Relationship between LMR, PNI and chemotherapy response and prognosis in patients with multiple myeloma
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摘要:
目的 探讨淋巴细胞单核细胞比值(LMR)和预后营养指数(PNI)对多发性骨髓瘤(MM)患者化疗反应及预后的影响。 方法 选取2016年3月—2022年5月新乡医学院第一附属医院收治的MM患者243例。收集化疗前1周患者的实验室检查指标，计算LMR和PNI，并根据中位数分为低PNI组(＜47.2，121例)和高PNI组(≥47.2，122例)，低LMR组(＜5.85，120例)和高LMR组(≥5.85，123例)。比较不同分组患者的临床资料、化疗疗效和预后差异，并对接受硼替佐米的患者进行亚组分析。 结果 高PNI组和低PNI组的化疗疗效差异无统计学意义(P>0.05)，低LMR组和高LMR组的化疗疗效差异无统计学意义(P>0.05)。经过1~92个月随访，110例患者死亡，133例存活。低PNI组的中位总生存期(OS)较高PNI组缩短(31个月vs. 39个月，χ2=4.130，P＜0.05)，低LMR组的中位总生存期(OS)较高LMR组缩短(31个月vs. 41个月，χ2=10.308，P＜0.01)。在接受以硼替佐米为基础的化疗方案的136患者中，低PNI组中位OS与高PNI组差异无统计学意义(30个月vs. 36个月，χ2=2.814，P＞0.05)；低LMR组的中位OS较高LMR组缩短(30个月vs.未达到，χ2=7.618，P＜0.05)。Cox回归分析结果显示，低PNI和低LMR是患者OS的独立危险因素。 结论 PNI和LMR可作为MM患者简单可靠的预后指标，可早期识别高危患者，但无法预测患者的化疗疗效。 -
关键词:
- 多发性骨髓瘤 /
- 淋巴细胞单核细胞比值 /
- 预后营养指数 /
- 化疗疗效 /
- 预后
Abstract:Objective To investigate the effects of lymphocyte-monocyte ratio (LMR) and prognostic nutritional index (PNI) with chemotherapy response and prognosis in patients with multiple myeloma (MM). Methods A total of 243 MM patients admitted to the First Affiliated Hospital of Xinxiang Medical University from March 2016 to May 2022 were selected. LMR and PNI were calculated. According to the median, patients were divided into PNI group (< 47.2, 121 cases) and high PNI group (≥47.2, 122 cases), high LMR group (≥5.85, 123 cases) and low LMR group (< 5.85, 120 cases). The clinical data, chemotherapy efficacy and prognosis of patients in different groups were compared, and subgroup analysis of patients receiving bortezomib was performed. Results There was no significant difference in the efficacy of chemotherapy between the high PNI group and the low PNI group (P>0.05), and there was no significant difference in the efficacy of chemotherapy between the low LMR group and the high LMR group (P>0.05). After 1 to 92 months of follow-up, 110 patients died and 133 patients survived. The median OS of the low PNI group was shorter than that of the PNI group (31 months vs. 39 months, χ2=4.130, P < 0.05), and the median OS of the low LMR group was shorter than that of the high LMR group (31 months vs. 41 months, χ2= 10.308, P < 0.01). Among 136 patients who received bortezomib-based chemotherapy, there was no significant difference in median OS between the low and high PNI groups (30 months vs. 36 months, χ2=2.814, P>0.05). The median OS of the low LMR group was shorter than that of the LMR group (30 months vs. not reached, χ2=7.618, P < 0.05). Cox regression analysis showed that low PNI and low LMR were independent risk factors for OS. Conclusion PNI and LMR can be used as simple and reliable prognostic indicators for MM patients. PNI and LMR can identify high-risk patients early, but cannot predict response to chemotherapy. -
