Department of Clinical Immunology and Allergology, St. Anne's University Hospital in Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University Brno, Czech Republic.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2024 Jun;168(2):167-176. doi: 10.5507/bp.2023.021. Epub 2023 May 23.
BACKGROUND: RTX, an anti-CD20 monoclonal antibody, added to chemotherapy has proven to be effective in children and adolescents with high-grade, high-risk and matured non-Hodgkin lymphoma. RTX leads to prompt CD19+ B lymphocyte depletion. However, despite preserved immunoglobulin production by long-lived plasmablasts after treatment, patients remain at risk of prolonged hypogammaglobulinemia. Further, there are few general guidelines for immunology laboratories and clinical feature monitoring after B cell-targeted therapies. The aim of this paper is to describe B cell reconstitution and immunoglobulin levels after pediatric B-NHL protocols, that included a single RTX dose and to review the literature. METHODS: A retrospective single-center study on the impact of a single RTX dose included in a chemotherapeutic pediatric B Non-Hodgkin Lymphoma (B-NHL) treatment protocols. Immunology laboratory and clinical features were evaluated over an eight hundred days follow-up (FU) period, after completing B-NHL treatment. RESULTS: Nineteen patients (fifteen Burkitt lymphoma, three Diffuse large B cell lymphoma, and one Marginal zone B cell lymphoma) fulfilled the inclusion criteria. Initiation of B cell subset reconstitution occurred a median of three months after B-NHL treatment. Naïve and transitional B cells declined over the FU in contrast to the marginal zone and the switched memory B cell increase. The percentage of patients with IgG, IgA, and IgM hypogammaglobulinemia declined consistently over the FU. Prolonged IgG hypogammaglobulinemia was detectable in 9%, IgM in 13%, and IgA in 25%. All revaccinated patients responded to protein-based vaccines by specific IgG antibody production increase. Following antibiotic prophylaxes, none of the patients with hypogammaglobulinemia manifested with either a severe or opportunistic infection course. CONCLUSION: The addition of a single RTX dose to the chemotherapeutic treatment protocols was not shown to increase the risk of developing secondary antibody deficiency in B-NHL pediatric patients. Observed prolonged hypogammaglobulinemia remained clinically silent. However interdisciplinary agreement on regular long-term immunology FU after anti-CD20 agent treatment is required.
背景：RTX，一种抗 CD20 的单克隆抗体，与化疗联合使用已被证明对儿童和青少年的高级别、高危和成熟的非霍奇金淋巴瘤有效。RTX 导致 CD19+B 淋巴细胞迅速耗竭。然而，尽管在治疗后长寿浆母细胞仍然保持免疫球蛋白的产生，患者仍然存在长期低丙种球蛋白血症的风险。此外，针对 B 细胞靶向治疗后免疫学实验室和临床特征监测，目前几乎没有一般的指南。本文的目的是描述包含单次 RTX 剂量的儿科 B-NHL 方案后 B 细胞重建和免疫球蛋白水平，并回顾文献。
方法：对包括单次 RTX 剂量的儿科 B 型非霍奇金淋巴瘤（B-NHL）治疗方案中的单次 RTX 剂量的影响进行回顾性单中心研究。在完成 B-NHL 治疗后，对 800 天的随访（FU）期间的免疫学实验室和临床特征进行评估。
结果：19 名患者（15 名伯基特淋巴瘤，3 名弥漫性大 B 细胞淋巴瘤，1 名边缘区 B 细胞淋巴瘤）符合纳入标准。B-NHL 治疗后，B 细胞亚群重建的开始中位数发生在三个月后。与 FU 期间幼稚和过渡 B 细胞减少相反，边缘区和转换记忆 B 细胞增加。IgG、IgA 和 IgM 低丙种球蛋白血症的患者百分比在 FU 期间持续下降。9%的患者可检测到 IgG 持续低丙种球蛋白血症，13%的患者 IgM 持续低丙种球蛋白血症，25%的患者 IgA 持续低丙种球蛋白血症。所有接受疫苗复种的患者均通过特异性 IgG 抗体产生增加来应答蛋白疫苗。在接受抗生素预防治疗后，低丙种球蛋白血症的患者均未出现严重或机会性感染。
结论：在儿科 B-NHL 患者的化疗治疗方案中添加单次 RTX 剂量并未增加发生继发性抗体缺陷的风险。观察到的持续低丙种球蛋白血症在临床上仍保持沉默。然而，需要在使用抗 CD20 药物治疗后，对定期的长期免疫学 FU 达成跨学科共识。
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