Interleukin-18 and Hematopoietic Recovery after Allogeneic Stem Cell Transplantation

Radujkovic, Aleksandar; Kordelas, Lambros; Bogdanov, Rashit; Müller‐Tidow, Carsten; Beelen, Dietrich; Dreger, Peter; Luft, Thomas

doi:10.3390/cancers12102789

Cited by 8 publications

(5 citation statements)

References 47 publications

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“…In contrast, endothelial markers measured pre-transplant or early post-transplant which are associated with an increased risk of NRM (or TMA as the common clinical end stage of endothelial damage) independent of GVHD can be considered as indicators of an actually injured endothelium associated with already manifest endothelial dysfunction. Examples for this type of markers are ST2 and IL18 [27,68] (Fig. 1/Fig.…”

Section: Endothelial Vulnerability and Endothelial Injurymentioning

confidence: 99%

Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

Luft

Dreger

Radujkovic

2021

Bone Marrow Transplant

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Allogeneic hematopoietic stem cell transplantation (alloSCT) carries the promise of cure for many malignant and non-malignant diseases of the lympho-hematopoietic system. Although outcome has improved considerably since the pioneering Seattle achievements more than 5 decades ago, non-relapse mortality (NRM) remains a major burden of alloSCT. There is increasing evidence that endothelial dysfunction is involved in many of the life-threatening complications of alloSCT, such as sinusoidal obstruction syndrome/venoocclusive disease, transplant-associated thrombotic microangiopathy, and refractory acute graft-versus host disease. This review delineates the role of the endothelium in severe complications after alloSCT and describes the current status of search for biomarkers predicting endothelial complications, including markers of endothelial vulnerability and markers of endothelial injury. Finally, implications of our current understanding of transplant-associated endothelial pathology for prevention and management of complications after alloSCT are discussed.

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Section: Endothelial Vulnerability and Endothelial Injurymentioning

confidence: 99%

Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

Luft

Dreger

Radujkovic

2021

Bone Marrow Transplant

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“…Cytokines associating with EASIX and outcome of post-transplant complications include ANG2, sCD141, ST2 ( 19 , 20 , 29 ), CXCL9 ( 30 ) and IL18 ( 31 , 32 ). Interferon-alpha represents an early but transient immune response to viral infections that appeared deficient in COVID-19 patients ( 33 ).…”

Section: Introductionmentioning

confidence: 99%

EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients

Luft

Wendtner²,

Kosely

et al. 2021

Front. Immunol.

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BackgroundThe coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has evoked a pandemic that challenges public health-care systems worldwide. Endothelial cell dysfunction plays a key role in pathophysiology, and simple prognosticators may help to optimize allocation of limited resources. Endothelial activation and stress index (EASIX) is a validated predictor of endothelial complications and outcome after allogeneic stem cell transplantation. Aim of this study was to test if EASIX could predict life-threatening complications in patients with COVID-19.MethodsSARS-CoV-2-positive, hospitalized patients were enrolled onto a prospective non-interventional register study (n=100). Biomarkers were assessed at hospital admission. Primary endpoint was severe course of disease (mechanical ventilation and/or death, V/D). Results were validated in 126 patients treated in two independent institutions.ResultsEASIX at admission was a strong predictor of severe course of the disease (odds ratio for a two-fold change 3.4, 95%CI 1.8-6.3, p<0.001), time to V/D (hazard ratio (HR) for a two-fold change 2.0, 95%CI 1.5-2.6, p<0.001) as well as survival (HR for a two-fold change 1.7, 95%CI 1.2-2.5, p=0.006). The effect was retained in multivariable analysis adjusting for age, gender, and comorbidities and could be validated in the independent cohort. At hospital admission EASIX correlated with increased suppressor of tumorigenicity-2, soluble thrombomodulin, angiopoietin-2, CXCL8, CXCL9 and interleukin-18, but not interferon-alpha.ConclusionEASIX is a validated predictor of COVID19 outcome and an easy-to-access tool to segregate patients in need for intensive surveillance.

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“…EASIX-pre strongly correlated with IL-18 before conditioning therapy, and our group suggested a direct inhibitory effect of IL-18 on platelet production. 33 , 34 In contrast, CXCL9, CRP, and ST2, although increased in this subgroup of patients with severe cGVHD, were not associated with EASIX-1year, underlining the heterogeneity of endothelial derived serum markers.…”

Section: Discussionmentioning

confidence: 68%

EASIX-1year and late mortality after allogeneic stem cell transplantation

Kordelas,

Terzer,

Gooley

et al. 2023

Blood Advances

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Patients with haematological malignancies who survive the first year after allogeneic stem cell transplantation (alloSCT) without relapse have a substantial risk of non-relapse mortality (NRM), and predictive markers are missing. The Endothelial Activation and Stress Index (EASIX) predicts endothelial complications and NRM early after alloSCT. We hypothesised that EASIX assessed 1 year after alloSCT in disease-free survivors may predict late NRM. Relapse-free survivors at one year after alloSCT were retrospectively studied in two independent cohorts (training cohort: n=610, merged validation cohort: n=852). EASIX determined one year after alloSCT was correlated with overall survival (OS), NRM, and relapse. Serum endothelial and inflammatory markers were measured in the training cohort and correlated with EASIX-1y. EASIX-1year predicted OS and NRM but not relapse risk in both, training and validation cohort in univariable and multivariable Cox regression analyses. Brier score and c-index analyses validated the univariable EASIX effects. There was no significant interaction between EASIX-1year and incidence of chronic GvHD on OS. EASIX-1year predicted outcome irrespective of pre-existing comorbidities. Principal causes of NRM in both, training and validation cohorts were infections with and without GvHD, as well as cardiovascular complications. EASIX-1y correlated with sCD141 and interleukin-18, but not with C-reactive protein, suppressor of tumorigenicity (ST)-2, angiopoietin-2, CXCL9 or CXCL8. EASIX-1year is the first validated predictor of late overall and non-relapse mortality. High-risk patients as defined by EASIX-1year might be considered for intensified surveillance and prophylactic measures.

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Interleukin-18 and Hematopoietic Recovery after Allogeneic Stem Cell Transplantation

Cited by 8 publications

References 47 publications

Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation

EASIX for Prediction of Outcome in Hospitalized SARS-CoV-2 Infected Patients

EASIX-1year and late mortality after allogeneic stem cell transplantation

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