The role of inflammatory-nutritional indicators in predicting the prognosis and early mortality of newly diagnosed multiple myeloma patients
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摘要: 目的 探讨炎症-营养指标对新诊断多发性骨髓瘤(newly diagnosed multiple myeloma，NDMM)患者的预后及早期死亡的预测作用。方法 回顾性分析2015年8月至2022年2月在徐州医科大学附属医院初次诊断的161例NDMM患者的临床资料，包括年龄、性别、血红蛋白、白蛋白、乳酸脱氢酶(LDH)、血肌酐、血β2-微球蛋白、肿瘤负荷、浆细胞表面的CD27及CD56表达、荧光原位杂交检测细胞遗传学结果、是否合并髓外病变、是否合并脾大、预后营养指数(PNI)、炎症指标单核-淋巴细胞比值(MLR)、系统性免疫炎症指数以及治疗方案。对初诊时基线特征及治疗方案进行单因素及多因素Cox比例风险回归分析探索影响预后的因素，采用单因素及多因素logistic回归方法分析影响早期死亡的因素。结果 单因素Cox回归分析显示，血红蛋白、LDH、PNI、MLR、CD27是影响患者无进展生存时间的因素(P < 0.05)；年龄、LDH、PNI、MLR、CD27、CD56是影响患者总生存时间的因素(P < 0.05)。多因素Cox回归分析显示，高LDH、高MLR、CD27阴性是影响无进展生存时间的独立危险因素(P < 0.05)；年龄≥65岁、高LDH、低PNI、高MLR、1q21扩增阳性是影响总生存时间的独立危险因素(P < 0.05)。12个月内死亡和24个月内死亡的发生率分别为11.5%和24.2%。年龄≥65岁、浆细胞表面CD56阴性是12个月内死亡和24个月内死亡的独立影响因素；高LDH是12个月内死亡的独立影响因素；高MLR、低PNI是24个月内死亡的独立影响因素(均P < 0.05)。结论 低PNI、高MLR是影响NDMM患者预后的独立不良因素，可能预示患者早期死亡的风险增加。Abstract: Objective To investigate the prognostic role of inflammation-nutrition indicators in predicting the prognosis and early mortality of newly diagnosed multiple myeloma(NDMM) patients.Methods The clinical data of 161 patients with NDMM from August 2015 to February 2022 at the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. The clinical data included age, gender, hemoglobin, albumin, lactate dehydrogenase(LDH), creatinine, blood β2-microglobulin, tumor burden, CD27 and CD56 expression on plasma cell surface, cytogenetics detecting by fluorescence in situ hybridization, presence of extramedullary disease, splenomegaly, prognostic nutritional index(PNI), inflammation indicators monocyte-lymphocyte ratio(MLR), systemic immune inflammation index, and treatment regimens. Single-factor and multi-factor Cox proportional hazards regression analyses were conducted on baseline characteristics at initial diagnosis and treatment regimens to explore factors influencing prognosis; single-factor and multi-factor logistic regression methods were used to analyze factors affecting early mortality.Results Univariate Cox regression analysis showed that hemoglobin, LDH, PNI, MLR, and CD27 were factors affecting patients' progression-free survival(P < 0.05); age, LDH, PNI, MLR, CD27 and CD56 were factors affecting patients' overall survival(P < 0.05). Multivariate Cox regression analysis showed that high LDH, high MLR, and plasma cell surface CD27 negativity were independent risk factors affecting progression-free survival; age≥65 years, high LDH, low PNI, high MLR, and 1q21 amplification were independent adverse prognostic factors affecting overall survival(P < 0.05). The occurrence rates of death within 12 months(EM12) and 24 months(EM24) were 11.5% and 24.2%, respectively. Age≥65 years and plasma cell surface CD56 negativity were independent factors for both EM12 and EM24; high LDH was an independent factor for EM12; high MLR and low PNI were independent factors for EM24(P < 0.05).Conclusion Low PNI and high MLR are independent risk factors affecting the prognosis of NDMM patients and may indicate an increased risk of early mortality for patients.
