Abstract：
OBJECTIVE: To investigate the incidence, clinical and genetic characteristics of pediatric lymphoma patients of China with inborn errors of immunity (IEI)-related gene mutations, which have not been fully studied.
METHODS: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children\'s Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations.
RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006).
CONCLUSIONS: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.
METHODS: From Jan. 2020 to Mar. 2023, IEI-related genetic mutations were retrospectively explored in 108 children with lymphomas admitted to Beijing Children\'s Hospital by NGS. Genetic rule and clinical characteristics as well as treatment outcomes were compared between patients with or without IEI-related gene mutations.
RESULTS: A total of 17 patients (15.7 %) harbored IEI-associated mutations, including 4 cases with X-linked lymphoproliferative syndrome (XLP), 3 cases had mutations in tumor necrosis factor receptor superfamily 13B (TNFRSF13B), 2 cases with Activated p110 syndrome (APDS). Patients with IEI all had alteration of immunocompetence with decreased levels of immunoglobulin and lymphocyte subsets. Recurrent infection existed in 41.2 % of patients. The 18-month event-free survival (EFS) and the overall response rate (ORR) of patients with IEI are significantly lower than those without IEI (33.86% vs. 73.26 %, p = 0.011; 52.94% vs. 87.91 %, p = 0.002, respectively). In addition, patients with IEI had a higher progression disease (PD) rate of 23.5 % than those without IEI of 4.4 % (p = 0.006).
CONCLUSIONS: The present study demonstrated that IEI-associated lymphomas were much more common than originally appreciated in pediatric lymphomas, and those were insensitive to treatment and more likely to progress or relapse. The genomic analysis and a thorough review of the medical history of IEI can be used to distinguish them from pediatric lymphomas without IEI, which are beneficial for the early diagnosis and direct intervention.
摘要：
目的：调查发病率，中国儿童淋巴瘤患者的临床和遗传特征与先天免疫错误（IEI）相关基因突变，尚未得到充分研究。
方法：从1月起2020年3月2023年，对北京儿童医院收治的108例淋巴瘤患儿进行了IEI相关基因突变的回顾性研究。比较有或没有IEI相关基因突变的患者的遗传规律和临床特征以及治疗结果。
结果：共有17例患者（15.7%）存在IEI相关突变，包括4例X连锁淋巴组织增生综合征(XLP),3例肿瘤坏死因子受体超家族13B（TNFRSF13B）突变，2例伴激活型p110综合征(APDS)。IEI患者的免疫功能均发生改变，免疫球蛋白和淋巴细胞亚群水平降低。41.2%的患者存在反复感染。IEI患者的18个月无事件生存率（EFS）和总缓解率（ORR）明显低于无IEI患者（33.86%vs.73.26%,p=0.011;52.94%vs.87.91%,分别为p=0.002)。此外,IEI患者的疾病进展(PD)发生率为23.5%,高于无IEI患者的4.4%(p=0.006).
结论：本研究表明，IEI相关淋巴瘤比最初在小儿淋巴瘤中更常见，那些对治疗不敏感，更有可能进展或复发。基因组分析和对IEI病史的全面回顾可用于将它们与没有IEI的小儿淋巴瘤区分开来。有利于早期诊断和直接干预。
方法：从1月起2020年3月2023年，对北京儿童医院收治的108例淋巴瘤患儿进行了IEI相关基因突变的回顾性研究。比较有或没有IEI相关基因突变的患者的遗传规律和临床特征以及治疗结果。
结果：共有17例患者（15.7%）存在IEI相关突变，包括4例X连锁淋巴组织增生综合征(XLP),3例肿瘤坏死因子受体超家族13B（TNFRSF13B）突变，2例伴激活型p110综合征(APDS)。IEI患者的免疫功能均发生改变，免疫球蛋白和淋巴细胞亚群水平降低。41.2%的患者存在反复感染。IEI患者的18个月无事件生存率（EFS）和总缓解率（ORR）明显低于无IEI患者（33.86%vs.73.26%,p=0.011;52.94%vs.87.91%,分别为p=0.002)。此外,IEI患者的疾病进展(PD)发生率为23.5%,高于无IEI患者的4.4%(p=0.006).
结论：本研究表明，IEI相关淋巴瘤比最初在小儿淋巴瘤中更常见，那些对治疗不敏感，更有可能进展或复发。基因组分析和对IEI病史的全面回顾可用于将它们与没有IEI的小儿淋巴瘤区分开来。有利于早期诊断和直接干预。
