多发性骨髓瘤治疗中硼替佐米相关周围神经病变发生的危险因素及患者临床特征、电生理特点分析

Risk factors of bortezomib-related peripheral neuropathy and the clinical features and electrophysiological characteristics of patients during treatment of multiple myeloma

目的探讨多发性骨髓瘤(MM)治疗中硼替佐米相关周围神经病变(BIPN)发生的危险因素及患者的临床特征、电生理特点。方法回顾性分析2016年3月至2019年12月盐城市第一人民医院应用BD(硼替佐米+地塞米松)方案治疗的71例初诊MM患者的临床资料,获得骨髓形态学、免疫学、细胞遗传学、分子生物学(MICM)检查、治疗前后常规电生理检查结果。根据是否发生BIPN将71例患者分为周围神经病变(PN)组和非PN组,比较两组临床病理特征差异;采用二元logistic回归模型分析发生PN的影响因素。总结BIPN患者电生理特点及采用荧光原位杂交(FISH)检测的染色体核型情况。结果71例MM患者中,PN 40例(56.3%),非PN 31例(43.7%)。PN组国际分期系统(ISS)分期Ⅲ期患者比例及IgA、IgG、IgM、血肌酐、β_(2)-微球蛋白(β_(2)-MG)水平均高于非PN组,血红蛋白(Hb)水平均低于非PN组,差异均有统计学意义(均P<0.05)。二元logistic回归分析显示,IgA升高(OR=1.151,95%CI 1.012~1.309,P=0.033)、IgG升高(OR=1.055,95%CI 1.000~1.112,P=0.049)、IgM升高(OR=1.010,95%CI 1.001~1.018,P=0.022)、血肌酐升高(OR=1.037,95%CI 1.011~1.065,P=0.005)、β_(2)-MG升高(OR=1.564,95%CI 1.039~2.354,P=0.032)为BIPN发生的危险因素。40例BIPN患者中,感觉神经传导速度(SCV)异常33例(82.5%),运动神经传导速度(MCV)异常23例(57.5%);31例(77.5%)表现为脱髓鞘损害,9例(22.5%)为轴突损害。40例BIPN患者中24例行FISH检测,其中染色体突变19例(79.2%),包括混合型异常12例(50.0%)。结论硼替佐米治疗MM时,β_(2)-MG、IgA、IgG、IgM、血肌酐水平高的患者更易发生PN。BIPN患者电生理主要呈感觉神经脱髓鞘病变特点。

Objective To explore the risk factors of bortezomib-related peripheral neuropathy(BIPN)and the clinical and electrophysiological characteristics of patients in treatment of multiple myeloma(MM).Methods The clinical data of 71 newly diagnosed MM patients treated with BD(bortezomib+dexamethasone)regimen in Yancheng First People's Hospital from March 2016 to December 2019 were retrospectively analyzed.The bone marrow morphology,immunology,cytogenetics,molecular biology(MICM),routine electrophysiological examination before and after treatment were performed.All patients were divided into the peripheral neuropathy(PN)group and the non-PN group according to the presence or not of BIPN,and the clinicopathological differences of both groups were also compared;a binary logistic regression model was used to analyze the factors affecting the occurrence of PN.The electrophysiological characteristics were summarized and fluorescence in situ hybridization(FISH)was used to detect karyotype of BIPN patients.Results Among 71 MM patients,there were 40 cases(56.3%)of PN and 31 cases(43.7%)of non-PN.The proportion of patients at international staging system(ISS)stagingⅢ,and the levels of IgA,IgG,IgM,serum creatinine,β_(2)-microglobulin(β_(2)-MG)in the PN group were higher than those in the non-PN group,and hemoglobin(Hb)level in the PN group was lower than that in the non-PN group,and the differences were statistically significant(both P<0.05).Binary logistic regression analysis showed that increased IgA(OR=1.151,95%CI 1.012-1.309,P=0.033),increased IgG(OR=1.055,95%CI 1.000~1.112,P=0.049),increased IgM(OR=1.010,95%CI 1.001-1.018,P=0.022),increased serum creatinine(OR=1.037,95%CI 1.011~1.065,P=0.005),increased β_(2)-MG(OR=1.564,95%CI 1.039-2.354,P=0.032)were risk factors for BIPN.Among 40 patients with BIPN,33 cases(82.5%)of sensory nerve conduction velocity(SCV)were abnormal,23 cases(57.5%)of motor nerve conduction velocity(MCV)were abnormal;31 cases(77.5%)showed demyelination damage,9 cases(22.5%)had axonal damage.Among 40 patients with BIPN,24 cases underwent FISH detection,including 19 cases(79.2%)with chromosomal mutations,of which 12 cases(50.0%)were mixed subtype abnormal.Conclusions MM patients with high levels of β_(2)-MG,IgA,IgG,IgM and serum creatinine are more prone to PN when treated with bortezomib.The electrophysiology of patients with BIPN is mainly characterized by demyelination of sensory nerves.