Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study

Background We previously reported that the “Endothelial Activation and Stress Index” (EASIX; ((creatinine×lactate dehydrogenase)÷thrombocytes)) measured before start of conditioning predicts mortality after allogeneic hematopoietic stem cell transplantation (alloSCT) when used as continuous score. F...

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Main Authors: Axel Benner, Peter Dreger, Grzegorz W Basak, Christian Koenecke, Olaf Penack, Christophe Peczynski, Lucia López Corral, Ivan Moiseev, Hélène Schoemans, Zinaida Peric, Thomas Luft, Simona Sica, Mutlu Arat, Maija Itäla-Remes, Nicolaas P M Schaap, Michal Karas, Ludek Raida, Thomas Schroeder, Elisabetta Metafuni, Tulay Ozcelik, Brenda M Sandmaier, Lambros Kordelas
Format: Article
Language:English
Published: BMJ Publishing Group 2024-01-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/12/1/e007635.full
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author Axel Benner
Peter Dreger
Grzegorz W Basak
Christian Koenecke
Olaf Penack
Christophe Peczynski
Lucia López Corral
Ivan Moiseev
Hélène Schoemans
Zinaida Peric
Thomas Luft
Simona Sica
Mutlu Arat
Maija Itäla-Remes
Nicolaas P M Schaap
Michal Karas
Ludek Raida
Thomas Schroeder
Elisabetta Metafuni
Tulay Ozcelik
Brenda M Sandmaier
Lambros Kordelas
author_facet Axel Benner
Peter Dreger
Grzegorz W Basak
Christian Koenecke
Olaf Penack
Christophe Peczynski
Lucia López Corral
Ivan Moiseev
Hélène Schoemans
Zinaida Peric
Thomas Luft
Simona Sica
Mutlu Arat
Maija Itäla-Remes
Nicolaas P M Schaap
Michal Karas
Ludek Raida
Thomas Schroeder
Elisabetta Metafuni
Tulay Ozcelik
Brenda M Sandmaier
Lambros Kordelas
author_sort Axel Benner
collection DOAJ
description Background We previously reported that the “Endothelial Activation and Stress Index” (EASIX; ((creatinine×lactate dehydrogenase)÷thrombocytes)) measured before start of conditioning predicts mortality after allogeneic hematopoietic stem cell transplantation (alloSCT) when used as continuous score. For broad clinical implementation, a prospectively validated EASIX-pre cut-off is needed that defines a high-risk cohort and is easy to use.Method In the current study, we first performed a retrospective cohort analysis in n=2022 alloSCT recipients and identified an optimal cut-off for predicting non-relapse mortality (NRM) as EASIX-pre=3. For cut-off validation, we conducted a multicenter prospective study with inclusion of n=317 first alloSCTs from peripheral blood stem cell in adult patients with acute leukemia, lymphoma or myelodysplastic syndrome/myeloproliferative neoplasms in the European Society for Blood and Marrow Transplantation network.Results Twenty-three % (n=74) of alloSCT recipients had EASIX-pre ≥3 taken before conditioning. NRM at 2 years was 31.1% in the high EASIX group versus 11.5% in the low EASIX group (p<0.001). Patients with high EASIX-pre also had worse 2 years overall survival (51.6% vs 70.9%; p=0.002). We were able to validate the cut-off and found that EASIX ≥3 was associated with more than twofold increased risk for NRM in multivariate analysis (HR=2.18, 95% CI 1.2 to 3.94; p=0.01). No statistically significant difference could be observed for the incidence of relapse.Conclusions The results of this study provide a prospectively validated standard laboratory biomarker index to estimate the transplant-related mortality risk after alloSCT. EASIX ≥3 taken before conditioning identifies a population of alloSCT recipients who have a more than twofold increased risk of treatment-related mortality.
