Efficacy influencing factors analysis and prediction model establishment of apheresis platelet transfusion in patients with myelodysplastic syndrome
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摘要: 目的 探讨骨髓增生异常综合征(myelodysplastic syndromes，MDS)患者去白细胞单采血小板输注疗效的影响因素，建立MDS患者血小板输注效果预测模型，为MDS患者血小板输注的时机选择、效果预判提供参考因素。方法 回顾性分析2020年1月1日—2022年12月31日医院住院确诊的130例次输注血小板的MDS患者，根据输血后血小板校正计数增量(CCI)将患者分为有效组和无效组，1 h CCI < 7.5×109/L或16~24 h CCI < 4.5×109/L判为无效，1 h CCI≥7.5×109/L或16~24 h CCI≥4.5×109/L判为有效，收集2组患者资料。首先进行简单差异性分析；然后通过二元logistic回归分析血小板输注无效的独立影响因素，利用回归系数及常数项建立血小板输注疗效预测模型；最后采用受试者工作特征(ROC)曲线评估模型对MDS患者血小板输注疗效的预估价值。结果 83例MDS患者中，25例(30.12%)输注血小板，输注血小板总例次130例。血小板输注有效率60.77%(79/130)，无效率39.23%(51/130)。2组在是否使用升血小板药、是否有并发症(心血管疾病、感染、糖尿病)、输血前中性粒细胞/淋巴细胞比值(NLR)等方面差异无统计学意义(P>0.05)；在性别、输血时限、输血前血小板计数(PLT)、输注血小板袋数、输血前淋巴细胞/单核细胞比值(LMR)、输血前血小板/淋巴细胞比值(PLR)、是否化疗、使用抗生素、并发症(慢性胃炎、脾肿大)、出血事件等方面差异有统计学意义(P < 0.05)；男性患者，有脾肿大、化疗、使用抗生素时血小板输注无效率增大，输血前PLT、输血前LMR、输血前PLR与血小板输注有效率呈正相关，输注血小板袋数与输注无效率呈正相关。二元logistic分析显示脾肿大(OR=0.036，95%CI 0.009~0.138，P=0.002)、化疗(OR=0.088，95%CI 0.008~1.003，P=0.045)、血小板输注袋数(OR=0.845，95%CI 0.763~0.936，P=0.001)是影响MDS患者血小板输注无效的独立危险因素。ROC曲线显示：脾肿大、化疗、输注血小板袋数三因素联合预测模型的预估价值优于单因素预测模型，联合预测模型曲线下面积、特异度、灵敏度分别为0.900(95%CI 0.839~0.961)、85.40%、85.41%。血小板输注袋数作单因素预测模型时截断值为5.5袋。结论 血小板输注袋数>5袋、脾肿大、化疗是MDS患者血小板输注无效的独立危险因素，MDS患者血小板输注疗效可以通过多因素预测模型进行预估，结合患者出血风险，可为MDS患者血小板输注选择合适时机。Abstract: Objective To explore the factors influencing the efficacy of leukocytodeplastised platelet monocytotomy (platelet) infusion for patients with myelodysplastic syndromes (MDS), and establish a prediction model for platelet infusion for MDS patients, so as to provide reference factors for the timing and effect prediction of platelet infusion for MDS patients.Methods A retrospective analysis of 130 patients with MDS who were admitted to the hospital with platelet infusion from January 1, 2020 to December 31, 2022 was conducted, and the patients were divided into an effective group and an ineffective group according to the platelet-corrected count increment (CCI) after transfusion. 1 h CCI < 7.5×109/L or 16-24 h CCI < 4.5×109/L was deemed invalid, 1 h CCI≥7.5×109/L or 16-24 h CCI≥4.5×109/L was deemed valid. Relevant information and data of the two groups of patients were collected. Firstly, a simple difference analysis was carried out. Then, the independent influencing factors of platelet ineffectiveness were analyzed by binary logistic regression, and the predictive model of platelet infusion efficacy was established using regression coefficient and constant terms. Finally, receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the model for platelet infusion in MDS patients.Results Of 83 MDS patients, 25 cases (30.12%) received platelet infusion, and 130 case-time received platelet infusion. The effective rate of platelet infusion was 60.77% (79/130), and the inefficiency was 39.23% (51/130). There were no statistically significant differences between the two groups in use of platelet enhancers, complications(cardiovascular disease, infection, diabetes), and neutrophil/lymphocyte ratio(NLR) before transfusion(P>0.05). There were statistically significant differences in gender, time limit of transfusion, platelet count before transfusion, platelet bag number, lymphocyte/monocyte ratio(LMR) before transfusion, platelet/lymphocyte ratio(PLR) before transfusion, whether chemotherapy was used, antibiotics, complications(chronic gastritis, splenomegalia), and bleeding events(P < 0.05). In male patients, spleen enlargement, chemotherapy, and increased platelet transfusion inefficiency were observed. PLT count before transfusion, LMR before transfusion, PLR before transfusion were positively correlated with platelet transfusion rate, and the number of platelet bags was positively correlated with infusion inefficiency. Binary logistic analysis showed spleen enlargement(OR=0.036, 95%CI 0.009-0.138, P=0.002) and chemotherapy(OR=0.088, 95%CI 0.008-1.003, P=0.045) and the number of platelet infusion bags(OR=0.845, 95%CI 0.763-0.936, P=0.001) were independent risk factors for ineffective platelet infusion in MDS patients. ROC curve showed that the prediction value of the combined prediction model of three factors, such as spleen enlargement, chemotherapy and platelet bag number, was better than that of the single factor prediction model. The area, specificity and sensitivity of the combined prediction model under the curve were 0.900(95%CI 0.839-0.961), 85.40% and 85.41%, respectively. When the number of platelet infusion bags was used as the single factor prediction model, the cut-off value was 5.5.Conclusion The number of platelet transfusion bags>5, splenomegalysis and chemotherapy may be independent risk factors for ineffective platelet transfusion in MDS patients. The efficacy of platelet transfusion in MDS patients can be estimated by using a multi-factor prediction model, and the appropriate time for platelet transfusion in MDS patients can be selected combined with the risk of bleeding.