图 1 不同PNI和LMR分组MM患者的生存曲线
注：A为不同PNI分组MM患者的生存曲线；B为不同LMR分组MM患者的生存曲线。
Figure 1. Comparison of PNI and LMR survival curves in MM patients
图 2 在接受以硼替佐米为基础的化疗方案的MM患者中不同PNI和LMR分组的生存曲线
注：A为不同PNI分组MM患者的总生存曲线；B为不同LMR分组MM患者的总生存曲线。
Figure 2. Comparison of PNI and LMR survival curves in MM patients treated with bortezomib-based chemotherapy regimens
表 1 不同PNI分组MM患者临床病理特征比较
Table 1. Comparison of clinicopathological features of MM patients in different PNI groups
组别 例数 年龄
(x±s，岁)性别
(男性/女性，例)BMI
(x±s)浆细胞比例
[M(P25, P75)，%]β2-微球蛋白
[M(P25, P75)，g/L]红细胞计数
(x±s，×109/L)血红蛋白
(x±s，g/L)中性粒细胞计数
[M(P25, P75)，×109/L]高PNI组 122 64.96±8.87 67/55 23.32±3.50 34.75(16.88，61.00) 3.70(2.37，7.09) 3.17±1.07 97.43±23.37 3.17(2.44，4.31) 低PNI组 121 67.37±9.48 71/50 22.87±3.30 44.00(23.25，68.25) 4.88(3.32，9.24) 2.54±0.72 80.79±23.03 2.89(1.88，4.34) 统计量 2.048a 0.350b 1.041a 1.841c 2.717c 5.390a 5.590a 1.508c P值 0.042 0.554 0.299 0.066 0.007 < 0.001 < 0.001 0.131 组别 例数 单核细胞计数
[M(P25, P75)，×109/L]淋巴细胞计数
[M(P25, P75)，×109/L]血糖
(x±s，mmol/L)肌酐
[M(P25, P75)，μmoI/L]尿酸
[M(P25, P75)，μmoI/L]白蛋白
(x±s，g/L)乳酸脱氢酶
[M(P25, P75)，U/L]ISS分期
(Ⅰ/Ⅱ/Ⅲ，例)高PNI组 122 0.32(0.22，0.42) 1.45(1.02，1.95) 5.43±2.11 76.6(54.5，160.1) 343(225，448) 39.80±4.92 182.5(154.8，233.2) 42/31/49 低PNI组 121 0.24(0.17，0.40) 1.05(0.71，1.52) 5.28±1.66 73.9(57.3，127.8) 328(255，488) 29.38±5.58 173.0(128.0，239.5) 9/56/56 统计量 2.925c 4.436c 0.624a 0.102c 0.806c 15.956a 1.357c 2.014c P值 0.003 < 0.001 0.533 0.918 0.420 < 0.001 0.175 < 0.001 注：a为t值，b为χ2值，c为Z值。 
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表 2 不同LMR分组MM患者临床病理特征比较
Table 2. Comparative analysis of clinicopathological features among patients with varying LMR
组别 例数 年龄
(x±s，岁)性别
(男性/女性，例)BMI
(x±s)浆细胞比例
[M(P25, P75)，%]β2-微球蛋白
[M(P25, P75)，g/L]红细胞计数
(x±s，×109/L)血红蛋白
(x±s，g/L)中性粒细胞计数
[M(P25, P75)，×109/L]低LMR组 120 66.56±10.19 72/48 22.93±3.45 43.0(22.5，70.0) 4.75(3.07，8.48) 2.88±1.06 89.56±24.55 3.26(2.38，4.80) 高LMR组 123 65.77±8.24 66/57 23.26±3.37 38.0(18.0，57.5) 4.21(2.63，8.08) 2.83±0.87 88.66±24.76 2.82(1.95，3.88) 统计量 0.662a 0.995b 0.767a 1.559c 0.937c 0.459a 0.313a 1.993c P值 0.509 0.754 0.444 0.110 0.349 0.647 0.241 0.046 组别 例数 单核细胞计数
[M(P25, P75)，×109/L]淋巴细胞计数
[M(P25, P75)，×109/L]血糖
(x±s，mmol/L)肌酐
[M(P25, P75)，μmoI/L]尿酸
[M(P25, P75)，μmoI/L]白蛋白
(x±s，g/L)乳酸脱氢酶
[M(P25, P75)，U/L]ISS分期
