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Genetic and clinical characteristics of primary hemophagocytic lymphohistiocytosis in children

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Abstract

To analyze the genetic variation and prognosis of primary hemophagocytic lymphohistiocytosis (pHLH) in children and the clinical features of isolated central nervous system HLH (CNS-HLH). We retrospectively analyzed the clinical and genetic data of 480 HLH children admitted to our hospital from September 2017 to September 2022. There were 66 patients (13.75%) with pHLH, and the median age was 3.21 years (0.17–12.92 years). Variants in UNC13D (22/66, 33.33%), PRF1 (20/66, 30.30%) and XIAP (11/66, 16.67%) were the most common. More CNS involvement was observed in pHLH patients than in secondary hemophagocytic lymphohistiocytosis (sHLH) patients (50% vs. 25.3%, P = 0.001). Eight pHLH patients had isolated CNS-HLH at onset, which progressed to systemic HLH within 10–30 days to several years. Among them, five patients who underwent hematopoietic stem cell transplantation (HSCT) survived without CNS sequelae, and the three patients who did not undergo HSCT died of disease progression or recurrence. Determination of natural killer (NK) cell cytotoxicity and CD107a levels had low sensitivity and specificity in the diagnosis of pHLH, especially in patients with PRF1 and XIAP mutations. The 3-year overall survival (OS) was significantly lower in pHLH patients than in sHLH patients (74.5% ± 14.7% vs. 89.2% ± 3.53%, P = 0.021) and in patients with CNS involvement than in those without (53.8% ± 26.07% vs. 94.4% ± 10.58%, P = 0.012). There was a significant difference in OS among pHLH patients with different gene variants (P = 0.032); patients with PRF1 variants had poor 3-year OS, and patients with XIAP variants had good 3-year OS (50% ± 28.22% and 100%, respectively). pHLH patients with distinct variants have different prognoses. Isolated CNS-HLH patients are easily misdiagnosed, and HSCT may be beneficial for these patients. Determination of NK cell cytotoxicity and CD107a levels cannot precisely distinguish pHLH from sHLH.

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Acknowledgements

The authors would like to thank: Beijing Municipal Science & Technology Commission (No. Z221100007422054), the Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Municipal Administration (No. XTZD20180202), Beijing research ward project (No. BCRW202101), Funding for Reform and development of Beijing Municipal Health Commission.

Funding

This work was supported by Beijing Municipal Science & Technology Commission (No. Z221100007422054), the Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Municipal Administration (No. XTZD20180202), Beijing research ward project (No. BCRW202101), Funding for Reform and development of Beijing Municipal Health Commission.

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Author notes

  1. Chenzi Zhao and Qing Zhang contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Hematologic Diseases, Hematology Center, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56, Nanlishi Road, Xicheng District, Beijing, 100045, China

    Chenzi Zhao, Qing Zhang, Xiaoxi Zhao & Zhigang Li

  2. Beijing Key Laboratory of Pediatric Hematology Oncology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China

    Rui Zhang, Hongyun Lian & Honghao Ma

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  1. Chenzi Zhao
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Contributions

Zhigang Li: Funding acquisition, Supervision, Data curation, Writing-Reviewing and Editing. Chenzi Zhao: Conceptualization, Methodology, Investigation, oversight, Data curation, Writing-Original draft preparation. Qing Zhang: Conceptualization, Methodology, Investigation, oversight, Data curation. Hongyun Lian: Data curation. Honghao Ma: Data curation. Xiaoxi Zhao: Data curation. Rui Zhang: Data curation.

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Correspondence to Zhigang Li.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board (IRB) of Beijing Children’s Hospital, Capital Medical University (Number:2018-71).

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Zhao, C., Zhang, Q., Zhang, R. et al. Genetic and clinical characteristics of primary hemophagocytic lymphohistiocytosis in children. Ann Hematol 103, 17–28 (2024). https://doi.org/10.1007/s00277-023-05499-6

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