Effects of Different Doses of Rituximab on Immunoglobulin Levels in High-risk Pediatrics with Burkitt’s Lymphoma
Authors: 黄 爽 , Li Ying , Sun Yixin , Peng Yaguang , Jin Ling , Yang Jing , Zhang Yonghong , Wang Xiaoling , Duan Yanlong 
Published: May 2024

Abstract

Background: Studies have confirmed that rituximab can improve the efficacy of BL, but there is a certain effect on the level of immunoglobulin, which will lead to the verification of infection, and the previous study of our center has confirmed that reducing the dose of rituximab (4 doses) can achieve a similar effect to the standard dose of rituximab (6 doses), can it reduce the effect on the level of immunoglobulin? To date, few studies have concentrated on the effects of immunoglobulin (Ig) on Chinese paediatric patients. This study aimed to examine whether there is a variation in the impact of different doses of rituximab on immunoglobulin levels in the high-risk group of children with BL.
Methods: Clinical data of high-risk pediatric patients with BL who were treated in Beijing Children's Hospital (Beijing, China) were retrospectively analysed. Baseline characteristics and serum Ig levels were collected at four distinct time points (t0=pre-chemotherapy, t1=at the end of chemotherapy, t2=6 months post-chemotherapy, t3=12 months post-chemotherapy). Ig levels were measured at various time points before and after treatment within three RTX treatment groups: R0 group (standard chemotherapy without RTX), R6 group (6 doses of RTX + chemotherapy), and R4 group (4 doses of RTX + chemotherapy). The objective was to compare whether differences existed among the three groups.
Results:The results revealed that the study enrolled 300 high-risk BL patients, including 256 boys and 44 girls, distributed across three groups based on RTX dosage: R0 group (n=38), R6 group (n=87), and R4 group (n=175). Median Ig levels were assessed at four time points (t0, t1, t2, t3) for each group. In the R0 group, IgA and IgM levels significantly decreased at t1 compared with t0 (P=0.006 and 0.002, respectively), while were gradually recovered at t2, returning to t0 levels at t3 (P=0.073 and 0.293, respectively). IgG levels exhibited no significant difference between t0 and t1 (P=0.89), reaching their lowest levels at t2 and returning to t0 levels at t3 (P=0.14). In the R4 group, the minimum levels of IgA, IgM, and IgG were identified at t1 (P<0.001, <0.001, and <0.001, respectively), which were gradually recovered at t2, while remained lower than t0 levels at t3 (P<0.001, <0.001, and =0.005, respectively). The R6 group exhibited reduction in IgA and IgM levels at t1, with gradual recovery at t2 and t3, while remained lower than t0 levels (P=0.003 and <0.001, respectively). IgG levels in the R6 group decreased at t1 (P<0.001) and did not return to t0 levels at t3 (P=0.004). In the R4 and R6 groups, it was observed that children with hypogammaglobulinemia pre-RTX were more likely to combine withpersistent hypogammaglobulinemia (PH-Ig) post-RTX. A 1:1 matched comparison between R4 and R6 groups (78 patients each) revealed consistently higher IgA, IgM, and IgG levels in the R4 group at each time point after chemotherapy. Notably, IgA and IgG levels recovered earlier in the R4 group than those in the R6 group (P<0.05).
Conclusion: Children with Burkitt lymphoma in the high-risk group were more likely to complicated hypoimmunoglobulinemia after treatment, and the Ig level of the children in the chemotherapy alone group could recover to the pre-chemotherapy level within 1 year of discontinuation of the drug, while the recovery of Ig level in the rituximb group was longer than 1 year(IgG recovery is the slowest). Children with low Ig levels before chemotherapy are more likely to have low Ig levels after chemotherapy, it is important to monitor Ig levels before and during treatment.