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多发性骨髓瘤CD4/CD8比值和中性粒细胞与淋巴细胞比值的临床意义

Clinical significances of CD4/CD8 ratio and neutrophil-to-lymphocyte ratio in patients with multiple myeloma

摘要目的:探讨多发性骨髓瘤(MM)CD4/CD8比值和中性粒细胞与淋巴细胞比值(NLR)的临床意义。方法:回顾性分析2002年12月至2017年4月常州市第一人民医院收治的124例MM患者资料,选取31名体检健康者作为健康对照。应用流式细胞术检测外周血T细胞亚群,探讨CD4/CD8比值与MM患者相关临床指标的关系。按NLR中位值将MM患者分为高NLR组和低NLR组,分析NLR与相关临床指标、染色体核型、总生存(OS)、无进展生存(PFS)的关系。结果:与健康对照组相比,MM患者CD4 +细胞比例[(35.28±6.58)%比(31.85±6.76)%, t=-2.067, P=0.043]、NK细胞绝对值[0.22×10 9/L(0.13×10 9/L~0.59×10 9/L)比0.17×10 9/L(0.00×10 9/L~0.42×10 9/L), Z=-2.614, P=0.009]和CD4/CD8比值[0.97(0.50~2.69)比0.81(0.30~1.28), Z=-2.253, P=0.024]降低,CD8 +细胞比例升高[(36.93±7.38)%比(40.50±6.50)%, t=2.074, P=0.042]。MM患者CD4/CD8比值≥0.94组血红蛋白水平高于CD4/CD8比值<0.94组[(98.89±21.35)g/L比(80.60±23.23)g/L, t=-2.066, P=0.047]。与健康对照组相比,MM患者NLR增高[1.54(1.10~3.23)比1.95(0.29~12.70), Z=-2.384, P=0.017]。MM患者中,与低NLR(<1.95)组比较,高NLR(≥1.95)组血清β 2微球蛋白水平升高[4.56 mg/L(1.63~12.60 mg/L)比6.17 mg/L(1.58~67.50 mg/L), Z=-2.586, P=0.010]、血清肌酐升高[84.5 μmol/L(43.0~376.5 μmol/L)比113.0 μmol/L(46.5~754.0 μmol/L), Z=-3.866, P<0.01];高NLR组男性、β 2微球蛋白>5.5 mg/L、血清肌酐>177 μmol/L、国际分期系统(ISS)Ⅲ期患者比例均高于低NLR组(均 P<0.05);两组染色体核型构成差异均无统计学意义(均 P>0.05);低NLR组中位OS时间较高NLR组长[30个月(20~40个月)比17个月(7~27个月),χ 2=4.519, P=0.034];两组PFS差异无统计学意义( P>0.05)。多因素Cox回归分析显示,年龄、校正血钙、血清肌酐、乳酸脱氢酶是MM患者OS的独立影响因素(均 P<0.05),而NLR不是MM患者OS的独立影响因素( P=0.513)。 结论:MM患者CD4/CD8比值降低提示存在免疫功能失调。高NLR的MM患者OS时间缩短。

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abstractsObjective:To investigate the clinical significances of CD4/CD8 ratio and neutrophil-to-lymphocyte ratio (NLR) in patients with multiple myeloma (MM).Methods:The clinical data of 124 MM patients in the Third Affiliated Hospital of Soochow University from December 2002 to April 2017 were retrospectively analyzed, and 31 healthy people were chosen as the controls. Peripheral blood T lymphocyte subsets were detected by using flow cytometry, and the correlations between CD4/CD8 ration and related clinical indicators were also investigated. All MM patients were divided into the high NLR group and the low NLR group according to the media of NLR, and the correlation of them with related clinical indicators, chromosome karyotype, overall survival (OS) and progression-free survival (PFS) was also compared.Results:Compared with the healthy control group, the proportion of CD4 + T cells [(35.28±6.58)% vs. (31.85±6.76)%, t = -2.067, P = 0.043], absolute value of NK cells [0.22×10 9/L (0.13×10 9/L-0.59×10 9/L) vs. 0.17×10 9/L (0.00×10 9/L-0.42×10 9/L), Z = -2.614, P = 0.009] and CD4/CD8 ratio [0.97 (0.50-2.69) vs. 0.81 (0.30-1.28), Z = -2.253, P = 0.024] was decreased, respectively. The proportion of CD8 + cells was increased [(36.93±7.38)% vs. (40.50±6.50)%, t = 2.074, P = 0.042] in MM group. The hemoglobin level of CD4/CD8 ratio ≥0.94 group was higher than that of CD4/CD8 ratio <0.94 [(98.89±21.35) g/L vs.(80.60±23.23) g/L, t = -2.066, P = 0.047]. Compared with the healthy control group, NLR was increased in MM group [1.54 (1.10-3.23) vs. 1.95 (0.29-12.70), Z = -2.384, P = 0.017]. Compared with the low NLR group (<1.95), serum β 2-microglobulin [4.56 mg/L (1.63-12.60 mg/L) vs. 6.17 mg/L (1.58-67.50 mg/L), Z = -2.586, P = 0.010] and serum creatinine [84.5 μmol/L (43.0-376.5 μmol/L) vs. 113.0 μmol/L (46.5-754.0 μmol/L), Z = -3.866, P < 0.001] was increased in the high NLR group for MM patients. The proportion of the male patients, β 2-microglobulin > 5.5 mg/L, serum creatinine > 177 μmol/L, stage Ⅲ of international staging system (ISS) in the high NLR group was higher than that in the low NLR group (all P < 0.05), and there was no statistically significant difference in the composition of chromosome karyotype (all P > 0.05). The median OS time in the low NLR group was longer than that in the high NLR group [30 months (20-40 months) vs. 17 months (7-27 months), χ 2 = 4.519, P = 0.034], and there was no statistically significant difference in the PFS of both groups ( P > 0.05). Multivariate Cox analysis demonstrated that the age, corrected serum calcium, serum creatinine, lactic dehydrogenase were the independent influencing factors of OS in MM (all P < 0.05), while NLR wasn′t an independent influencing factor of OS in MM ( P = 0.513). Conclusions:CD4/CD8 ratio is decreased and immune dysfunction occurs in MM patients. MM patients with high NLR have a shorter OS time.

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