Huang Shuang, Li Ying, Sun Yixin, Peng Yaguang, Jin Ling, Yang Jing, Zhang Yonghong, Wang Xiaoling, Duan Yanlong
Medical Oncology Department, Pediatric Oncology Center, Beijing Children's Hospital, Beijing Key Laboratory of Pediatric Hematology Oncology, Key Laboratory of Major Disease in Children, Capital Medical University, National Center for Children's Health, Ministry of Education, Beijing, 100045, China.
Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
Ann Hematol. 2024 Dec;103(12):5807-5816. doi: 10.1007/s00277-024-06059-2. Epub 2024 Nov 7.
Studies have confirmed that rituximab (RTX) 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 RTX (4 doses) can achieve a similar effect to the standard dose of RTX (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 RTX on immunoglobulin levels in the high-risk group of children with BL. 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. 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 with persistent 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). Burkitt lymphoma in the high-risk group were more likely to complicated hypoimmunoglobulinemia after treatment, it is important to monitor Ig levels before and during treatment, and to inform replacement therapy for Ig. Compared with standard chemotherapy group, the RTX group had a longer time of low Ig and a slower recovery, reducing the dosage of rituximab can improve the recovery of IgA and IgG levels.
研究证实,利妥昔单抗(RTX)可提高伯基特淋巴瘤(BL)的疗效,但对免疫球蛋白水平有一定影响,会导致感染风险增加,且本中心之前的研究证实,降低RTX剂量(4剂)可达到与标准剂量RTX(6剂)相似的效果,那么它是否能降低对免疫球蛋白水平的影响呢?迄今为止,很少有研究关注免疫球蛋白(Ig)对中国儿科患者的影响。本研究旨在探讨不同剂量的RTX对BL高危儿童免疫球蛋白水平的影响是否存在差异。对在北京儿童医院(中国北京)接受治疗的BL高危儿科患者的临床资料进行回顾性分析。在四个不同时间点(t0 = 化疗前,t1 = 化疗结束时,t2 = 化疗后6个月,t3 = 化疗后12个月)收集基线特征和血清Ig水平。在三个RTX治疗组治疗前后的不同时间点测量Ig水平:R0组(无RTX的标准化疗)、R6组(6剂RTX + 化疗)和R4组(4剂RTX + 化疗)。目的是比较三组之间是否存在差异。结果显示,该研究纳入了300例高危BL患者,其中包括256名男孩和44名女孩,根据RTX剂量分为三组:R0组(n = 38)、R6组(n = 87)和R4组(n = 175)。对每组在四个时间点(t0、t1、t2、t3)评估Ig水平中位数。在R0组中,与t0相比,t1时IgA和IgM水平显著降低(分别为P = 0.006和0.002),而在t2时逐渐恢复,t3时恢复到t0水平(分别为P = 0.073和0.293)。t0和t1之间IgG水平无显著差异(P = 0.89),在t2时达到最低水平,t3时恢复到t0水平(P = 0.14)。在R4组中,IgA、IgM和IgG的最低水平在t1时出现(分别为P < 0.001、< 0.001和< 0.001),在t2时逐渐恢复,但在t3时仍低于t0水平(分别为P < 0.001、< 0.001和 = 0.005)。R6组在t1时IgA和IgM水平降低,在t2和t3时逐渐恢复,但仍低于t0水平(分别为P = 0.003和< 0.001)。R6组IgG水平在t1时降低(P < 0.001),在t3时未恢复到t0水平(P = 0.004)。在R4组和R6组中,观察到RTX治疗前低丙种球蛋白血症的儿童更有可能在RTX治疗后合并持续性低丙种球蛋白血症(PH-Ig)。R4组和R6组(每组78例患者)进行1:1匹配比较显示,化疗后每个时间点R4组的IgA、IgM和IgG水平始终较高。值得注意的是,R4组的IgA和IgG水平比R6组恢复得更早(P < 0.05)。高危组的伯基特淋巴瘤治疗后更易合并低免疫球蛋白血症,治疗前和治疗期间监测Ig水平并告知Ig替代治疗很重要。与标准化疗组相比,RTX组低Ig时间更长且恢复较慢,降低利妥昔单抗剂量可改善IgA和IgG水平的恢复。