Sakurai Masatoshi, Kikuchi Taku, Karigane Daiki, Kasahara Hidenori, Matsuki Eri, Hashida Risa, Yamane Yusuke, Abe Ryohei, Koda Yuya, Toyama Takaaki, Kato Jun, Shimizu Takayuki, Yokoyama Yuta, Suzuki Sayo, Nakamura Tomonori, Okamoto Shinichiro, Mori Takehiko
Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Division of Pharmaceutical Care Sciences, Keio University Faculty of Pharmacy, Tokyo, Japan.
Int J Hematol. 2019 Mar;109(3):292-298. doi: 10.1007/s12185-019-02596-z. Epub 2019 Jan 24.
Knowledge of the toxicity profile of long-term treatment with imatinib is limited. In the present study, we sought to evaluate renal function and hemoglobin levels during long-term imatinib treatment. Eighty-two patients with chronic myelogenous leukemia in chronic phase who had been on imatinib for over 5 years were retrospectively analyzed. The mean estimated glomerular filtration rate (eGFR) was significantly decreased over 5 years (77 ± 17 to 62 ± 14 ml/min/1.73m², P < 0.001). Higher age and lower eGFR value at initiation of imatinib were significantly associated with development of renal dysfunction by multivariate analyses. Mean hemoglobin levels also significantly decreased over the 5-year period (12.9 ± 1.7 to 12.4 ± 1.3 g/dl, P < 0.01). The rate of decrease in eGFR correlated significantly with hemoglobin levels (correlation coefficient = - 0.249, P < 0.05). Serum erythropoietin (EPO) levels did not increase in 16 patients with both renal dysfunction and anemia (median, 31.9 mIU/ml). In patients who participated in a clinical trial of imatinib discontinuation, mean eGFR (50.0 ± 6.5 to 56.0 ± 10.2 ml/min/1.73m², P < 0.05) and hemoglobin levels (12.0 ± 1.7 to 14.0 ± 1.6 g/dl, P < 0.01) improved significantly at 1 year after discontinuation. These findings suggest that long-term imatinib results in a partially reversible continuous decline in renal function and decreased hemoglobin levels.
伊马替尼长期治疗的毒性特征方面的知识有限。在本研究中,我们试图评估伊马替尼长期治疗期间的肾功能和血红蛋白水平。对82例慢性期慢性髓性白血病患者进行了回顾性分析,这些患者接受伊马替尼治疗超过5年。平均估计肾小球滤过率(eGFR)在5年期间显著下降(从77±17降至62±14ml/min/1.73m²,P<0.001)。多因素分析显示,较高的年龄和伊马替尼治疗开始时较低的eGFR值与肾功能障碍的发生显著相关。平均血红蛋白水平在5年期间也显著下降(从12.9±1.7降至12.4±1.3g/dl,P<0.01)。eGFR的下降速率与血红蛋白水平显著相关(相关系数=-0.249,P<0.05)。16例同时患有肾功能障碍和贫血的患者血清促红细胞生成素(EPO)水平未升高(中位数为31.9mIU/ml)。在参与伊马替尼停药临床试验的患者中,停药1年后平均eGFR(从50.0±6.5升至56.0±10.2ml/min/1.73m²,P<0.05)和血红蛋白水平(从12.0±1.7升至14.0±1.6g/dl,P<0.01)显著改善。这些发现表明,伊马替尼长期治疗会导致肾功能部分可逆的持续下降以及血红蛋白水平降低。