypereosinophilic syndrome (MHES) characterized by elevated serum tryptase levels, increased atypical mast cells in the bone marrow, tissue fibrosis, and the presence of the fusion tyrosine kinase, FIP1L1-PDGFR␣, which is a therapeutic target of imatinib mesylate. Seven patients with MHES were treated with imatinib mesylate (300-400 mg daily). Clinical improvement and resolution of eosinophilia was observed in all patients, although cardiac dysfunction, when present, was not altered by therapy. Reversal of bone marrow pathology, including increased cellularity, the presence of spindle-shaped mast cells, and myelofibrosis, was evident in all patients at 4 to 8 weeks following initiation of therapy. This was accompanied by a decrease in activated eosinophils and mast cells in the peripheral blood and bone marrow, respectively. Serum tryptase levels declined rapidly to normal levels in all patients and remained in the normal range throughout therapy. Molecular remission, with disappearance of detectable FIP1L1/ PDGFRA (F/P) transcripts, was achieved in 5 of 6 patients tested. The lack of reversal of cardiac abnormalities and persistence of the F/P mutation in some patients suggests that early intervention with higher doses of imatinib mesylate may be desirable in the treatment of patients with MHES. (Blood. 2004;103: 473-478)

Gastrointestinal Eosinophilia

“…Recently, these patients have been shown to meet minor criteria for systemic mastocytosis, having elevated levels of serum mast cell tryptase, and high numbers of dysplastic mast cells in the bone marrow. [72,73] These patients go on to develop eosinophilic endomyocardial disease with embolization to peripheral organs including the extremities and the brain, and they strikingly resemble the patients originally designated by Hardy and Anderson. [61] However, it appears that any disease that results in prolonged and marked eosinophilia can be associated with endomyocardial disease.…”

Imatinib mesylate therapy reduces bone marrow fibrosis in patients with chronic myelogenous leukemia

“…Similar reductions in fibrosis were observed with imatinib therapy in patients with the myeloproliferative variant of hypereosinophilic syndrome. 17 …”

Clinical Features and Outcomes of Eosinophilic Myocarditis Patients Treated with Prednisolone at a Single Institution Over a 27-Year Period

“…The limited available literature of < 30 published case reports suggests that treatment with PSL may be effective because of the immunological pathogenesis of eosinophilic myocarditis (5-22) ( Table 5). In the four reported case series, which included 3 cases, 5 cases, 3 cases and 3 cases, respectively (5,9,16,17), the majority of eosinophilic myocarditis patients were initially treated with PSL at a dose of 1 mg/kg/day (Table 5). Thereafter, a maintenance dose of PSL was administered or the drug was discontinued (Table 5).…”

“…This immunological pathogenesis and the results of a number of earlier reports (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23), suggest that immunosuppression with prednisolone (PSL) may be a potentially useful approach to treat eosinophilic myocarditis. Here we describe the clinical features and outcomes of eosinophilic myocarditis in 7 patients treated at our institution.…”

“…Moreover, Mason et al reported that immunosuppressive therapy does not improve left ventricular function or outcome in patients with myocarditis (4). Because there are only a limited number of published reports on eosinophilic myocarditis (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), its clinical features and prognosis remain unclear.…”