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表 1 MDS输注血小板患者基本信息与各因素下血小板输注疗效
变量 总例数(n=130) 有效组(n=79) 无效组(n=51) χ2/Z P 性别 13.832 < 0.001 女 32(24.6) 29(90.63) 3(9.37) 男 98(75.4) 53(54.08) 45(45.92) 年龄/岁 72(27) 72(7) 58(39) 1.985 0.047 输注前PLT/(×109/L) 9.5(5，16) 11(7，18) 7(3，12.75) 9.241 0.026 0~5 32(24.6) 14(56.3) 18(43.7) 6~10 33(25.4) 21(63.6) 12(36.4) 11~20 50(38.8) 34(68.0) 16(32.0) ≥21 15(11.2) 13(86.7) 2(13.3) 输注血小板袋数/袋 6(2，11) 3(2，7) 10.5(7，16) 33.035 < 0.001 1~5 64(49.2) 56(87.5) 8(12.5) 6~10 30(23.1) 14(46.7) 16(53.3) 11~15 18(13.8) 7(38.9) 11(61.1) ≥16 18(13.8) 5(27.8) 13(71.2) 化疗 18.661 < 0.001 是 96(73.8) 71(74.0) 25(26.0) 否 34(24.2) 11(32.4) 23(67.6) 出血事件 4.956 0.026 是 103(79.2) 60(58.3) 43(41.7) 否 27(20.8) 22(81.5) 5(18.5) 使用抗生素 4.162 0.014 是 50(38.5) 37(74.0) 13(26.0) 否 80(61.5) 45(56.3) 35(43.7) 使用升血小板药 2.196 0.138 是 57(43.8) 40(70.2) 17(29.8) 否 73(56.2) 42(57.5) 31(42.5) 慢性胃炎 21.047 < 0.001 是 46(35.4) 39(84.8) 7(15.2) 否 84(64.6) 43(51.2) 44(48.8) 脾大 51.268 < 0.001 是 72(55.4) 65(90.3) 7(9.7) 否 58(44.6) 17(29.3) 41(70.7) 心血管疾病 0.03 0.826 是 69(53.1) 44(63.8) 25(36.2) 否 61(46.9) 38(62.3) 23(37.7) 糖尿病 0.744 0.388 是 86(66.2) 52(60.5) 34(39.5) 否 44(46.9) 30(68.2) 14(31.8) 感染 1.609 0.205 是 47(36.2) 33(70.2) 14(29.8) 否 83(63.8) 49(59.0) 34(41.0) T1/min 13.25(5.1) 13.00(7.0) 11.50(6.0) 2.076 0.038 T2/min 40.0(15.0) 40.0(7.0) 37.5(10.0) 2.255 0.024 NLR 1.39(2.82) 1.25(2.56) 1.68(3.19) 1.669 0.095 LMR 5.00(7.52) 5.65(7.19) 4.03(6.47) 2.68 0.007 PLR 9.77(11.24) 11.53(10.98) 6.13(9.67) 3.632 < 0.001 注：T1为取血至开始输血时间间隔，T2为开始输血至输血结束时间间隔。 
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表 2 MDS患者血小板输注疗效影响因素的多因素logistic回归分析
变量 β 显著性 OR(95%CI) 性别 -1.193 0.234 0.303(0.043~2.160) 年龄/岁 0.058 0.143 1.060(0.981~1.145) 输注前PLT/(×109/L) -0.106 0.064 0.900(0.805~1.006) 0~5 对照 6~10 -0.477 0.634 0.620(0.087~4.415) 11~20 -0.853 0.417 0.426(0.054~3.344) >20 -0.628 0.737 0.534(0.014~20.889) 输血小板袋数/袋 -0.168 0.001 0.845(0.763~0.936) 1~5 对照 6~10 -2.153 0.012 0.116(0.022~0.625) 11~15 -2.847 0.023 0.058(0.005~0.676) ≥16 -1.77 0.068 0.170(0.026~1.137) 脾大 否 对照 是 -5.098 0.002 0.036(0.009~0.138) 是否化疗 否 对照 是 -2.428 0.050 0.088(0.008~1.003) 慢性胃炎 否 对照 是 1.319 0.299 3.740(0.031~45.104) 使用抗生素 否 对照 是 -0.968 0.216 0.380(0.082~1.758) 出血事件 否 对照 是 -1.088 0.289 0.337(0.045~2.521) LMR -0.006 0.864 0.994(0.924~1.069) PLR 0.035 0.387 1.036(0.957~1.069) 常量 1.88 0.517 6.552
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表 3 单因素及多因素联合预测模型ROC曲线值
变量 ACU 特异度 灵敏度 约登指数 截断值 脾肿大 0.823 0.793 0.854 0.647 化疗 0.673 0.866 0.479 0.345 输注血小板袋数 0.781 0.683 0.833 0.516 5.5袋 联合预测 0.900 0.854 0.854 0.708 0.596 注：联合预测指将脾肿大、化疗、输注血小板袋数三因素联合预测血小板输注疗效。
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