多发性骨髓瘤患者硼替佐米治疗后周围神经病变的发生情况

Bortezomib-induced peripheral neuropathy in multiple myeloma patients

目的 观察多发性骨髓瘤（MM）患者应用硼替佐米过程中出现的不良反应,并重点分析周围神经病变的发生情况.方法 选择2009至2014年在浙江大学医学院附属第一医院血液科住院接受硼替佐米治疗的MM患者107例,收集相关病例资料,统计分析其治疗过程中不良反应的发生情况,尤其是周围神经病变在不同疗程和不同患者中的发生率.结果 107例接受硼替佐米治疗的患者中,40例（37%）患者出现周围神经病变,其中Ⅲ级神经毒性13 例,Ⅳ级0 例,38例患者在第1～4个疗程时出现神经毒性.其他常见不良反应依次为血小板减少、胃肠道反应、乏力、肺部感染、带状疱疹.44例严格按照硼替佐米1.3 mg/m2 标准剂量接受第1、4、8、11天治疗的患者中,周围神经病变发生20例（45%）,Ⅲ级周围神经病变发生6例（14%）;63例硼替佐米剂量〈1.3 mg/m2 治疗的患者中,20例（32%）出现周围神经病变,其中Ⅲ级周围神经病变发生7例（11%）;二者周围神经病变发生率差异无统计学意义（P=0.149） ,Ⅲ级周围神经病变发生率差异也无统计学意义（P=0.694）.单因素和多因素分析结果显示性别,年龄,治疗前是否合并高血压、糖尿病或者乙型肝炎病毒感染,治疗前是否存在神经系统症状,治疗前是否曾接受神经毒性药物治疗并非硼替佐米神经毒性的风险因素（均P〉0.05）.结论 降低硼替佐米的治疗剂量并未减少周围神经毒性的发生率,年龄、治疗前合并糖尿病或存在神经系统症状并非硼替佐米神经毒性的风险因素.

Objective To describe the side effects of bortezomib in treatment of multiple myeloma （MM）, especially the incidence of peripheral neuropathy （PN）.Methods Information of 107 patients with MM who were treated with bortezomib in the First Affiliated Hospital of Zhejiang University from 2009 to 2014,were collected and analyzed retrospectively , to analyze the occurrence of adverse events during the treatment, especially the incidences of PN in each cycle and in different patients.Results A total of 40 （37%） patients suffered from PN, among which 13 patients were grade 3 PN and no patients reported grade 4 PN.Other common treatment-related side effects were thrombocytopenia , gastrointestinal reactions , fatigue, lung infection, herpes zoster in turn.In 44 MM patients treated strictly with bortezomib 1.3 mg/m2 （days 1, 4, 8, 11） of each 3-week cycle, 20（45%） patients suffered from PN, of which 6 （14%） patients got grade 3 PN.In other 63 patients who received bortezomib less than 1.3 mg/m2 , 20 （32%） patients got PN and 7（11%） patients were grade 3 PN.There was no significant difference in the incidence of PN between the two groups of MM patients mentioned above （P=0.149） , as well as the incidence of grade 3 PN （P =0.694）.Univariate and multivariate analyse revealed that gender , age, a history of hypertensive disease , diabetes or hepatitis B virus infection , baseline PN symptoms and a history of neurotoxicity drug therapy were all not risk factors for PN （all P〉0.05）.Conclusions The reduction of bortezomib do not decrease the incidence of PN in bortezomib treatment of MM.Age, a history of diabetes and baseline PN symptoms are not risk factors for PN in bortezomib treatment of MM.