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, Δκ 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.