Validation of the revised 2022 European LeukemiaNet risk stratification in adult patients with acute myeloid leukemia

Abstract: In 2022, the European LeukemiaNet (ELN) risk stratification for patients with acute myeloid leukemia (AML) has been updated. We aimed to validate the prognostic value of the 2022 ELN classification (ELN22) by evaluating 1570 patients with newly diagnosed AML (median age, 56 years) treated...

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Main Authors: Leo Ruhnke, Marius Bill, Sven Zukunft, Jan-Niklas Eckardt, Silvia Schäfer, Sebastian Stasik, Maher Hanoun, Thomas Schroeder, Lars Fransecky, Björn Steffen, Stefan W. Krause, Sebastian Scholl, Andreas Hochhaus, Tim Sauer, Sabrina Kraus, Kerstin Schäfer-Eckart, Martin Kaufmann, Edgar Jost, Tim Brümmendorf, Christoph Schliemann, Jan-Henrik Mikesch, Utz Krug, Mathias Hänel, Anke Morgner, Markus Schaich, Andreas Neubauer, Roland Repp, Dirk Niemann, Ruth Seggewiss-Bernhardt, Achim Meinhardt, Johannes Kullmer, Ulrich Kaiser, Wolfgang Blau, Alexander Kiani, Götz Ulrich Grigoleit, Aristoteles Giagounidis, Alexander A. Wurm, Heidi Altmann, Jan Moritz Middeke, Johannes Schetelig, Carsten Müller-Tidow, Friedrich Stölzel, Claudia D. Baldus, Uwe Platzbecker, Hubert Serve, Martin Bornhäuser, Christian Thiede, Christoph Röllig
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Blood Advances
Online Access:http://www.sciencedirect.com/science/article/pii/S2473952924006438
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author Leo Ruhnke
Marius Bill
Sven Zukunft
Jan-Niklas Eckardt
Silvia Schäfer
Sebastian Stasik
Maher Hanoun
Thomas Schroeder
Lars Fransecky
Björn Steffen
Stefan W. Krause
Sebastian Scholl
Andreas Hochhaus
Tim Sauer
Sabrina Kraus
Kerstin Schäfer-Eckart
Martin Kaufmann
Edgar Jost
Tim Brümmendorf
Christoph Schliemann
Jan-Henrik Mikesch
Utz Krug
Mathias Hänel
Anke Morgner
Markus Schaich
Andreas Neubauer
Roland Repp
Dirk Niemann
Ruth Seggewiss-Bernhardt
Achim Meinhardt
Johannes Kullmer
Ulrich Kaiser
Wolfgang Blau
Alexander Kiani
Götz Ulrich Grigoleit
Aristoteles Giagounidis
Alexander A. Wurm
Heidi Altmann
Jan Moritz Middeke
Johannes Schetelig
Carsten Müller-Tidow
Friedrich Stölzel
Claudia D. Baldus
Uwe Platzbecker
Hubert Serve
Martin Bornhäuser
Christian Thiede
Christoph Röllig
author_facet Leo Ruhnke
Marius Bill
Sven Zukunft
Jan-Niklas Eckardt
Silvia Schäfer
Sebastian Stasik
Maher Hanoun
Thomas Schroeder
Lars Fransecky
Björn Steffen
Stefan W. Krause
Sebastian Scholl
Andreas Hochhaus
Tim Sauer
Sabrina Kraus
Kerstin Schäfer-Eckart
Martin Kaufmann
Edgar Jost
Tim Brümmendorf
Christoph Schliemann
Jan-Henrik Mikesch
Utz Krug
Mathias Hänel
Anke Morgner
Markus Schaich
Andreas Neubauer
Roland Repp
Dirk Niemann
Ruth Seggewiss-Bernhardt
Achim Meinhardt
Johannes Kullmer
Ulrich Kaiser
Wolfgang Blau
Alexander Kiani
Götz Ulrich Grigoleit
Aristoteles Giagounidis
Alexander A. Wurm
Heidi Altmann
Jan Moritz Middeke
Johannes Schetelig
Carsten Müller-Tidow
Friedrich Stölzel
Claudia D. Baldus
Uwe Platzbecker
Hubert Serve
Martin Bornhäuser
Christian Thiede
Christoph Röllig
author_sort Leo Ruhnke
collection DOAJ
description Abstract: In 2022, the European LeukemiaNet (ELN) risk stratification for patients with acute myeloid leukemia (AML) has been updated. We aimed to validate the prognostic value of the 2022 ELN classification (ELN22) by evaluating 1570 patients with newly diagnosed AML (median age, 56 years) treated with cytarabine-based intensive chemotherapy regimens. Compared with 2017 ELN classification (ELN17), which allocated 595 (38%), 413 (26%), and 562 patients (36%) to the favorable-, intermediate-, and adverse-risk categories, ELN22 classified 575 (37%), 410 (26%), and 585 patients (37%) as favorable, intermediate, and adverse risk, respectively. Risk group allocation was revised in 340 patients (22%). Most patients were reclassified into the ELN22 intermediate- or ELN22 adverse-risk group. The allocation of patients according to the ELN22 risk