Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study

Chao Yang; Nan Li; Meng Zhang; Shuang Huang; Ling Jin; Shu-Guang Liu; Chun-Ju Zhou; Zhi-Gang Li; Yan-Long Duan

doi:10.1016/j.jped.2024.02.002

Inborn errors of immunity and its clinical significance in children with lymphoma in China: a single-center study

J Pediatr (Rio J). 2024 Mar 25:S0021-7557(24)00029-9. doi: 10.1016/j.jped.2024.02.002. Online ahead of print.

Authors

Chao Yang¹, Nan Li², Meng Zhang², Shuang Huang², Ling Jin², Shu-Guang Liu¹, Chun-Ju Zhou³, Zhi-Gang Li⁴, Yan-Long Duan⁵

Affiliations

¹ Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
² Medical Oncology Department, Pediatric Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China.
³ Department of Pathology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China.
⁴ Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China. Electronic address: ericlzg@hotmail.com.
⁵ Medical Oncology Department, Pediatric Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing, China. Electronic address: duanyanlong@hotmail.com.

PMID: 38547930
DOI: 10.1016/j.jped.2024.02.002

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.

Method: 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).

Conclusion: 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.

Keywords: China; Clinical features; Genes; Inborn errors of immunity; Mutation; Pediatric lymphoma.