Interleukin-18 and hematopoietic recovery after allogeneic stem cell transplantation

• Verfasst von: Radujković, Aleksandar [VerfasserIn]
• Verfasst von: Kordelas, Lambros [VerfasserIn]
• Verfasst von: Bogdanov, Rashit [VerfasserIn]
• Verfasst von: Müller-Tidow, Carsten [VerfasserIn]
• Verfasst von: Beelen, Dietrich W. [VerfasserIn]
• Verfasst von: Dreger, Peter [VerfasserIn]
• Verfasst von: Luft, Thomas [VerfasserIn]
• Titel: Interleukin-18 and hematopoietic recovery after allogeneic stem cell transplantation
• Verf.angabe: Aleksandar Radujkovic, Lambros Kordelas, Rashit Bogdanov, Carsten Müller-Tidow, Dietrich W. Beelen, Peter Dreger and Thomas Luft
• E-Jahr: 2020
• Jahr: 28 September 2020
• Umfang: 20 S.
• Fussnoten: Gesehen am 23.11.2020
• Titel Quelle: Enthalten in: Cancers
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2020
• Band/Heft Quelle: 12(2020,10) Artikel-Nummer 2789, 20 Seiten
• ISSN Quelle: 2072-6694
• DOI: doi:10.3390/cancers12102789
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: allogeneic stem cell transplantation
• Sach-SW: hematopoietic recovery
• Sach-SW: interleukin-18
• Sach-SW: non-relapse mortality
• K10plus-PPN: 1740364694

Abstract

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.