title: [Successful treatment with low-dose dasatinib in a patient with chronic eosinophilic leukemia intolerant to imatinib].
abstract: A 77-year-old man with cough and dyspnea was admitted to hospital. Chest X-ray demonstrated reticulated shadows in the bilateral inferior lung fields and marked eosinophilia was detected in peripheral blood. Although he received steroid pulse therapy, eosinophilia became more serious and he was referred to our hospital. Bone marrow examination demonstrated a hypercellular marrow that consisted predominantly of dysplastic eosinophils with differentiation. FISH analysis of bone marrow cells demonstrated 4q12 deletion and RT-PCR analysis detected FIP1L1-PDGFRA fusion gene, leading to the diagnosis of chronic eosinophilic leukemia (CEL). Treatment with low-dose imatinib was immediately initiated; however, drug-induced systemic edema was progressive and became intolerable. Therefore, we changed imatinib to low-dose dasatinib (20 mg/day), resulting in complete molecular response of CEL after 3 months without any severe adverse effects. This is the first report on the efficacy of low-dose dasatinib for the treatment of CEL. The peak level (Cmax) of dasatinib in this patient was 55.3 nM, which exceeded the concentration of dasatinib required to inhibit cells with FIP1L1-PDGFRA by 50%. Thus, low-dose dasatinib with therapeutic drug monitoring can be a useful therapy for imatinib-intolerant CEL even in elderly patients.
authors.affiliation: Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University.
authors.forename: Jun
authors.initials: J
authors.lastname: Imagawa
authors.forename: Yuka
authors.initials: Y
authors.lastname: Harada
authors.forename: Tetsumi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Miho
authors.initials: M
authors.lastname: Tarutani
authors.forename: Akiro
authors.initials: A
authors.lastname: Kimura
authors.forename: Kana
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Morita
authors.forename: Hironori
authors.initials: H
authors.lastname: Harada
mesh_terms: D000368:Aged; D001549:Benzamides; D002908:Chronic Disease; D000069439:Dasatinib; D016903:Drug Monitoring; D004361:Drug Tolerance; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000235:genetics; D000068877:Imatinib Mesylate; D008297:Male; D058990:Molecular Targeted Therapy; D010879:Piperazines; D011743:Pyrimidines / Q000008:administration & dosage* / Q000097:blood; D020796:Receptor, Platelet-Derived Growth Factor alpha; D012074:Remission Induction; D013844:Thiazoles / Q000008:administration & dosage* / Q000097:blood; D016896:Treatment Outcome; D039221:mRNA Cleavage and Polyadenylation Factors
chemical_list: D001549:Benzamides; C479818:FIP1L1 protein, human; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D039221:mRNA Cleavage and Polyadenylation Factors; D000068877:Imatinib Mesylate; D020796:Receptor, Platelet-Derived Growth Factor alpha; D000069439:Dasatinib