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Development and validation of an early mortality risk model for pediatric hemophagocytic lymphohistiocytosis: a comparison with HScore, PELOD-2, P-MODS, and pSOFA

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Abstract

There has been no severity evaluation model for pediatric patients with hemophagocytic lymphohistiocytosis (HLH) that uses readily available parameters. This study aimed to develop a novel model for predicting the early mortality risk in pediatric patients with HLH using easily obtained parameters whatever etiologic subtype. Patients from one center were divided into training and validation sets for model derivation. The developed model was validated using an independent validation cohort from the second center. The prediction model with nomogram was developed based on logistic regression. The model performance underwent internal and external evaluation and validation using the area under the receiver operating characteristic curve (AUC), calibration curve with 1000 bootstrap resampling, and decision curve analysis (DCA). Model performance was compared with the most prevalent severity evaluation scores, including the PELOD-2, P-MODS, and pSOFA scores. The prediction model included nine variables: glutamic-pyruvic transaminase, albumin, globulin, myohemoglobin, creatine kinase, serum potassium, procalcitonin, serum ferritin, and interval between onset and diagnosis. The AUC of the model for predicting the 28-day mortality was 0.933 and 0.932 in the training and validation sets, respectively. The AUC values of the HScore, PELOD-2, P-MODS and pSOFA were 0.815, 0.745, 0.659 and 0.788, respectively. The DCA of the 28-day mortality prediction exhibited a greater net benefit than the HScore, PELOD-2, P-MODS and pSOFA. Subgroup analyses demonstrated good model performance across HLH subtypes. The novel mortality prediction model in this study can contribute to the rapid assessment of early mortality risk after diagnosis with readily available parameters.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank every colleague in Hunan Provincial Key Laboratory of Pediatric Emergency Medicine for their assistance.

Funding

This study was supported by the Hunan Provincial Natural Science Foundation of China (2023JJ30324, grant to XLu), the Hunan Provincial Science and Technology Department Project (2020SK1014-3, and 2020SK2114, grant to XLu), the Hunan Provincial Key Laboratory of Emergency Medicine for Children (No. 2018TP1028, grant to ZX), the National Natural Science Foundation of China (Young Scientists Fund, No. 82102285, grant to XLi), and the Hunan Provincial Health Commission Project (2020SK50509, grant to DZ). The study sponsors have no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

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Authors and Affiliations

  1. Academy of Pediatrics, University of South China, Changsha, China

    Zhexuan Tang, Minghui Tang & Xuedan Jiang

  2. Pediatric Research Institute of Hunan Province and Pediatric Intensive Care Unit (PICU), Hunan Children’s Hospital, Changsha, China

    Xun Li, Ting Luo, Longlong Xie & Yufan Yang

  3. Hunan Provincial Key Laboratory of Emergency Medicine for Children, Hunan Children’s Hospital, Changsha, China

    Zhexuan Tang, Desheng Zhu, Xun Li, Haipeng Yan, Ting Luo, Longlong Xie, Yufan Yang, Minghui Tang, Xuedan Jiang, Jiaotian Huang, Xinping Zhang, Zhenghui Xiao & Xiulan Lu

  4. Pediatric Intensive Care Unit (PICU), Hunan Children’s Hospital, Changsha, China

    Zhexuan Tang, Desheng Zhu, Haipeng Yan, Minghui Tang, Xuedan Jiang, Jiaotian Huang, Xinping Zhang, Zhenghui Xiao & Xiulan Lu

  5. Pediatric Intensive Care Unit (PICU), The First People’s Hospital of Chenzhou, Chenzhou, China

    Lifang Zhou & Yefei Lei

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  1. Zhexuan Tang
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Contributions

ZT contributed to the study’s conception, analyzed and interpreted the data, and wrote the manuscript. DZ, XL, HY, TL, LX, and YY contributed to the study design, interpreted the data, and revised the manuscript. MT, XJ, JH, XZ, LZ, YL and ZX interpreted the data, and revised the manuscript. XLu designed the study, interpreted the data, and revised the manuscript. All authors read and approved the final manuscript. The corresponding author (XLu) had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Xiulan Lu.

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Ethics statement

The study protocol was reviewed and approved by the Medical Ethics Committee of the Hunan Children's Hospital (HCHLL-2022–123) and The First People's Hospital of Chenzhou (2023140).

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Informed consent was waved by the Medical Ethics Committee of the Hunan Children's Hospital because of the retrospective design. The authors had no access to information that could identify individual participants during and after data collection.

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Not applicable.

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The authors declare no competing interests.

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Tang, Z., Zhu, D., Li, X. et al. Development and validation of an early mortality risk model for pediatric hemophagocytic lymphohistiocytosis: a comparison with HScore, PELOD-2, P-MODS, and pSOFA. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05780-2

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