口服甲磺酸伊马替尼对粒细胞性白血病患者精液质量的影响

Impairment of spermatoza in male patients with chronic myelogenous leukemia treated with oral Imatinib Mesylate

目的探讨口服甲磺酸伊马替尼对精液质量的影响，研究其生殖毒性。方法研究对象共37例，分为两组。（1）白血病组：14例慢性粒细胞白血病（CML）男性患者，平均年龄（34．00±11．40）岁，口服甲磺酸伊马替尼治疗CML，400mg／d，用药时间为3个月。（2）正常对照组：23例正常生育能力男性，平均年龄（30．78±5．98）岁。所有研究对象均进行精液常规分析；采用抗活性半胱氨酸蛋白酶3（Caspase-3）标记法使用流式细胞仪进行精子细胞凋亡率分析。测得的数据进行统计学分析。结果CML组服用甲磺酸伊马替尼治疗前、后精液质量及精子细胞凋亡率差异均具有统计学意义。治疗前、后精子密度分别为（113．47±37．40）10。／ml及（34．32±21．46）106／ml（P〈0．01）；精子活动率分别为（72．21±16．52）％及（41．21±18．96）％（P〈0．01），精子活力（a＋b％）分别为（63．40±16．67）％及（34．22±19．10）％（P〈0．01）；畸形率分别为（70．64±9．35）％及（80．93±9．87）％（P〈0．01）；治疗前、后精子细胞凋亡率分别为（0．19±0．09）％及（2．52±0．38）％（P〈0．01）。CML组治疗后精液质量及精子细胞凋亡率与正常对照组比较，差异均有统计学意义（P〈0．01）。精子细胞凋亡率与精液分析各参数之间有显著相关关系（P〈0．01）。结论口服甲磺酸伊马替尼可导致精液质量下降，精子细胞凋亡率增加。提示用药前、后应监测精液质量，及时冷冻保存精液，从而保存患有CML的男性生育力。

Objective To investigate the effect of oral Imatinib Mesylate on the quality of the semen of male patients with chronic myelogenous leukemia and explore its reproductive toxicity. Methods Thirty-seven semen samples were collected, of which 23 were from healthy men, averagely aged 30.78±5.98 （normal control group） and 14 from male patients, averagely aged 34.00±11.40 with chronic myelogenous leukemia treated with oral Imatinib Mesylate, 400mg/d （ experimental group） for three months. Semen routine analysis was performed according to the WHO semen analysis manual. A Spermetoza was first labeled with cysteine proteinase 3 （Caspase-3）, and then sperm apoptosis rate was analyzed by a flow cytometer. The data was statistically analyzed. Results The average sperm density, motility, motility a＋b%, abnormal sperm rate, sperm apoptosis rate of the experimental group before and after treatment were （113,47±37.40）106/ml VS （34.32±21.46）106/ml （P〈0.01）, 72.21±16.52% VS 41.21±18.96%, 3.40±16.67 VS 34.22±19.10（P〈0.01）,70.64±9.35% VS 80.93±9.87%（P〈0.01）, 0.19±0.09% VS 2.52±0.38%（P〈0. 01）, respectively and showed significant difference. In comparison with the control group, same result was shown （P 〈0.01）. The sperm apoptosis was significantly correlated with the sperm parameters （P〈0.01）. Conclusion Oral-taking of Imatinib Mesylate for three months might lower the semen quality in male patients with chronic myelogenous leukemia and induce sperm apoptosis. Sperm analysis and cryopreservation should be performed before the treatment with Imatinib Mesylate to avoid male infertility.