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表 1 161例NDMM患者的临床特征
临床特征 例(%) 临床特征 例(%) 年龄/岁 β2-MG/(mg/L) < 65 95(59.0) < 3.5 95(59.0) ≥65 66(41.0) ≥3.5 66(41.0) 性别 细胞遗传学 女 68(42.2) 正常 11(6.8) 男 93(57.8) P53缺失 32(19.9) HGB/(g/L) 1q21扩增 116(72.0) ≥100 61(37.9) Rb缺失 74(46.0) < 100 100(62.1) IgH重排 142(88.2) Ca2+/(mmol/L) 13q14缺失 89(55.3) < 2.65 131(81.4) CD27 ≥2.65 30(18.6) 阳性 131(81.4) Alb/(g/L) 阴性 30(18.6) ≥40 46(28.6) CD56 < 0 115(71.4) 阳性 111(68.9) Cr/(μmol/L) 阴性 50(31.1) < 177 126(78.3) DS分期 ≥177 35(21.7) Ⅰ 14(8.7) LDH/(U/L) Ⅱ 39(24.2) < 250 127(78.9) Ⅲ 108(67.1) ≥250 34(21.1) ISS分期 PNI Ⅰ 57(35.4) ≥45 68(42.2) Ⅱ 72(44.7) < 45 93(57.8) Ⅲ 32(19.9) MLR 蛋白酶体抑制剂 < 0.225 76(47.2) 否 4(2.5) ≥0.225 85(52.8) 是 157(97.5) SII 免疫调节剂 < 474.81 115(71.4) 否 39(24.2) ≥474.81 46(28.6) 是 122(75.8) 骨髓浆细胞比例/% ASCT < 50 127(78.9) 否 115(71.4) ≥50 34(21.1) 是 46(28.6) 脾 正常 136(84.5) 增大 25(15.5) 
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表 2 NDMM患者PFS的单因素与多因素分析
临床特征 单因素分析 多因素分析 HR 95%CI P HR 95%CI P 年龄(≥65岁vs < 65岁) 1.502 0.999~2.258 0.050 1.147 0.717~1.833 0.568 性别(男vs女) 1.048 0.695~1.581 0.823 骨髓浆细胞比例(≥50% vs < 50%) 1.035 0.636~1.683 0.890 HGB(< 100 g/L vs ≥100 g/L) 1.660 1.069~2.578 0.024 1.472 0.926~2.338 0.102 Alb(< 40 g/L vs ≥40 g/L) 1.198 0.752~1.907 0.447 Cr(≥177 μmol/L vs < 177 μmol/L) 1.407 0.856~2.314 0.178 LDH(≥250 U/L vs < 250 U/L) 2.245 1.423~3.543 0.001 1.802 1.091~2.975 0.021 Ca2+(≥2.65 mmol/L vs < 2.65 mmol/L) 1.033 0.618~1.729 0.900 β2-MG(≥3.5 mg/L vs < 3.5 mg/L) 1.160 0.767~1.754 0.482 PNI(< 45 vs ≥45) 1.692 1.101~2.601 0.016 1.526 0.974~2.389 0.065 脾(增大vs正常) 0.717 0.399~1.290 0.267 初诊时合并EMD(是vs否) 1.277 0.771~2.115 0.342 MLR(≥0.225 vs < 0.225) 2.509 1.622~3.880 < 0.001 2.294 1.443~3.645 < 0.001 SII(≥474.81 vs < 474.81) 1.189 0.763~1.852 0.445 CD27(阴性vs阳性) 2.004 1.262~3.181 0.003 1.771 1.081~2.902 0.023 CD56(阴性vs阳性) 1.438 0.940~2.201 0.094 1.004 0.644~1.566 0.986 P53缺失(是vs否) 1.118 0.668~1.871 0.671 1q21扩增(是vs否) 1.323 0.830~2.106 0.239 Rb缺失(是vs否) 1.172 0.779~1.761 0.447 IgH重排(是vs否) 1.491 0.786~2.829 0.221 13q14缺失(是vs否) 1.066 0.707~1.607 0.760 蛋白酶体抑制剂(是vs否) 0.718 0.226~2.277 0.574 免疫调节剂(是vs否) 0.536 0.343~0.835 0.006 0.548 0.344~0.873 0.011 ASCT(是vs否) 0.415 0.245~0.702 0.001 0.488 0.277~0.858 0.013
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表 3 NDMM患者OS的单因素与多因素分析
临床特征 单因素分析 多因素分析 HR 95%CI P HR 95%CI P 年龄(≥65岁vs < 65岁) 2.359 1.408~3.951 0.001 1.837 1.020~3.309 0.043 性别(男vs女) 1.121 0.672~1.869 0.662 骨髓浆细胞比例(≥50% vs < 50%) 0.850 0.451~1.603 0.616 HGB(< 100 g/L vs ≥100 g/L) 1.441 0.835~2.486 0.190 Alb(< 40 g/L vs ≥40 g/L) 1.713 0.909~3.226 0.096 1.169 0.418~3.263 0.766 Cr(≥177 μmol/L vs < 177 μmol/L) 1.791 0.994~3.226 0.052 1.496 0.784~2.853 0.222 LDH(≥250 U/L vs < 250 U/L) 2.536 1.466~4.388 0.001 2.329 1.273~4.262 0.006 Ca2+(≥2.65 mmol/L vs < 2.65 mmol/L) 1.193 0.633~2.247 0.586 β2-MG(≥3.5 mg/L vs < 3.5 mg/L) 1.397 0.835~2.337 0.202 PNI(< 45 vs ≥45) 2.401 1.352~4.264 0.003 2.618 1.045~6.556 0.040 脾(增大vs正常) 0.978 0.507~1.886 0.946 初诊时合并EMD(是vs否) 1.150 0.597~2.217 0.675 MLR(≥0.225 