Blood Advances (Mar 2025)
Validation of the revised 2022 European LeukemiaNet risk stratification in adult patients with acute myeloid leukemia
- 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
Affiliations
- Leo Ruhnke
- Department 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;
- Marius Bill
- 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, Germany
- Sven Zukunft
- Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany
- Jan-Niklas Eckardt
- 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; Else Kröner Fresenius Center for Digital Health, Technical University Dresden, Dresden, Germany
- Silvia Schäfer
- 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
- Sebastian Stasik
- Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany
- Maher Hanoun
- Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Thomas Schroeder
- Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
- Lars Fransecky
- Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
- Björn Steffen
- Department of Internal Medicine II, University Hospital Frankfurt, Frankfurt, Germany
- Stefan W. Krause
- Department of Internal Medicine V, Universitätsklinikum Erlangen, Erlangen, Germany
- Sebastian Scholl
- Department of Internal Medicine II, Hematology and Medical Oncology, University Hospital Jena, Jena, Germany
- Andreas Hochhaus
- Department of Internal Medicine II, Hematology and Medical Oncology, University Hospital Jena, Jena, Germany
- Tim Sauer
- Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
- Sabrina Kraus
- Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany
- Kerstin Schäfer-Eckart
- Department of Internal Medicine V, Nuremberg Hospital North, Paracelsus Medical University, Nuremberg, Germany
- Martin Kaufmann
- Department of Hematology, Robert-Bosch-Krankenhaus, Stuttgart, Germany
- Edgar Jost
- Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen and CIO ABCD Aachen, RWTH Aachen, Aachen, Germany
- Tim Brümmendorf
- Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital Aachen and CIO ABCD Aachen, RWTH Aachen, Aachen, Germany
- Christoph Schliemann
- Department of Medicine A, University Hospital Münster, Münster, Germany
- Jan-Henrik Mikesch
- Department of Medicine A, University Hospital Münster, Münster, Germany
- Utz Krug
- Department of Medicine 3, Klinikum Leverkusen, Leverkusen, Germany
- Mathias Hänel
- Department of Internal Medicine III, Klinikum Chemnitz, Chemnitz, Germany
- Anke Morgner
- Department of Internal Medicine III, Klinikum Chemnitz, Chemnitz, Germany
- Markus Schaich
- Department of Hematology, Oncology and Palliative Care, Rems-Murr-Hospital, Winnenden, Germany
- Andreas Neubauer
- Department of Internal Medicine, Hematology, Oncology and Immunology, University Hospital Marburg, Marburg, Germany
- Roland Repp
- Department of Internal Medicine II, Städtisches Krankenhaus Kiel, Kiel, Germany
- Dirk Niemann
- Department of Hematology, Oncology and Palliative Care, Gemeinschaftsklinikum Mittelrhein, Koblenz, Germany
- Ruth Seggewiss-Bernhardt
- Department of Internal Medicine V, Sozialstiftung Bamberg, Bamberg, Germany
- Achim Meinhardt
- Department of Hematology and Oncology, Agaplesion Diakonieklinikum Rotenburg, Rotenburg, Germany
- Johannes Kullmer
- Department of Internal Medicine II, DIAKO Bremen, Bremen, Germany
- Ulrich Kaiser
- Department of Hematology, Oncology and Immunology, St. Bernward Hospital, Hildesheim, Germany
- Wolfgang Blau
- Department of Internal Medicine III, Hematology, Oncology and Palliative Care, Helios Dr. Horst Schmidt Klinikum Wiesbaden, Wiesbaden, Germany
- Alexander Kiani
- Department of Hematology and Oncology, Klinikum Bayreuth GmbH, Bayreuth, Germany and Comprehensive Cancer Center-Europäische Metropolregion Nürnberg, Erlangen, Germany
- Götz Ulrich Grigoleit
- Department of Hematology and Oncology, Helios Klinikum Duisburg, Duisburg, Germany
- Aristoteles Giagounidis
- Department of Medical Oncology, Hematology and Palliative Care, Marien Hospital Düsseldorf, Düsseldorf, Germany
- Alexander A. Wurm
- 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, Germany
- Heidi Altmann
- Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany
- Jan Moritz Middeke
- Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany
- Johannes Schetelig
- Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany
- Carsten Müller-Tidow
- Department 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, Germany
- Friedrich Stölzel
- Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
- Claudia D. Baldus
- Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
- Uwe Platzbecker
- Department of Internal Medicine I, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany
- Hubert Serve
- Department of Internal Medicine II, University Hospital Frankfurt, Frankfurt, Germany
- Martin Bornhäuser
- 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, Germany
- Christian Thiede
- Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany; Agendix GmbH, Dresden, Germany
- Christoph Röllig
- Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany
- Journal volume & issue
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Vol. 9,
no. 6
pp. 1392 – 1404
Abstract
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.
