Renal dysfunction and anemia associated with long-term imatinib treatment in patients with chronic myelogenous leukemia.
Renal dysfunction and anemia associated with long-term imatinib treatment in patients with chronic myelogenous leukemia.
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慢性粒细胞白血病患者长期伊马替尼治疗相关的肾功能障碍和贫血。
DOI：
10.1007/s12185-019-02596-z
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
and Mori Ta
中科院分区：
文献类型：
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作者：
Sakurai Masatoshi;Karigane Daiki;Kasahara Hidenori;Matsuki Eri;Hashida Risa;Yamane Yusuke;Abe Ryohei;Koda Yuya;Toyama Takaaki;Kikuchi Taku;Kato Jun;Shimizu Takayuki;Yokoyama Yuta;Suzuki Sayo;Nakamura Tomonori;Okamoto Shinichiro;and Mori Ta
对伊马替尼长期治疗的毒性特征的了解有限。在本研究中，我们试图评估长期伊马替尼治疗期间的肾功能和血红蛋白水平。回顾性分析82例服用伊马替尼5年以上的慢性粒细胞白血病慢性期患者。平均估计肾小球滤过率（eGFR）在 5 年内显着下降（77±17 至 62±14 ml/min/1.73m2，P<0.001）。多变量分析显示，开始使用伊马替尼时年龄较大和 eGFR 值较低与肾功能障碍的发生显着相关。平均血红蛋白水平在 5 年期间也显着下降（12.9±1.7 至 12.4±1.3 g/dl，P<0.01）。 eGFR下降率与血红蛋白水平显着相关（相关系数=−0.249，P< 0.05）。 16 名同时患有肾功能不全和贫血的患者的血清促红细胞生成素 (EPO) 水平没有增加（中位数为 31.9 mIU/ml）。在参加伊马替尼停药临床试验的患者中，平均 eGFR（50.0±±6.5 至 56.0±10.2 ml/min/1.73m²，P<±0.05）和血红蛋白水平（12.0±±1.7 至14.0 ± 1.6 g/dl，P< 0.01）在停药后 1 年显着改善。这些发现表明，长期服用伊马替尼会导致肾功能部分可逆的持续下降和血红蛋白水平下降。
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.