title: Successful treatment of a chronic-phase T-315I-mutated chronic myelogenous leukemia patient with a combination of imatinib and interferon-alfa.
abstract: The T315I BCR-ABL mutation in chronic myelogenous leukemia (CML) patients is responsible for up to 20% of all clinically observed resistance. This mutation confers resistance not only to imatinib, but also to second-generation BCR-ABL tyrosine kinases, such as nilotinib and dasatinib. A number of strategies have been implemented to overcome this resistance, but allogeneic stem cell transplantation remains the only established therapeutic option for a cure. A 61-year-old male was diagnosed with Philadelphia chromosome-positive chronic-phase CML in 2002. He was initially treated with imatinib and complete cytogenetic response (CCyR) was achieved 12 months later. However, after 18 months, a loss of CCyR was observed and a molecular study at 24 months revealed a T315I mutation of the BCR-ABL gene. At 30 months, imatinib/interferon-alfa (IFNα) combination therapy was initiated in an effort to overcome the resistance. Thirty months later, he re-achieved CCyR, and the T315I BCR-ABL mutation disappeared at 51 months. To our knowledge, this is the first case report showing the effectiveness of imatinib/IFNα combination therapy for CML patients bearing the T315I BCR-ABL mutation.
authors.affiliation: Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Itonaga
authors.forename: Hideki
authors.initials: H
authors.lastname: Tsushima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hata
authors.forename: Emi
authors.initials: E
authors.lastname: Matsuo
authors.forename: Daisuke
authors.initials: D
authors.lastname: Imanishi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Imaizumi
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Fukushima
authors.forename: Yuko
authors.initials: Y
authors.lastname: Doi
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mori
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
authors.forename: Masao
authors.initials: M
authors.lastname: Tomonaga
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyazaki
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D001549:Benzamides; D004359:Drug Therapy, Combination; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D007155:Immunologic Factors / Q000008:administration & dosage; D016898:Interferon-alpha / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D017354:Point Mutation; D011743:Pyrimidines / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007155:Immunologic Factors; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl