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Pre-transplant inflammation and its associations with acute GvHD and mortality in pediatric allogeneic hematopoietic stem cell transplantation patients

Bone Marrow Transplantation (2025)Cite this article

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Abstract

In this explorative study we aimed to identify inflammatory serum proteins measured before allogeneic hematopoietic stem cell transplantation (HSCT) that are associated with acute Graft-versus-Host Disease (aGvHD) and mortality in pediatric HSCT recipients. We measured 28 inflammatory serum proteins in 384 pediatric patients (2010–2022) with malignant (30%) and non-malignant (70%) indications for allogeneic HSCT. A sample before the start of the conditioning (T1) was included, as well as a sample on the day of HSCT (T2). For patients who developed aGvHD we also included a sample at the time of diagnosis, before initiation of systemic treatment (TP-GvHD). Associations with aGvHD, steroid-refractory aGvHD, non-relapse mortality (NRM) and overall survival (OS) were analyzed using robust (cause-specific) Cox models. At T1, TNFR1, sIL-2Rα and TNFR2 were among the most strongly associated proteins for the development of aGvHD. Multiple inflammatory proteins, such as CXCL16, TNFR1 and SCF at T1 were highly associated with NRM and OS. At TP-GvHD, ST2 levels were significantly associated with the development of steroid-refractory aGvHD and NRM. This study shows that inflammatory serum protein levels before HSCT are associated with aGvHD and mortality and lays the groundwork for further validation and use in risk-adapted therapy for pediatric HSCT recipients.

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Fig. 1: Explorative analysis of inflammatory proteins at T1.
Fig. 2: Associations of inflammatory serum proteins with clinical outcomes.
Fig. 3: Clinical outcomes stratified by TNFR1 levels.
Fig. 4: Inflammatory serum protein levels in response to the conditioning regimen.
Fig. 5: Associations of inflammatory serum proteins with SR-aGvHD.

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Data availability

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

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Acknowledgements

The authors would like to acknowledge all patients and their families as well as the clinical staff involved in the care of HSCT pediatric patients at the Willem-Alexander Children’s Hospital, Leiden.

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Authors and Affiliations

  1. Willem-Alexander Children’s Hospital, Department of Pediatrics, Pediatric Stem Cell Transplantation unit and Laboratory of Pediatric Immunology, Leiden University Medical Center, Leiden, The Netherlands

    Anne B. Verbeek, Erik G. J. von Asmuth, Anja M. Jansen-Hoogendijk, Marco W. Schilham, Arjan C. Lankester, Gertjan Lugthart, Alexander B. Mohseny & Emilie P. Buddingh

  2. Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands

    Erik B. van den Akker

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Contributions

ABV was responsible for study design, literature review, clinical data collection, data cleaning and statistical analysis, interpretation of results and drafting of the manuscript. EGJA assisted with study design, statistical analysis, and interpretation. EBA provided expert advice on data cleaning and statistical analysis, and interpretation of results. AMJH performed all laboratory tests and collected and cleaned the laboratory data. MWS provided expert advice on study design and laboratory data collection. ACL, GL and ABM were involved in study design and interpretation of results. EPB was responsible for study design, interpretation of results and supervised the research. All authors contributed to writing the manuscript.

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Correspondence to Anne B. Verbeek or Emilie P. Buddingh.

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Verbeek, A.B., von Asmuth, E.G.J., van den Akker, E.B. et al. Pre-transplant inflammation and its associations with acute GvHD and mortality in pediatric allogeneic hematopoietic stem cell transplantation patients. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02583-5

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