categories resulted in a significantly distinct event-free survival (EFS), relapse-free survival, and overall survival (OS). Compared with ELN17, reallocation according to the ELN22 recommendations resulted in a significantly improved prognostic discrimination for OS (3-year area under the curve, 0.71 vs 0.67). In patients with ELN22 favorable-risk AML, co-occurring myelodysplasia-related (MR) gene mutations did not significantly affect outcomes. Within the ELN22 adverse-risk group, we observed marked survival differences across mutational groups (5-year OS rate of 21% and 3% in patients with MR gene mutations and TP53 mutations, respectively). In patients harboring MR gene mutations, EZH2-, STAG2-, and ZRSR2-mutated patients showed an intermediate-like OS. In patients with secondary AML and those who underwent allogeneic hematopoietic cell transplantation, EFS and OS significantly differed between ELN22 risk groups, whereas the prognostic abilities of ELN17 and ELN22 classifications were similar. In conclusion, ELN22 improves prognostic discrimination in a large cohort of intensively treated patients with AML. Given the heterogeneous outcome in patients with MR gene alterations, ranging between those of intermediate and adverse risk patients, we suggest re-evaluation of risk allocation in these patients.
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spelling doaj-art-daabb8a8540349dc9db2f5d80e23fb5b2025-08-20T02:07:40ZengElsevierBlood Advances2473-95292025-03-01961392140410.1182/bloodadvances.2024013304Validation of the revised 2022 European LeukemiaNet risk stratification in adult patients with acute myeloid leukemiaLeo Ruhnke0Marius Bill1Sven Zukunft2Jan-Niklas Eckardt3Silvia Schäfer4Sebastian Stasik5Maher Hanoun6Thomas Schroeder7Lars Fransecky8Björn Steffen9Stefan W. Krause10Sebastian Scholl11Andreas Hochhaus12Tim Sauer13Sabrina Kraus14Kerstin Schäfer-Eckart15Martin Kaufmann16Edgar Jost17Tim Brümmendorf18Christoph Schliemann19Jan-Henrik Mikesch20Utz Krug21Mathias Hänel22Anke Morgner23Markus Schaich24Andreas Neubauer25Roland Repp26Dirk Niemann27Ruth Seggewiss-Bernhardt28Achim Meinhardt29Johannes Kullmer30Ulrich Kaiser31Wolfgang Blau32Alexander Kiani33Götz Ulrich Grigoleit34Aristoteles Giagounidis35Alexander A. Wurm36Heidi Altmann37Jan Moritz Middeke38Johannes Schetelig39Carsten Müller-Tidow40Friedrich Stölzel41Claudia D. Baldus42Uwe Platzbecker43Hubert Serve44Martin Bornhäuser45Christian Thiede46Christoph Röllig47Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; Correspondence: Leo Ruhnke, Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Fetscherstraße 74, 01309 Dresden, Germany;Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; Mildred Scheel Early Career Center, Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; National Center for Tumor Diseases Dresden (NCT/UCC), Medical Faculty and University Hospital Dresden, Technical University Dresden, Dresden, Germany; German Cancer Consortium (DKTK), Dresden, GermanyDepartment of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, GermanyDepartment of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; Mildred Scheel Early Career Center, Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; Else Kröner Fresenius Center for Digital Health, Technical University Dresden, Dresden, GermanyMildred Scheel Early Career Center, Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; National Center for Tumor Diseases Dresden (NCT/UCC), Medical Faculty and University Hospital Dresden, Technical University Dresden, Dresden, GermanyDepartment of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, GermanyDepartment of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, GermanyDepartment of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, GermanyDepartment of Internal Medicine II, University Hospital Frankfurt, Frankfurt, GermanyDepartment of Internal Medicine V, Universitätsklinikum Erlangen, Erlangen, GermanyDepartment of Internal Medicine