治疗前血尿酸水平在初诊多发性骨髓瘤患者预后判断中的价值

Predictive Value of Pre-treatment Serum Uric Acid Level for Prognosis in Newly Diagnosed Patients with Multiple Myeloma

目的:研究初诊多发性骨髓瘤(NDMM)患者治疗前血尿酸(sUA)水平在其预后判断中的价值。方法:检索本中心2014年1月-2018年12月收治的NDMM患者资料,将初始治疗采用以硼替佐米为基础的化疗方案(≥4周期)且资料完整的94例患者纳入本研究。收集患者临床、实验室检查及随访资料,根据患者治疗前sUA水平及随访截止时的生存状态绘制受试者工作特征曲线,判断sUA对患者总体生存的预测价值,进一步分析sUA水平与患者的临床、实验室检查特征以及总体生存(OS)的相关性,采用单因素及多因素COX风险比例回归模型分析影响OS的因素。结果:受试者工作特征曲线分析显示,以sUA水平预测NDMM患者OS的曲线下面积为0.702(P <0.001),其最佳截断值为455.4μmol/L;相对于低sUA患者(<455.4μmol/L),高sUA(≥455.4μmol/L)患者国际分期系统分期Ⅲ期、高β2-微球蛋白(≥5.5 mg/L)、肾脏损害(血肌酐≥177μmol/L)、高钙血症(≥2.75 mmol/L)、高尿素氮(≥1×正常参考值上限)、伴高危细胞遗传学异常的比例更高(P <0.001)。中位随访22.5个月,低sUA患者的OS明显长于高sUA患者(中位OS:未达到vs 32个月,P=0.003)。单因素COX回归分析显示,年龄≥60岁、国际分期系统分期Ⅲ期、sUA≥455.4μmol/L、β2-微球蛋白≥5.5 mg/L、高钙血症≥2.75 mmol/L是影响患者OS的危险因素。多因素COX回归分析显示,仅年龄≥60岁(HR=2.317,95%CI:1.015-5.288,P=0.045)、sUA≥455.4μmol/L(HR=2.785,95%CI:1.054-7.361,P=0.039)是影响NDMM患者OS的独立危险因素。结论:治疗前sUA水平在NDMM患者的预后评估中具有一定的意义,有必要进一步探索和验证。

Objective: To evaluate the predictive value of pre-treatment serum uric acid( sUA) level for the prognosis of newly diagnosed multiple myeloma( NDMM) patients. Methods: The NDMM patients admitted to our center from January 2014 to December 2018 were analyzed retrospectively,and 94 patients among them who were initially treated with bortezomib-based chemotherapy for at least 4 cycles were included in this study. Clinical characteristics,laboratory data and follow-up information were collected,and the predictive value of sUA on the overall survival( OS) of NDMM was evaluated by using receiver operating characteristic( ROC) curve based on the patient’s pre-treatment sUA level and the survival status at the end of follow-up,and the correlation of the sUA level with patient’s clinical,laboratory characteristics and overall survival( OS) was further analyzed. The univariate and multivariate Cox proportional-hazards model were used to identify the potential factors affecting OS. Results: ROC analysis showed that the area under the curve for predicting OS in NDMM patients with sUA level was 0. 702( P <0. 001),and the optimal cut-off value was 455. 4 μmol/L. Compared to patients with low sUA( < 455. 4 μmol/L),patients with higher sUA( ≥455. 4 μmol/L) were more likely to have international staging system( ISS) stage III disease,beta2-microglobulin( β2-MG) ≥5. 5 mg/L,serum creatinine( sCr) ≥177 μmol/L,serum corrected calcium( cCa) ≥2. 75 mmol/L,urea nitrogen( BUN) ≥1 × upper limit of normal,and high-risk cytogenetic abnormality( all with P < 0. 001). At a median follow-up of 22. 5 months,the OS of NDMM with lower sUA was significantly better than higher sUA( median OS: not reached vs 32 months,P = 0. 003). Univariate COX regression analysis identified that age ≥60 years old,ISS stage III,sUA ≥455. 4 μmol/L,β2-MG ≥5. 5 mg/L,cCa ≥2. 75 mmol/L were risk factors affecting OS. The multivariate COX regression analysis that only age ≥60 years old( HR = 2. 317,95% CI:1. 015-5. 288,P = 0. 045) and sUA ≥455. 4 μmol/L( HR = 2. 785,95% CI: 1. 054-7. 361,P = 0. 039) were independent risk factors affecting OS. Conclusion: Pre-treatment sUA level is a potential biomarker for the prognosis evaluation in NDMM patients,which deserves a further exploration and verification.