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).

Download

Full text not available from this repository.

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
ePrint ID: 24893
Date Deposited: 04 Apr 2006
Last Modified: 27 Mar 2014 18:13
URI: http://eprints.soton.ac.uk/id/eprint/24893

Actions (login required)

View Item View Item