(Ⅰ/Ⅱ/Ⅲ，例)低LMR组 120 0.35(0.24，0.50) 1.14(0.80，1.52) 5.50±1.73 76.0(59.0，179.3) 339(225，495) 34.81±7.30 188(139，241) 24/38/58 高LMR组 123 0.22(0.16，0.32) 1.43(0.98，1.90) 5.22±2.05 74.9(53.0，112.5) 343(253，449) 34.42±7.28 173(144，215) 27/49/47 统计量 4.926c 3.078c 1.151a 1.802c 0.190c 0.418a 0.989c 1.320c P值 0.001 0.002 0.251 0.071 0.849 0.676 0.323 0.187 注：a为t值，b为χ2值，c为Z值。
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表 3 高PNI组和低PNI组MM患者临床疗效比较[例(%)]
Table 3. Comparison of clinical efficacy between high PNI group and low PNI group[cases(%)]
组别 例数 未评估 部分缓解 完全缓解 未缓解 复发进展 高PNI组 122 18(14.8) 33(27.0) 21(17.2) 25(20.5) 25(20.5) 低PNI组 121 19(15.7) 31(25.6) 20(16.5) 17(14.0) 34(28.1) 注：2组疗效比较，Z=0.593，P=0.874。
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表 4 高LMR组和低LMR组MM患者临床疗效比较[例(%)]
Table 4. Comparative analysis of clinical efficacy in MM patients between the high LMR and low LMR groups[cases(%)]
组别 例数 未评估 部分缓解 完全缓解 未缓解 复发进展 低LMR组 120 18(15.0) 32(26.7) 23(19.2) 21(17.5) 26(21.7) 高LMR组 123 19(15.4) 32(26.0) 18(14.6) 21(17.1) 33(26.8) 注：2组疗效比较，Z=0.402，P=0.997。
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表 5 单因素Cox回归分析MM患者OS的影响因素
Table 5. Univariate Cox regression analysis of factors influencing OS in MM patients
变量 B SE Wald χ2 P值 HR值 95% CI 年龄 0.010 0.010 0.910 0.340 1.010 0.990~1.030 ISS分期 0.340 0.133 6.499 0.011 1.405 1.082~1.825 浆细胞比例 0.004 0.004 1.009 0.315 1.004 0.996~1.011 β2-微球蛋白 0.012 0.008 2.032 0.154 1.012 0.996~1.028 红细胞计数 -0.268 0.118 5.216 0.022 0.765 0.607~0.963 血红蛋白 -0.007 0.004 3.322 0.068 0.993 0.985~1.001 中性粒细胞计数 0.061 0.038 2.582 0.108 1.063 0.987~1.145 单核细胞计数 0.300 0.120 6.211 0.013 1.350 1.066~1.708 淋巴细胞计数 0.012 0.031 0.163 0.686 1.012 0.954~1.075 血糖 0.013 0.047 0.075 0.784 1.013 0.924~1.110 肌酐 0.001 < 0.001 2.823 0.093 1.001 1.000~1.002 白蛋白 -0.029 0.013 5.049 0.025 0.971 0.947~0.996 乳酸脱氢酶 0.001 < 0.001 8.298 0.004 1.001 1.000~1.001 PNI 0.388 0.194 3.999 0.046 1.475 1.008~2.157 LMR 0.659 0.201 10.766 0.001 1.932 1.304~2.864
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表 6 影响MM患者OS的多因素Cox回归分析
Table 6. Multivariate Cox regression analysis of multiple factors affecting OS in MM patients
变量 B SE Wald χ2 P值 HR值 95% CI 红细胞计数 -0.082 0.139 0.345 0.557 0.922 0.702~1.210 单核细胞计数 0.094 0.112 0.703 0.402 1.098 0.882~1.367 白蛋白 -0.070 0.020 12.024 0.001 0.933 0.897~0.970 乳酸脱氢酶 0.001 < 0.001 10.438 0.001 1.001 1.000~1.001 PNI 1.369 0.298 21.157 < 0.001 3.933 2.194~7.048 LMR 0.510 0.211 5.861 0.015 1.665 1.102~2.515 ISS分期 0.519 0.203 6.536 0.011 1.680 1.129~2.541
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