II, Hematology and Medical Oncology, University Hospital Jena, Jena, GermanyDepartment of Internal Medicine II, Hematology and Medical Oncology, University Hospital Jena, Jena, GermanyDepartment of Internal Medicine V, University of Heidelberg, Heidelberg, GermanyDepartment of Internal Medicine II, University Hospital Würzburg, Würzburg, GermanyDepartment of Internal Medicine V, Nuremberg Hospital North, Paracelsus Medical University, Nuremberg, GermanyDepartment of Hematology, Robert-Bosch-Krankenhaus, Stuttgart, GermanyDepartment of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen and CIO ABCD Aachen, RWTH Aachen, Aachen, GermanyDepartment of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen and CIO ABCD Aachen, RWTH Aachen, Aachen, GermanyDepartment of Medicine A, University Hospital Münster, Münster, GermanyDepartment of Medicine A, University Hospital Münster, Münster, GermanyDepartment of Medicine 3, Klinikum Leverkusen, Leverkusen, GermanyDepartment of Internal Medicine III, Klinikum Chemnitz, Chemnitz, GermanyDepartment of Internal Medicine III, Klinikum Chemnitz, Chemnitz, GermanyDepartment of Hematology, Oncology and Palliative Care, Rems-Murr-Hospital, Winnenden, GermanyDepartment of Internal Medicine, Hematology, Oncology and Immunology, University Hospital Marburg, Marburg, GermanyDepartment of Internal Medicine II, Städtisches Krankenhaus Kiel, Kiel, GermanyDepartment of Hematology, Oncology and Palliative Care, Gemeinschaftsklinikum Mittelrhein, Koblenz, GermanyDepartment of Internal Medicine V, Sozialstiftung Bamberg, Bamberg, GermanyDepartment of Hematology and Oncology, Agaplesion Diakonieklinikum Rotenburg, Rotenburg, GermanyDepartment of Internal Medicine II, DIAKO Bremen, Bremen, GermanyDepartment of Hematology, Oncology and Immunology, St. Bernward Hospital, Hildesheim, GermanyDepartment of Internal Medicine III, Hematology, Oncology and Palliative Care, Helios Dr. Horst Schmidt Klinikum Wiesbaden, Wiesbaden, GermanyDepartment of Hematology and Oncology, Klinikum Bayreuth GmbH, Bayreuth, Germany and Comprehensive Cancer Center-Europäische Metropolregion Nürnberg, Erlangen, GermanyDepartment of Hematology and Oncology, Helios Klinikum Duisburg, Duisburg, GermanyDepartment of Medical Oncology, Hematology and Palliative Care, Marien Hospital Düsseldorf, Düsseldorf, GermanyDepartment of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; Mildred Scheel Early Career Center, Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; National Center for Tumor Diseases Dresden (NCT/UCC), Medical Faculty and University Hospital Dresden, Technical University Dresden, Dresden, Germany; German Cancer Consortium (DKTK), Dresden, GermanyDepartment of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, GermanyDepartment of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, GermanyDepartment of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, GermanyDepartment of Internal Medicine V, University of Heidelberg, Heidelberg, Germany; German Cancer Consortium (DKTK) partner site Dresden, Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, GermanyDepartment of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, GermanyDepartment of Internal Medicine I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, GermanyDepartment of Internal Medicine II, University Hospital Frankfurt, Frankfurt, GermanyDepartment of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; Mildred Scheel Early Career Center, Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; National Center for Tumor Diseases Dresden (NCT/UCC), Medical Faculty and University Hospital Dresden, Technical University Dresden, Dresden, Germany; German Cancer Consortium (DKTK), Dresden, GermanyDepartment of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; Agendix GmbH, Dresden, GermanyDepartment of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, GermanyAbstract: In 2022, the European LeukemiaNet (ELN) risk stratification for patients with