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Interleukin-18 and hematopoietic recovery after allogeneic stem cell transplantation

Interleukin-18 (IL-18) is an immunoregulatory cytokine and a context-dependent regulator of hematopoietic stem/progenitor cell (HSPC) quiescence in murine models. In a previous study, high pre-conditioning levels of IL-18 were associated with increased non-relapse mortality (NRM) after allogeneic st...

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Main Authors: Radujković, Aleksandar (Author) , Kordelas, Lambros (Author) , Bogdanov, Rashit (Author) , Müller-Tidow, Carsten (Author) , Beelen, Dietrich W. (Author) , Dreger, Peter (Author) , Luft, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 28 September 2020
In: Cancers
Year: 2020, Volume: 12, Issue: 10
ISSN:2072-6694
DOI:10.3390/cancers12102789
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers12102789
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/12/10/2789
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Author Notes:Aleksandar Radujkovic, Lambros Kordelas, Rashit Bogdanov, Carsten Müller-Tidow, Dietrich W. Beelen, Peter Dreger and Thomas Luft

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520 |a Interleukin-18 (IL-18) is an immunoregulatory cytokine and a context-dependent regulator of hematopoietic stem/progenitor cell (HSPC) quiescence in murine models. In a previous study, high pre-conditioning levels of IL-18 were associated with increased non-relapse mortality (NRM) after allogeneic stem cell transplantation (alloSCT). To investigate the clinical impact of IL-18 status on hematopoietic function, the associations of pre-conditioning and day 0–3 cytokine levels with platelet and neutrophil recovery were analyzed in a training cohort of 714 allografted patients. In adjusted logistic regression analyses, both increasing pre-conditioning and day 0–3 IL-18 levels had a significantly higher adjusted odds ratio (aOR) of delayed platelet and neutrophil recovery on day +28 post-transplant (aOR per two-fold increase: 1.6–2.0). The adverse impact of high pre-conditioning IL-18 on day +28 platelet recovery was verified in an independent cohort of 673 allografted patients (aOR per two-fold increase: 1.8 and 1.7 for total and free IL-18, respectively). In both cohorts, a platelet count ≤20/nL on day +28 was associated with a significantly increased hazard of NRM (hazard ratio 2.13 and 2.94, respectively). Our findings support the hypothesis that elevated peritransplant IL-18 levels affect post-transplant HSPC function and may provide a rationale to explore modulation of IL-18 for improving alloSCT outcomes. 
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