vs < 0.225) 2.813 1.583~4.996 < 0.001 2.147 1.130~4.082 0.020 SII(≥474.81 vs < 474.81) 1.492 0.876~2.541 0.141 CD27(阴性vs阳性) 1.801 1.024~3.169 0.041 1.520 0.804~2.871 0.197 CD56(阴性vs阳性) 1.697 1.011~2.851 0.046 1.232 0.718~2.111 0.449 P53缺失(是vs否) 1.546 0.846~2.825 0.157 1q21扩增(是vs否) 1.704 0.938~3.095 0.080 2.325 1.177~4.594 0.015 Rb缺失(是vs否) 1.047 0.630~1.739 0.861 IgH重排(是vs否) 1.678 0.778~3.617 0.187 13q14缺失(是vs否) 0.942 0.566~1.567 0.819 蛋白酶体抑制剂(是vs否) 0.561 0.173~1.820 0.336 免疫调节剂(是vs否) 0.512 0.300~0.874 0.014 0.520 0.284~0.952 0.034 ASCT(是vs否) 0.315 0.149~0.664 0.002 0.448 0.203~0.989 0.047
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表 4 NDMM患者早期死亡的单因素分析
临床特征 12个月内死亡 24个月内死亡 OR 95%CI P OR 95%CI P 年龄(≥65岁vs < 65岁) 3.296 1.169~9.295 0.024 4.656 2.089~10.378 < 0.001 性别(男vs女) 2.047 0.693~6.047 0.195 0.890 0.422~1.880 0.761 骨髓浆细胞比例(≥50% vs < 50%) 0.434 0.095~1.986 0.282 0.396 0.129~1.210 0.104 HGB(< 100 g/L vs ≥100 g/L) 1.250 0.443~3.523 0.673 1.103 0.511~2.381 0.803 Alb(< 40 g/L vs ≥40 g/L) 1.045 0.350~3.118 0.937 1.879 0.758~4.658 0.173 Cr(≥177 μmol/L vs < 177 μmol/L) 3.437 1.240~9.529 0.018 1.538 0.657~3.603 0.321 LDH(≥250 U/L vs < 250 U/L) 4.720 1.702~13.086 0.003 2.799 1.225~6.394 0.015 Ca2+(≥2.65 mmol/L vs < 2.65 mmol/L) 0.859 0.232~3.179 0.820 1.070 0.418~2.744 0.887 β2-MG(≥3.5 mg/L vs < 3.5 mg/L) 0.906 0.332~2.474 0.847 1.388 0.658~2.927 0.390 PNI(< 45 vs ≥45) 1.531 0.544~4.307 0.420 3.231 1.366~7.639 0.008 脾(增大vs正常) 1.100 0.294~4.119 0.887 0.619 0.198~1.936 0.410 初诊时合并EMD(是vs否) 1.417 0.429~4.678 0.568 1.500 0.598~3.763 0.388 MLR(≥0.225 vs < 0.225) 3.549 1.114~11.305 0.032 5.105 2.081~12.523 < 0.001 SII(≥474.81 vs < 474.81) 2.865 1.057~7.763 0.039 1.849 0.847~4.040 0.123 CD27(阴性vs阳性) 1.286 0.391~4.225 0.679 1.338 0.538~3.325 0.531 CD56(阴性vs阳性) 5.526 1.938~15.759 0.001 2.906 1.350~6.258 0.006 P53缺失(是vs否) 2.250 0.773~6.548 0.137 2.179 0.931~5.099 0.073 1q21扩增(是vs否) 2.079 0.572~7.559 0.266 2.267 0.873~5.891 0.093 Rb缺失(是vs否) 0.722 0.265~1.968 0.524 0.924 0.439~1.948 0.836 IgH重排(是vs否) 2.448 0.307~19.525 0.398 2.676 0.588~12.174 0.203 13q14缺失(是vs否) 0.788 0.295~2.101 0.633 0.761 0.362~1.599 0.470 蛋白酶体抑制剂(是vs否) 0.364 0.036~3.701 0.393 0.276 0.038~2.035 0.207 免疫调节剂(是vs否) 0.265 0.097~0.727 0.010 0.551 0.244~1.243 0.151 ASCT(是vs否) < 0.001 0~∞ 0.991 0.173 0.050~0.598 0.006
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表 5 NDMM患者早期死亡的多因素分析
临床特征 12个月内死亡 24个月内死亡 OR 95%CI P OR 95%CI P 年龄(≥65岁vs < 65岁) 4.279 1.156~15.830 0.029 2.830 1.067~7.502 0.037 LDH(≥250 U/L vs < 250 U/L) 5.778 1.584~21.079 0.008 2.301 0.826~6.412 0.111 MLR(≥0.225 vs < 0.225) 1.070 0.252~4.544 0.927 4.191 1.487~11.814 0.007 CD56(阴性vs阳性) 4.857 1.463~16.132 0.010 2.976 1.157~7.653 0.024 Cr(≥177 μmol/L vs < 177 μmol/L) 1.272 0.337~4.806 0.723 SII(≥474.81 vs < 474.81) 2.539 0.673~9.579 0.169 免疫调节剂(是vs否) 0.308 0.090~1.062 0.062 PNI(< 45 vs ≥45) 3.960 1.326~11.825 0.014 P53缺失(是vs否) 2.828 0.944~8.471 0.063 1q21扩增(是vs否) 2.936 0.883~9.756 0.079 ASCT(是vs否) 0.263 0.063~1.088 0.065
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