title: A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction.
abstract: Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935).
authors.affiliation: Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Naoto
authors.initials: N
authors.lastname: Takahashi
authors.forename: Kaichi
authors.initials: K
authors.lastname: Nishiwaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
authors.forename: Makoto
authors.initials: M
authors.lastname: Kashimura
authors.forename: Hisashi
authors.initials: H
authors.lastname: Wakita
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hatano
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Itoh
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Masuoka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Aotsuka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Sinobu
authors.initials: S
authors.lastname: Takahara
authors.forename: Koji
authors.initials: K
authors.lastname: Sano
authors.forename: Jun
authors.initials: J
authors.lastname: Kuroki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hata
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.forename: Atsuko
authors.initials: A
authors.lastname: Mugitani
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakane
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sawada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D038622:Internationality; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000097:blood / Q000627:therapeutic use*; D011743:Pyrimidines / Q000097:blood / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods / Q000592:standards*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate