四君子合剂对急性淋巴细胞白血病维持治疗期儿童及青少年免疫功能影响的随机对照研究

A randomized controlled study of the effects of Sijunzi Mixture on immune function in children and adolescents with acute lymphoblastic leukemia during maintenance therapy

摘要

目的 探讨四君子合剂对急性淋巴细胞白血病（ALL）维持治疗期儿童及青少年免疫功能的影响，评估其作为辅助治疗对稳定体液免疫指标的作用。方法 选取2023年1月至2025年6月广东省人民医院儿童血液科收治的进入维持治疗期的50例1～18岁ALL患者，采用随机数表法分为2组。对照组（ n = 25）接受标准维持化学治疗（化疗）；药物组（ n = 25）在标准维持化疗基础上联合口服四君子合剂，疗程约3个月。于维持治疗开始前1天（基线）及维持治疗满12周时，检测并比较2组患者的血常规（白细胞计数、中性粒细胞计数、血红蛋白水平、血小板计数）、免疫球蛋白（IgG、IgA、IgM）、血清游离轻链（κ、λ）及补体水平；比较体液免疫指标从基线至维持治疗满12周的变化值（Δ值）。同时记录治疗中断（化疗暂停）情况作为探索性临床终点。结果 2组患者的性别、年龄、危险度分层比较差异均无统计学意义（均 P > 0.05）。干预后，2组患者的血常规指标、IgA、IgM、血清游离轻链及补体水平比较差异均无统计学意义（均 P > 0.05）；药物组IgG水平高于对照组（ P = 0.036），关键体液免疫指标的下降幅度[ΔIgG（ P = 0.001）、ΔIgA（ P = 0.005）、ΔIgM（ P = 0.022）、Δκ轻链（ P ＜ 0.001）及Δλ轻链（ P = 0.001）]均小于对照组。效应量分析显示，ΔIgG、ΔIgA、Δ κ轻链及Δλ轻链的效应量 r值为0.45～0.63（中等至大效应），ΔIgM的效应量d值为0.67（中等效应）。药物组的化疗中断发生率低于对照组（16.0% vs 48.0%， P = 0.032）。2组未见明显不良反应。结论 在标准维持化疗基础上联合四君子合剂，能减缓ALL维持治疗期儿童及青少年体液免疫指标的下降速度，降低化疗中断发生率。

Abstract

Objective To investigate the effects of Sijunzi Mixture on immune function in children and adolescents with acute lymphoblastic leukemia (ALL) during maintenance therapy, and to evaluate its role as an adjunctive treatment in stabilizing humoral immune parameters. Methods A total of 50 patients aged 1-18 years with ALL who had entered the maintenance therapy phase and were admitted to the Department of Pediatric Hematology, Guangdong Provincial People’s Hospital, from January 2023 to June 2025 were enrolled. They were divided into two groups using a random number table method. The control group ( n = 25) received standard maintenance chemotherapy, while the medication group ( n = 25) received oral Sijunzi Mixture in addition to standard maintenance chemotherapy for approximately three months. Routine blood parameters, including white blood cell count, neutrophil count, hemoglobin level, and platelet count, as well as immunoglobulins (IgG, IgA, and IgM), serum free light chains (κ and λ), and complement levels were measured and compared between the two groups one day before the start of maintenance therapy (baseline) and after 12 weeks of maintenance therapy. The change values (Δ values) of humoral immune parameters from baseline to week 12 of maintenance therapy were also compared. Treatment interruption, defined as suspension of chemotherapy, was recorded as an exploratory clinical endpoint. Results There were no statistically significant differences between the two groups in gender, age, or risk stratification (all P > 0.05). After the intervention, there were no statistically significant differences between the two groups in routine blood parameters, IgA, IgM, serum free light chains, or complement levels (all P > 0.05). The IgG level in the medication group was higher than that in the control group ( P = 0.036), and the magnitudes of decline in key humoral immune parameters [ΔIgG ( P = 0.001), ΔIgA ( P = 0.005), ΔIgM ( P = 0.022), Δκ light chain ( P ＜ 0.001), and Δλ light chain ( P = 0.001)] were all smaller than those in the control group. Effect size analysis showed that the r values for ΔIgG, ΔIgA, Δ κ light chain, and Δλ light chain ranged from 0.45 to 0.63, indicating medium to large effects, while the d value for ΔIgM was 0.67, indicating a medium effect. The incidence of chemotherapy interruption was lower in the medication group than in the control group (16.0% vs 48.0%, P = 0.032). No obvious adverse reactions were observed in either group. Conclusions The addition of Sijunzi Mixture to standard maintenance chemotherapy can slow the rate of decline in humoral immune parameters and reduce the incidence of chemotherapy interruption in children and adolescents with ALL during maintenance therapy.

关键词

儿童 / 急性淋巴细胞白血病 / 四君子合剂 / 体液免疫 / 随机对照试验

Key words

Children / Acute lymphoblastic leukemia / Sijunzi Mixture / Humoral immunity / Randomized controlled trial

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基金资助

广东省中医药局面上项目(20231010)