Imatinib therapy for hypereosinophilic syndrome and other eosinophilic disorders.
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 beta (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.
Pardanani
Animesh
A
Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Reeder
Terra
T
Porrata
Luis F
LF
Li
Chin-Yang
CY
Tazelaar
Henry D
HD
Baxter
E Joanna
EJ
Witzig
Thomas E
TE
Cross
Nicholas C P
NC
Tefferi
Ayalew
A
D000328:Adult; D001549:Benzamides; D004341:Drug Evaluation; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000145:classification / Q000188:drug therapy* / Q000235:genetics; D000068877:Imatinib Mesylate; D015848:Interleukin-5 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics; D012074:Remission Induction; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced
D001549:Benzamides; D004791:Enzyme Inhibitors; D015848:Interleukin-5; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020797:Receptor, Platelet-Derived Growth Factor beta