益气养血方联合西药治疗非老年成人再生障碍性贫血疗效预测因素分析

Analysis of Predictive Factors for Efficacy of Yiqi Yangxue Prescription Combined with Western Medicine in Treatment of Aplastic Anemia in Non-elderly Adults

目的:探讨益气养血方联合西药治疗非老年成人再生障碍性贫血(AA)患者疗效的预测因素,为中医益气养血法联合西药治疗非老年成人AA提供预后参考。方法:回顾性分析2018年9月至2021年3月就诊于中国中医科学院西苑医院等19家医院并采用益气养血方联合西药治疗的非老年成人AA患者的临床资料,根据治疗6个月的疗效评价结果分为有效组和无效组,分析两组患者在性别、年龄、疾病分型[非重型再障(NSAA)/重型再障(SAA)]、病程、家族史、合并症、药物过敏史、基线血常规[包括血红蛋白(HGB)、白细胞(WBC)、中性粒细胞(ANC)、血小板(PLT)及网织红细胞(Ret)]、T淋巴细胞亚群、骨髓有核细胞增生程度、T-bet及GATA-3基因指标上的差异。结果:共纳入101例非老年成人AA患者,有效组81例,无效组20例。与无效组比较,有效组无药物过敏史患者占比更高(P<0.05);两组患者在身高、体质量、性别、年龄、分型、病程、家族史、合并症方面差异均无统计学意义。与无效组比较,有效组患者治疗前ANC、PLT水平更高(P<0.05),有效组ANC≥1.6×10^(9)个/L、PLT≥25×10^(9)个/L的患者占比更高(P<0.05,P<0.01);两组患者在WBC、HGB、Ret基线水平上无显著统计学差异。有效组患者治疗前CD3^(+)HLA-DR^(+)T细胞水平明显高于无效组(P<0.05),两组患者治疗前CD3^(+)CD19^(-)T细胞、CD4^(+)T细胞、CD8^(+)T细胞、Th1细胞、Th2细胞、CD3^(+)CD25^(+)T细胞水平差异均无统计学意义。有效组患者治疗前骨髓有核细胞增生活跃患者占比明显高于无效组,增生减低、极度减低患者的占比明显低于无效组(P<0.05)。两组患者治疗前T-bet、GATA-3基因表达水平差异均无统计学意义。多因素二元Logistic回归分析显示,治疗前ANC水平及药物过敏史是疗效的独立影响因素(P<0.05,P<0.01),其他指标均不是疗效的影响因素。应用ROC曲线分析治疗前ANC水平对益气养血方联合西药治疗非老年成人AA的预测价值,曲线下面积为0.679(P<0.05),以1.595×10^(9)个/L为临界值,灵敏度为0.42,特异度为0.95。结论:药物过敏史、治疗前ANC、PLT、CD3^(+)HLA-DR+T细胞水平、骨髓有核细胞增生程度是益气养血方联合西药治疗非老年成人AA患者疗效的预测因素;无药物过敏史,治疗前ANC、PLT水平更高,尤其是ANC≥1.6×10^(9)个/L、PLT≥25×10^(9)个/L及治疗前CD3^(+)HLADR^(+)T细胞水平更高,骨髓有核细胞增生更为活跃的非老年成人AA患者运用益气养血方联合西药治疗更易起效。

Objective:To explore the predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating aplastic anemia(AA)in non-elderly adults,so as to provide a reference for predicting the prognosis of this therapy.Method:A retrospective study was conducted with the clinical data of non-elderly adult AA patients who visited 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 and were treated with Yiqi Yangxue Prescription combined with western medicine.According to the efficacy evaluation results at the 6th month of treatment,the patients were assigned into effective and ineffective groups.The two groups were compared in terms of the gender,age,disease classification[non-severe aplastic anemia(NSAA)/severe aplastic anemia(SAA)],course of disease,family history,complications,history of drug allergy,baseline blood routine examination[hemoglobin(HGB),white blood cell(WBC),neutrophil(ANC),platelet(PLT),and reticulocyte(Ret)],T lymphocyte subsets,degree of proliferation of nucleated cells in bone marrow,and expression of T-bet and GATA-3.Result:A total of 101 non-elderly adult AA patients were enrolled in this study,including 81 in the effective group and 20 in the ineffective group.The effective group had a higher proportion of the patients without a history of drug allergy than the ineffective group(P<0.05).The body height,body weight,gender,age,disease classification,course of disease,family history,and complications showed no significant differences between two groups.The effective group had higher levels of ANC and PLT before treatment(P<0.05)and higher proportion of patients with ANC≥1.6×10^(9)/L and PLT≥25×10^(9)/L(P<0.05,P<0.01)than the ineffective group.The baseline levels of WBC,HGB,and Ret showed no significant statistical differences between two groups.The levels of CD3^(+)HLA-DR^(+)T cells in the effective group before treatment was higher than that in the ineffective group(P<0.05).The levels of CD3^(+)CD19^(-)T cells,CD4^(+)T cells,CD8^(+)T cells,Th1 cells,Th2 cells,and CD3^(+)CD25^(+)T cells showed no significant statistical differences between two groups before treatment.The proportion of patients with active bone marrow nucleated cells proliferation in the effective group before treatment were significantly higher than that in the ineffective group,while the proportion of patients with reduced or extremely reduced proliferation were significantly lower than that in the ineffective group(P<0.05).The expression levels of T-bet and GATA-3 genes had no significant differences between two groups before treatment. The multivariate binary logistic regression analysis showed that the ANC level before treatment and history of drug allergy were independent influencing factors for efficacy (P<0.05,P<0.01), while other indicators were not influencing factors for efficacy. The receiver operating characteristic (ROC) curve was applied to analyze the predictive value of the ANC level before treatment in the treatment of AA in non-elderly adults with Yiqi Yangxue prescription combined with western medicine. The area under the curve was 0.679 (P<0.05), with the critical value of 1.595×10^(9)/L, the sensitivity of 0.42, and the specificity of 0.95. Conclusion:The history of drug allergy, pre-treatment ANC, PLT, CD3^(+)HLA-DR^(+) T cell levels, and proliferation of nucleated cells in bone marrow before treatment are predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating AA in non-elderly adults. This therapy tends to be more effective for the patients with no history of drug allergy, higher ANC and PLT levels before treatment, especially those with ANC≥1.6×10^(9)/L, PLT≥25×10^(9)/L, and higher CD3^(+) HLA-DR^(+)T cell levels and the more active proliferation of nucleated cells in bone marrow before treatment.