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

作者：Shinohara Yoshinori; Takahashi Naoto^*; Nishiwaki Kaichi; Hino Masayuki; Kashimura Makoto; Wakita Hisashi; Hatano Yoshiaki; Hirasawa Akira; Nakagawa Yasuaki; Itoh Kuniaki; Masuoka Hidekazu; Aotsuka Nobuyuki; Matsuura Yasuhiro; Takahara Sinobu; Sano Koji; Kuroki Jun; Hata Tomoko; Nakamae Hirohisa; Mugitani Atsuko; Nakane Takahiko; Miyazaki Yasushi; Niioka Takenori; Miura Masatomo; Sawada Kenichi

来源：Haematologica-The Hematology Journal, 2013, 98(9): 1407-1413.

DOI：10.3324/haematol.2013.085167

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-Abelsonl 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%26gt;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, UMIN0000004935).

• 出版日期2013-9