Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders
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), 3391-3397. (doi:10.1182/blood-2002-10-3103).
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Description/Abstract
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.
| Item Type: | Article |
|---|---|
| Additional Information: | clinical observations, interventions and therapeutic trials |
| ISSNs: | 0006-4971 (print) |
| Related URLs: | |
| Subjects: | R Medicine > RB Pathology R Medicine > RC Internal medicine Q Science > QH Natural history > QH426 Genetics |
| Divisions: | University Structure - Pre August 2011 > School of Medicine > Human Genetics |
| Item ID: | 24893 |
| Date Deposited: | 04 Apr 2006 |
| Last Modified: | 01 Jun 2011 06:24 |
| Contributors: | Pardanani, Animesh (Author) Reeder, Terra (Author) Porrata, Luis F. (Author) Li, Chin-Yang (Author) Tazelaar, Henry D. (Author) Baxter, E. Joanna (Author) Witzig, Thomas E. (Author) Cross, Nicholas C.P. (Author) Tefferi, Ayalew (Author) |
| Date: | 2003 |
| Additional Information: | clinical observations, interventions and therapeutic trials |
| Status: | Published |
| Contact Email Address: | ncpc@soton.ac.uk |
| URI: | http://eprints.soton.ac.uk/id/eprint/24893 |
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