Interleukin-18 and outcome after allogeneic stem cell transplantation

• Verfasst von: Radujković, Aleksandar [VerfasserIn]
• Verfasst von: Müller-Tidow, Carsten [VerfasserIn]
• Verfasst von: Dreger, Peter [VerfasserIn]
• Verfasst von: Luft, Thomas [VerfasserIn]
• Verfasst von: Schult, David [VerfasserIn]
• Titel: Interleukin-18 and outcome after allogeneic stem cell transplantation
• Titelzusatz: a retrospective cohort study
• Verf.angabe: Aleksandar Radujkovic, Lambros Kordelas, Hao Dai, David Schult, Joshua Majer-Lauterbach, Dietrich Beelen, Carsten Müller-Tidow, Peter Dreger, Thomas Luft
• E-Jahr: 2019
• Jahr: 1 November 2019
• Umfang: 11 S.
• Fussnoten: Gesehen am 30.01.2020
• Titel Quelle: Enthalten in: EBioMedicine
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 2014
• Jahr Quelle: 2019
• Band/Heft Quelle: 49(2019), Seite 202-212
• ISSN Quelle: 2352-3964
• DOI: doi:10.1016/j.ebiom.2019.10.024
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Allogeneic stem cell transplantation
• Sach-SW: Interleukin-18
• Sach-SW: Mortality
• Sach-SW: Outcome
• K10plus-PPN: 168892647X

Abstract

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.