acute myeloid leukemia (AML) has been updated. We aimed to validate the prognostic value of the 2022 ELN classification (ELN22) by evaluating 1570 patients with newly diagnosed AML (median age, 56 years) treated with cytarabine-based intensive chemotherapy regimens. Compared with 2017 ELN classification (ELN17), which allocated 595 (38%), 413 (26%), and 562 patients (36%) to the favorable-, intermediate-, and adverse-risk categories, ELN22 classified 575 (37%), 410 (26%), and 585 patients (37%) as favorable, intermediate, and adverse risk, respectively. Risk group allocation was revised in 340 patients (22%). Most patients were reclassified into the ELN22 intermediate- or ELN22 adverse-risk group. The allocation of patients according to the ELN22 risk categories resulted in a significantly distinct event-free survival (EFS), relapse-free survival, and overall survival (OS). Compared with ELN17, reallocation according to the ELN22 recommendations resulted in a significantly improved prognostic discrimination for OS (3-year area under the curve, 0.71 vs 0.67). In patients with ELN22 favorable-risk AML, co-occurring myelodysplasia-related (MR) gene mutations did not significantly affect outcomes. Within the ELN22 adverse-risk group, we observed marked survival differences across mutational groups (5-year OS rate of 21% and 3% in patients with MR gene mutations and TP53 mutations, respectively). In patients harboring MR gene mutations, EZH2-, STAG2-, and ZRSR2-mutated patients showed an intermediate-like OS. In patients with secondary AML and those who underwent allogeneic hematopoietic cell transplantation, EFS and OS significantly differed between ELN22 risk groups, whereas the prognostic abilities of ELN17 and ELN22 classifications were similar. In conclusion, ELN22 improves prognostic discrimination in a large cohort of intensively treated patients with AML. Given the heterogeneous outcome in patients with MR gene alterations, ranging between those of intermediate and adverse risk patients, we suggest re-evaluation of risk allocation in these patients.http://www.sciencedirect.com/science/article/pii/S2473952924006438
spellingShingle Leo Ruhnke
Marius Bill
Sven Zukunft
Jan-Niklas Eckardt
Silvia Schäfer
Sebastian Stasik
Maher Hanoun
Thomas Schroeder
Lars Fransecky
Björn Steffen
Stefan W. Krause
Sebastian Scholl
Andreas Hochhaus
Tim Sauer
Sabrina Kraus
Kerstin Schäfer-Eckart
Martin Kaufmann
Edgar Jost
Tim Brümmendorf
Christoph Schliemann
Jan-Henrik Mikesch
Utz Krug
Mathias Hänel
Anke Morgner
Markus Schaich
Andreas Neubauer
Roland Repp
Dirk Niemann
Ruth Seggewiss-Bernhardt
Achim Meinhardt
Johannes Kullmer
Ulrich Kaiser
Wolfgang Blau
Alexander Kiani
Götz Ulrich Grigoleit
Aristoteles Giagounidis
Alexander A. Wurm
Heidi Altmann
Jan Moritz Middeke
Johannes Schetelig
Carsten Müller-Tidow
Friedrich Stölzel
Claudia D. Baldus
Uwe Platzbecker
Hubert Serve
Martin Bornhäuser
Christian Thiede
Christoph Röllig
Validation of the revised 2022 European LeukemiaNet risk stratification in adult patients with acute myeloid leukemia
Blood Advances
title Validation of the revised 2022 European LeukemiaNet risk stratification in adult patients with acute myeloid leukemia
title_full Validation of the revised 2022 European LeukemiaNet risk stratification in adult patients with acute myeloid leukemia
title_fullStr Validation of the revised 2022 European LeukemiaNet risk stratification in adult patients with acute myeloid leukemia
title_full_unstemmed Validation of the revised 2022 European LeukemiaNet risk stratification in adult patients with acute myeloid leukemia
title_short Validation of the revised 2022 European LeukemiaNet risk stratification in adult patients with acute myeloid leukemia
title_sort validation of the revised 2022 european leukemianet risk stratification in adult patients with acute myeloid leukemia
url http://www.sciencedirect.com/science/article/pii/S2473952924006438
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