Since 2017, targeted therapies combined with conventional intensive chemotherapy have started to improve outcomes of patients with acute myeloid leukemia (AML). However, even before these innovations, outcomes with intensive chemotherapy had improved, which has not yet been extensively studied. Thus, we used a large pan-European multicenter dataset of the HARMONY Alliance to evaluate treatment-time dependent outcomes over two decades. In 5,359 AML patients, we compared the impact of intensive induction therapy on outcome over four consecutive 5-year calendar periods from 1997 to 2016. During that time, the 5-year survival of AML patients improved significantly, also across different genetic risk groups. In particular, the 60-day mortality rate dropped from 13.0% to 4.7% over time. The independent effect of calendar periods on outcome was confirmed in multivariate models. Improvements were documented both for patients <60 and ≥60 years old, and in those treated with and without consolidating allogeneic hematopoietic stem cell transplantation (alloHCT). While survival of AML elderly patients remains poor, patients ≥60 years old overall have a 20% survival benefit at 5 years if they receive an alloHCT. While further outcome improvement in intensively treated AML patients will likely be driven by targeted treatment approaches, this pan-European HARMONY dataset can serve as a multicenter comparator for future studies.

AbbVie Deutschland GmbH and Co KG Wiesbaden

Bayer AG Pharmaceuticals Division Berlin

Center Amsterdam UMC location VUMC Netherlands

Department for Hematology Cell Therapy and Hemostaseology University of Leipzig Medical Center Leipzig

Department of Haematology and Wellcome MRC Cambridge Stem Cell Institute University of Cambridge Cambridge

Department of Hematology Amsterdam University Medical Center location Vrije Universiteit Amsterdam Amsterdam Netherlands

Department of Hematology and Oncology Marienhospital University Hospital Ruhr University Bochum Bochum

Department of Hematology Blood Neoplasm and Bone Marrow Transplantation Wroclaw Medical University

Department of Hematology Oncology and Cancer Immunology Campus Virchow Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin Berlin

Department of Hematology Oncology and Cancer Immunology Campus Virchow Charité Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin Berlin Germany; German Cancer Consortium Heidelberg

Department of Internal Medicine 1 University Hospital Dresden Dresden

Department of Internal Medicine 3 University Hospital Ulm Ulm

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Masaryk University

Department of Medical and Surgical Sciences DIMEC University of Bologna Bologna

Department of Pediatrics 3 University Hospital Essen University Duisburg Essen Essen

Division of Biostatistics German Cancer Research Center Heidelberg

GMV Innovating Solutions Valencia

Hematology Department Hospital Universitario 12 de Octubre Complutense University CNIO Madrid

Hematology Department University Hospital of Salamanca Salamanca

Hospital Santa Creu Sant Pau Barcelona

Institute of Biomedical Research of Salamanca Salamanca

Institute of Biomedical Research of Salamanca Salamanca Spain; Hematology Department University Hospital of Salamanca Salamanca

IRCCS Humanitas Research Hospital via Manzoni 56 20089 Rozzano Milan Italy; and Department of Biomedical Sciences Humanitas University Via Rita Levi Montalcini 4 20072 Pieve Emanuele Milan

IRCCS Istituto delle Scienze Neurologiche di Bologna Bologna Italia

MLL Munich Leukemia Laboratory Munich

Patrick G Johnston Centre for Cancer Research Queen's University Belfast Belfast

Uppsala University Hospital Uppsala

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