Interleukin-18 and outcome after allogeneic stem cell transplantation: a retrospective cohort study
Background - Interleukin-18 (IL-18) is involved in endothelial activation and dysfunction, and in the pathogenesis and severity of acute graft-versus-host disease (aGVHD). Its relevance for patient outcome after allogeneic stem cell transplantation (alloSCT) has not yet been comprehensively addresse...
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| Hauptverfasser: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
1 November 2019
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| In: |
EBioMedicine
Year: 2019, Jahrgang: 49, Pages: 202-212 |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2019.10.024 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1016/j.ebiom.2019.10.024 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S2352396419306887 
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| Verfasserangaben: | Aleksandar Radujkovic, Lambros Kordelas, Hao Dai, David Schult, Joshua Majer-Lauterbach, Dietrich Beelen, Carsten Müller-Tidow, Peter Dreger, Thomas Luft |
| Zusammenfassung: | Background - Interleukin-18 (IL-18) is involved in endothelial activation and dysfunction, and in the pathogenesis and severity of acute graft-versus-host disease (aGVHD). Its relevance for patient outcome after allogeneic stem cell transplantation (alloSCT) has not yet been comprehensively addressed. - Methods - Pre-transplant serum levels of free IL-18 were retrospectively assessed in a cohort of 589 patients (training cohort). Results were validated in 688 patients allografted in a different centre. The primary endpoint was overall survival (OS). Secondary endpoints included incidences of non-relapse mortality (NRM), relapse, and aGVHD. - Findings - In the training cohort, higher pre-transplant levels of free IL-18 were significantly associated with worse OS (hazard ratio [HR] per 1-log2 increase, 1.25, P=0.008) in multivariable models. This was due to a higher hazard of NRM (HR per 1-log2 increase, 1.39, P=0.001), rather than relapse. The associations of pre-transplant free IL-18 with higher NRM (HR per 1-log2 increase, 1.24, P=0.02) and shorter OS (HR per 1-log2 increase, 1.22, P=0.006) were confirmed in the validation cohort. In both cohorts, the correlations of higher pre-transplant free IL-18 serum levels with increased NRM and worse OS were mainly driven by fatal infectious complications. No associations with incidence of aGVHD were observed. - Interpretation - Higher pre-transplant levels of free IL-18 were associated with non-relapse and overall mortality after alloSCT. Our results may provide a rationale for prospective studies evaluating IL-18 status and inhibition of IL-18 activity in patients undergoing allografting. |
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| Beschreibung: | Gesehen am 30.01.2020 |
| Beschreibung: | Online Resource |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2019.10.024 |