多发性骨髓瘤患者血清可溶性白细胞介素-6受体水平的临床意义

Clinical Significance of Serum Soluble Interleukin-6 Receptor Level in Multiple Myeloma

目的 研究血清可溶性白细胞介素-6受体（sIL-6R）与多发性骨髓瘤（MM）疗效及预后的关系,并探索其临床意义.方法 选择2006年7月至2011年12月,于首都医科大学附属北京朝阳医院血液科住院的67例初治为MM的患者为研究对象.按年龄将其分为：老年组（＞65岁,n=20）和年轻组（≤65岁,n=47）;再按照Durie-Salmon（DS）分期标准将其分为：Ⅰ/Ⅱ期组（n=8）和Ⅲ期组（n=59）;按照国际分期体系（ISS）分期标准将其分为：Ⅰ期组（n=6）,Ⅱ期组（n=19）和Ⅲ期组（n=42）;按照免疫分型标准将其分为：IgA型组（n=19）,IgG型组（n=23）,轻链型组（n=19）以及其他类型组（n=6）;按照中位血清sIL-6R水平,将其分为sIL-6R≤500 ng/L组（n=43）和＞500 ng/L组（n=24）.MM患者经4～6个疗程治疗后,能够评价疗效的患者为29例,按照疗效将其分为获得部分缓解（PR）及以上疗效组（n=25）和未达PR组（n=4）.（本研究遵循的程序符合首都医科大学附属北京朝阳医院人体试验委员会所制定的伦理学标准,分组征得受试对象本人的知情同意,并与之签订临床研究知情同意书）.采用酶联免疫吸附法（ELISA）检测患者血清sIL-6R水平上,比较其在不同年龄组、不同免疫分型组、不同临床分期组患者中的表达,并分析血清sIL-6R水平与患者疗效以及生存之间的关系.结果 老年组MM患者的血清sIL-R6水平为（496.6±204.4）ng/L与年轻组的（494.8±260.0）ng/L相近,两组比较差异无统计学意义（t=0.027,P=0.98）;IgG型患者的sIL-6R水平最高[（590.6±285.5） ng/L],轻链型患者次之[（475.6±253.0） ng/L],lgA型患者最低[（418.0±137.1） ng/L],但3组比较差异无统计学意义（F=2.895,P＞0.05）.DS分期Ⅰ/Ⅱ患者的sIL-6R水平为（598.1±347.2）ng/L较Ⅲ期组的（482.3±226.5）ng/L高,但两组间差异无统计学（t=1.199,P=0.23）.ISS分期Ⅰ期组患者sIL-6R水平为（469.5±271.4）ng/L较Ⅱ期组[（510.9±239.9）]ng/L和Ⅲ期组[（492.1±146.4）]ng/L低,但3组相比差异无统计学意义（F=0.074,P＞0.05）.MM患者接受治疗后,获得部分缓解（PR）及以上疗效组患者的sIL-6R水平较治疗前降低（t=1.759,P=0.08）,未获得PR疗效患者的sIL-6R水平较治疗前有所升高（t=0.285,P=0.78）.sIL-6R水平≤500 ng/L患者的中位生存期较＞500 ng/L组患者长（32.3个月比19.6个月）,但两组相比差异无统计学意义（P=0.18）.结论 MM患者的sIL-6R水平与患者年龄、分期和分型的关系不明确,但与疗效和生存预后有一定关系.

Objective To study the relationship between serum soluble interleukin 6 receptor （sIL-6R） and treatment efficacy and prognosis of multiple myeloma （MM）,and explore its clinical significance of sIL-6R.Methods Form July 2006 to December 2011,67 MM patients who received treatment in Beijing Chaoyang hospital,Capital Medical University were selected into this study.According to age of patents,they were divided into the older group （＞65 years old,n=20） and young group （≤65 years old,n=47）.According to Durie-Salmon （DS） staging criteria,the patients were divided into DS Ⅰ/Ⅱ stage group （n=8） and Ⅲ stage group （n=59）.According to the International Staging system （ISS） criteria,the patients were divided into ISS Ⅰ stage group （n 6）,stage Ⅱ stage group （n 19） and Ⅲ stage group （n=42）.According to the immune classification criteria,the patients were divided into IgA group （n=19）,IgG group （n=23）,light chain group （n=19） and other types group （n 6）.According to the median serum sIL-6R levels of patients,they were divided into sIL-6R≤500 ng/ L group （n 43） and ＞500 ng/L group （n 24）.After four to six courses of treatment,there were 29 cases of MM patients could evaluate the efficacy.According to the efficacy of patients,they were divided into ≥partial remission （PR） group （n 25）and ＜PR group （n=4）.（The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Beijing Chaoyang hospital.Informed consent was obtained from all participants.） The serum levels of sIL-6R were detected by enzyme-linked immunosorbent assay technique in 67 patients with MM.The serum sIL-6R levels of MM patients in different ages,immunophenotypes and clinical stages were compared.The relationship between serum levels of sIL-6R between patient outcomes and survival were analyzed.Results sIL-6R levels of MM patients in older group were （496.6±204.4） ng/L,which were similar with the young group[（494.8±260.0） ng/L）] （t=0.027,P=0.98）.Patients in IgA type group had lower sIL-6R levels [（418.0±137.1） ng/L] than those of IgG type group [（590.6±285.5） ng/L] and light chain type group [（475.6±253.0） ng/L],but there were no statistical significance among these three groups （F=2.895,P＞0.05）.Patients with DS stage Ⅰ/Ⅱ had higher sIL-6R levels [（598.1± 347.2） ng/L] than those of stage Ⅲ [（482.3±226.5） ng/L],and it also had no statistical significance （t=1.199,P＞0.05）.Patients with ISS stage Ⅰ had lower sIL-6R levels [（469.5±271.4） ng/L] than those of stage Ⅱ [（510.9±239.9） ng/L] and stage Ⅲ [（492.1 ± 146.4） ng/L],and it also had no statistical significance （F 0.074,P＞0.05）.After treatment,patients who obtained PR or more had decrease of sIL-6R levels （t=1.759,P=0.08）,patients who obtained less than PR had increase of sIL-6R levels （t =0.285,P=0.78）.Patients with sIL-6R ≤500 ng/L had longer overall survival time than those of ＞ 500 ng/L （32.3 months vs.19.6 months）,however their had no statistical significance （P=0.18）.Conclusions Serum sIL-6R levels of MM patients had no association with age,clinical stages and immunophenotype.There maybe a certain relationship among sIL 6R levels of MM patients,efficacy and survival prognosis.