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Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders

Record type: Article

Imatinib mesylate (Gleevec), a small molecule inhibitor of abl, kit, and platelet-derived growth factor receptor (PDGFR) tyrosine kinases, has been reported to be effective in the treatment of hypereosinophilic syndrome (HES) and a rare eosinophilia-associated chronic myeloid disorder (eos-CMD) characterized by the t(5;12)(q33;p13) cytogenetic abnormality. In the current study, we sought to confirm the preliminary observations in HES as well as evaluate the therapeutic value of imatinib in eos-CMD that is not associated with t(5;12)(q33;p13). Five patients with HES (all men, median age = 46 years) and 2 with eos-CMD (both men, aged 45 and 58 years) were treated with imatinib at a starting dose of 100 to 400 mg/day. Cytogenetic studies showed no evidence of either the bcr-abl translocation or t(5;12)(q33;p13) in any patient. Screening of exons encoding the intracellular catalytic domains and extracellular ligand binding domains of PDGFR (exons 2-23) and c-kit (exons 1-21) in 6 patients demonstrated mostly previously known polymorphisms. At a median follow-up of 17 weeks (range, 10-33 weeks), 2 patients with HES and 1 with eos-CMD have achieved complete clinical remission and 1 additional patient with HES has achieved a partial remission. In contrast to previous observations, all 4 responding patients had elevated serum interleukin-5 levels. Although the drug was well tolerated in most patients, a previously unrecognized treatment toxicity of acute left ventricular dysfunction occurred in a responding patient with HES within the first week of treatment. Myocardial biopsy revealed eosinophilic infiltration and degranulation, and the cardiogenic shock was reversed with the prompt institution of corticosteroid therapy.

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Citation

Pardanani, Animesh, Reeder, Terra, Porrata, Luis F., Li, Chin-Yang, Tazelaar, Henry D., Baxter, E. Joanna, Witzig, Thomas E., Cross, Nicholas C.P. and Tefferi, Ayalew (2003) Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders Blood, 101, (9), pp. 3391-3397. (doi:10.1182/blood-2002-10-3103).

More information

Published date: 2003
Additional Information: clinical observations, interventions and therapeutic trials

Identifiers

Local EPrints ID: 24893
URI: http://eprints.soton.ac.uk/id/eprint/24893
ISSN: 0006-4971
PURE UUID: 598a0d1a-687f-41f4-a86d-7f3a70b8f039
ORCID for Nicholas C.P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

Catalogue record

Date deposited: 04 Apr 2006
Last modified: 17 Jul 2017 16:12

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Contributors

Author: Animesh Pardanani
Author: Terra Reeder
Author: Luis F. Porrata
Author: Chin-Yang Li
Author: Henry D. Tazelaar
Author: E. Joanna Baxter
Author: Thomas E. Witzig
Author: Ayalew Tefferi

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