PMID- 31680001
OWN - NLM
STAT- MEDLINE
DCOM- 20200331
LR  - 20200331
IS  - 2352-3964 (Electronic)
IS  - 2352-3964 (Linking)
VI  - 49
DP  - 2019 Nov
TI  - Interleukin-18 and outcome after allogeneic stem cell transplantation: A 
      retrospective cohort study.
PG  - 202-212
LID - S2352-3964(19)30688-7 [pii]
LID - 10.1016/j.ebiom.2019.10.024 [doi]
AB  - 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.
CI  - Copyright (c) 2019 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Radujkovic, Aleksandar
AU  - Radujkovic A
AD  - Department of Internal Medicine V, University Hospital Heidelberg, Im Neuenheimer 
      Feld 410, 69120 Heidelberg Germany.
FAU - Kordelas, Lambros
AU  - Kordelas L
AD  - Department of Bone Marrow Transplantation, University Hospital Essen, Germany.
FAU - Dai, Hao
AU  - Dai H
AD  - Department of Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, 
      Germany.
FAU - Schult, David
AU  - Schult D
AD  - Department of Internal Medicine V, University Hospital Heidelberg, Im Neuenheimer 
      Feld 410, 69120 Heidelberg Germany.
FAU - Majer-Lauterbach, Joshua
AU  - Majer-Lauterbach J
AD  - Department of Internal Medicine V, University Hospital Heidelberg, Im Neuenheimer 
      Feld 410, 69120 Heidelberg Germany.
FAU - Beelen, Dietrich
AU  - Beelen D
AD  - Department of Bone Marrow Transplantation, University Hospital Essen, Germany.
FAU - Muller-Tidow, Carsten
AU  - Muller-Tidow C
AD  - Department of Internal Medicine V, University Hospital Heidelberg, Im Neuenheimer 
      Feld 410, 69120 Heidelberg Germany.
FAU - Dreger, Peter
AU  - Dreger P
AD  - Department of Internal Medicine V, University Hospital Heidelberg, Im Neuenheimer 
      Feld 410, 69120 Heidelberg Germany.
FAU - Luft, Thomas
AU  - Luft T
AD  - Department of Internal Medicine V, University Hospital Heidelberg, Im Neuenheimer 
      Feld 410, 69120 Heidelberg Germany. Electronic address: 
      thomas.luft@med.uni-heidelberg.de.
LA  - eng
PT  - Journal Article
DEP - 20191101
PL  - Netherlands
TA  - EBioMedicine
JT  - EBioMedicine
JID - 101647039
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Adult
MH  - Case-Control Studies
MH  - Cause of Death
MH  - Female
MH  - Graft vs Host Disease/blood/epidemiology
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Incidence
MH  - Interleukin-18/blood/genetics/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Neutrophils/metabolism
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Reproducibility of Results
MH  - Retrospective Studies
MH  - Transplantation, Homologous
MH  - Treatment Outcome
PMC - PMC6945194
OTO - NOTNLM
OT  - Allogeneic stem cell transplantation
OT  - Interleukin-18
OT  - Mortality
OT  - Outcome
COIS- The authors declare no conflicts of interest.
EDAT- 2019/11/05 06:00
MHDA- 2020/04/01 06:00
PMCR- 2019/11/01
CRDT- 2019/11/05 06:00
PHST- 2019/09/18 00:00 [received]
PHST- 2019/10/07 00:00 [revised]
PHST- 2019/10/14 00:00 [accepted]
PHST- 2019/11/05 06:00 [pubmed]
PHST- 2020/04/01 06:00 [medline]
PHST- 2019/11/05 06:00 [entrez]
PHST- 2019/11/01 00:00 [pmc-release]
AID - S2352-3964(19)30688-7 [pii]
AID - 10.1016/j.ebiom.2019.10.024 [doi]
PST - ppublish
SO  - EBioMedicine. 2019 Nov;49:202-212. doi: 10.1016/j.ebiom.2019.10.024. Epub 2019 
      Nov 1.