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series Journal for ImmunoTherapy of Cancer
spelling doaj-art-60017a9b556c4c1eaccc5b562a3da1442025-02-09T21:05:10ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-01-0112110.1136/jitc-2023-007635Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective studyAxel Benner0Peter Dreger1Grzegorz W Basak2Christian Koenecke3Olaf Penack4Christophe Peczynski5Lucia López Corral6Ivan Moiseev7Hélène Schoemans8Zinaida Peric9Thomas Luft10Simona Sica11Mutlu Arat12Maija Itäla-Remes13Nicolaas P M Schaap14Michal Karas15Ludek Raida16Thomas Schroeder17Elisabetta Metafuni18Tulay Ozcelik19Brenda M Sandmaier20Lambros Kordelas21German Cancer Research Centre, Heidelberg, Germany1 Heidelberg University Hospital Department of Hematology Oncology and Rheumatology, Heidelberg, GermanyEBMT Transplant Complications Working Party, Paris, FranceHematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, GermanyDepartment for Haematology, Oncology and Tumorimmunology, Charité Universitätsmedizin Berlin, Berlin, GermanyEBMT Transplant Complications Working Party, Paris, FranceDepartment for Haematology, Hospital Clinico San Carlos, Salamanca, SpainEBMT Transplant Complications Working Party, Paris, FranceEBMT Transplant Complications Working Party, Paris, FranceEBMT Transplant Complications Working Party, Paris, FranceDepartment of Medicine V, University Hospital and Medical Faculty Heidelberg, Heidelberg, Baden-Württemberg, GermanyIstituto di Ematologia, Universita Cattolica S. Cuore, Rome, ItalyFlorence Nightingale Hospital, Hematopoietic SCT Unit, Demiroglu Bilim University Istanbul, Istanbul, TurkeyTurku University Hospital FI, Turku, FinlandDepartment of Hematology, Radboudumc, Nijmegen, The NetherlandsHospital Dept. of Hematology/Oncology, Charles University, Pilsen, Czech RepublicOlomouc University Social Health Institute, Olomouc, Czech RepublicDept. of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, GermanyIstituto di Ematologia, Universita Cattolica S. Cuore, Rome, ItalyFlorence Nightingale Hospital, Hematopoietic SCT Unit, Demiroglu Bilim University Istanbul, Istanbul, TurkeyUniversity of Washington, Seattle, Washington, USADept. of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, GermanyBackground We previously reported that the “Endothelial Activation and Stress Index” (EASIX; ((creatinine×lactate dehydrogenase)÷thrombocytes)) measured before start of conditioning predicts mortality after allogeneic hematopoietic stem cell transplantation (alloSCT) when used as continuous score. For broad clinical implementation, a prospectively validated EASIX-pre cut-off is needed that defines a high-risk cohort and is easy to use.Method In the current study, we first performed a retrospective cohort analysis in n=2022 alloSCT recipients and identified an optimal cut-off for predicting non-relapse mortality (NRM) as EASIX-pre=3. For cut-off validation, we conducted a multicenter prospective study with inclusion of n=317 first alloSCTs from peripheral blood stem cell in adult patients with acute leukemia, lymphoma or myelodysplastic syndrome/myeloproliferative neoplasms in the European Society for Blood and Marrow Transplantation network.Results Twenty-three % (n=74) of alloSCT recipients had EASIX-pre ≥3 taken before conditioning. NRM at 2 years was 31.1% in the high EASIX group versus 11.5% in the low EASIX group (p<0.001). Patients with high EASIX-pre also had worse 2 years overall survival (51.6% vs 70.9%; p=0.002). We were able to validate the cut-off and found that EASIX ≥3 was associated with more than twofold increased risk for NRM in multivariate analysis (HR=2.18, 95% CI 1.2 to 3.94; p=0.01). No statistically significant difference could be observed for the incidence of relapse.Conclusions The results of this study provide a prospectively validated standard laboratory biomarker index to estimate the transplant-related mortality risk after alloSCT. EASIX ≥3 taken before conditioning identifies a population of alloSCT recipients who have a more than twofold increased risk of treatment-related mortality.https://jitc.bmj.com/content/12/1/e007635.full
spellingShingle Axel Benner
Peter Dreger
Grzegorz W Basak
Christian Koenecke
Olaf Penack
Christophe Peczynski
Lucia López Corral
Ivan Moiseev
Hélène Schoemans
Zinaida Peric
Thomas Luft
Simona Sica
Mutlu Arat
Maija Itäla-Remes
Nicolaas P M Schaap
Michal Karas
Ludek Raida
Thomas Schroeder
Elisabetta Metafuni
Tulay Ozcelik
Brenda M Sandmaier
Lambros Kordelas
Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study
Journal for ImmunoTherapy of Cancer
title Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study
title_full Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study
title_fullStr Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study
title_full_unstemmed Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study
title_short Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study
title_sort endothelial activation and stress index easix to predict mortality after allogeneic stem cell transplantation a prospective study
url https://jitc.bmj.com/content/12/1/e007635.full
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