INCLUSION CRITERIA:
All subjects must meet the established diagnostic criteria for idiopathic hypereosinophilic syndrome: eosinophilia greater than 1,500/mm3 on two occasions at least 6 months apart, no known etiology for the eosinophilia despite careful clinical evaluation, and evidence of end organ damage (histologic evidence of tissue infiltration by eosinophils and/or objective evidence of clinical pathology in any organ system that is temporally associated with eosinophilia and not clearly attributable to another cause).
All subjects must fit one of the following three categories:
(a) refractory to or intolerant of steroids, interferon alpha and hydroxyurea
(b) presence of FIP1L1/PDGFRA or bcr-abl detected by RT-PCR
(c) presence of greater than or equal to 4 of the following laboratory criteria suggestive of a myeloproliferative disorder:
i. dysplastic eosinophils on peripheral smear
ii. serum B12 level greater than or equal to 1000 pg/ml
iii. serum tryptase level greater than or equal to 12
iv. anemia and/or thrombocytopenia
v. bone marrow cellularity greater than 80% with left shift in maturation
vi. dysplastic (spindle-shaped) mast cells on bone marrow biopsy
vii. evidence of fibrosis on bone marrow biopsy
viii. dysplastic megakaryocytes on bone marrow biopsy
All subjects must be at least 2 years of age.
Negative serum beta-hCG within 24 hours prior to drug administration for women of childbearing potential to exclude early pregnancy.
All subjects (men and women) must agree to practice abstinence or effective contraception during administration of imatinib mesylate and for 6 months after discontinuation of drug.
Of note, failure of the standard chemotherapeutic agents (steroids, hydroxyurea, and interferon alpha) will not be a prerequisite for participation in this protocol for the following reasons. 1) There is no approved therapy for HES. 2) Steroid therapy in the myeloproliferative subset of HES patients is generally ineffective. 3) Although hydroxyurea and interferon alpha are initially effective in most cases, a majority of patients become refractory to or intolerant of these agents within a relatively short period of time (less than 1 year). 4) Data from other myeloproliferative disorders, including CML, suggest that interferon and imatinib mesylate, but not hydroxyurea, are associated with cytogenetic remission. 5) The reported incidence and severity of side effects from imatinib mesylate in patients with CML appears comparable to (or less than) those associated with interferon alpha.
Although a private physician is not required for inclusion in the study, it is strongly recommended that all subjects have a physician outside the NIH for routine medical care and emergencies.
EXCLUSION CRITERIA:
Pregnancy or nursing women
HIV positivity or other known immunodeficiency
Systemic mastocytosis
Absolute neutrophil count less than 1000/mm3 or platelet count less than 10, 000/mm3 or less than 50,000/m3 with clinical evidence of bleeding.
Elevated transaminases (greater than 5 times the upper limit of normal) or elevated bilirubin (greater than 3 times the upper limit of normal)
Any condition that, in the investigator's opinion, places the patient at undue risk by participating in the study