Randomized Comparison of Cardiotoxicity With 60 Versus 90 mg Daunorubicin in <scp>AML</scp> Induction Therapy

Anthracyclines are an essential component of induction therapy for acute myeloid leukemia (AML), but their optimal dosing and the associated risk for cardiotoxicity remain under debate. The DaunoDouble trial compared daunorubicin at 60 (Dauno60) versus 90 mg/m<sup>2</sup> (Dauno90) in combination with cytarabine (100 mg/m<sup>2</sup> for 7 days) in newly diagnosed AML patients aged 18-65 years. Cardiac function was assessed by left ventricular ejection fraction (LVEF) and cardiac biomarkers (high-sensitivity troponin T [hsTnT], NT-proBNP) before treatment and on Day 15 in 317 randomized patients. Median LVEF declined significantly from 65% [IQR 60%-68.5%] to 61% [IQR 58%-67.8%] across all patients (p < 0.01), without significant differences between treatment arms. NT-proBNP levels measured after induction therapy correlated negatively with LVEF at the same time point (ρ = -0.24, p = 0.02), but did not change significantly during induction-neither between Day 1 and 15 nor between treatment arms. HsTnT levels increased significantly from 5 [IQR 4-8] to 8 ng/L [IQR 6-14] across all patients (p < 0.01), with higher post-induction values in the Dauno90 group (9.5 ng/L [IQR 7-14]) compared to Dauno60 (7 ng/L [IQR 5-14]; p < 0.01). In exploratory subgroup analyses, post-induction hsTnT levels were also significantly higher in patients with obesity and arterial hypertension. These findings provide evidence of a dose-dependent cardiotoxic effect of daunorubicin, already apparent at standard induction doses, and underscore the importance of early cardiac monitoring. Long-term follow-up will be essential to determine the clinical significance of these early changes. Trial Registration: ClinicalTrials.gov identifier: NCT02140242.

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Journal
American Journal of Hematology
Published
2026-01-05
DOI
https://doi.org/10.1002/ajh.70160
Primary Topic
Acute Myeloid Leukemia Research
Type
article
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article

Randomized Comparison of Cardiotoxicity With 60 Versus 90 mg Daunorubicin in AML Induction Therapy

C Schmid, Jan‐Henrik Mikesch, A. Neubauer, C Thiede et al.
American Journal of Hematology
Acute Myeloid Leukemia Research
article

Randomized Comparison of Cardiotoxicity With 60 Versus 90 mg Daunorubicin in AML Induction Therapy

C Schmid, Jan‐Henrik Mikesch, A. Neubauer, C Thiede, Markus Schaich, Sabine Käyser, Sebastian Scholl, Björn Steffen, Martin Bornhäuser, G. Held, Claudia Dorothea Baldus, B Weinbergerová, Andreas Hochhaus, G Ehninger, Katharina Schmidt‐Brücken, Dirk Niemann, Annett Haake, Friedrich Stölzel, W. E. Berdel, Edgar Jost, Regina Herbst, Frank Fiebig, Jolana Mertová, Mathias Hänel, Nael Alakel, Tomáš Szotkowski, Lars R. Fransecky, Christoph Schliemann, Andreas Burchert, Maher Hanoun, Stefan W. Krause, Hubert Serve, Jan Novák, Tim Sauer, C. Carsten Müller‐Tidow, Johannes Schetelig, Uwe Platzbecker, Jan Moritz Middeke, Kerstin Schäfer‐Eckart, Jiri Mayer, Christoph Röllig, Martin Kaufmann, Stefan Markus Dendorfer, Andreas Rank, Michael Kramer
article en

Abstract

Anthracyclines are an essential component of induction therapy for acute myeloid leukemia (AML), but their optimal dosing and the associated risk for cardiotoxicity remain under debate. The DaunoDouble trial compared daunorubicin at 60 (Dauno60) versus 90 mg/m<sup>2</sup> (Dauno90) in combination with cytarabine (100 mg/m<sup>2</sup> for 7 days) in newly diagnosed AML patients aged 18-65 years. Cardiac function was assessed by left ventricular ejection fraction (LVEF) and cardiac biomarkers (high-sensitivity troponin T [hsTnT], NT-proBNP) before treatment and on Day 15 in 317 randomized patients. Median LVEF declined significantly from 65% [IQR 60%-68.5%] to 61% [IQR 58%-67.8%] across all patients (p < 0.01), without significant differences between treatment arms. NT-proBNP levels measured after induction therapy correlated negatively with LVEF at the same time point (ρ = -0.24, p = 0.02), but did not change significantly during induction-neither between Day 1 and 15 nor between treatment arms. HsTnT levels increased significantly from 5 [IQR 4-8] to 8 ng/L [IQR 6-14] across all patients (p < 0.01), with higher post-induction values in the Dauno90 group (9.5 ng/L [IQR 7-14]) compared to Dauno60 (7 ng/L [IQR 5-14]; p < 0.01). In exploratory subgroup analyses, post-induction hsTnT levels were also significantly higher in patients with obesity and arterial hypertension. These findings provide evidence of a dose-dependent cardiotoxic effect of daunorubicin, already apparent at standard induction doses, and underscore the importance of early cardiac monitoring. Long-term follow-up will be essential to determine the clinical significance of these early changes. Trial Registration: ClinicalTrials.gov identifier: NCT02140242.

American Journal of HematologyVol. 101(3)
Goethe University Frankfurt (DE), Public Agenda (US), Philipps University of Marburg (DE), Cognizant (United States) (US), University of Mannheim (DE), Charles University (CZ), Heidelberg University (DE), University Hospital Augsburg (DE), University Hospital Heidelberg (DE), Robert Bosch Hospital (DE), Heidelberg University of Education (DE), Universitätsklinikum Erlangen (DE), Westpfalz Klinikum (DE), Rems-Murr-Klinikum (DE), Institute of Haematology and Blood Transfusion (CZ), Nuremberg Hospital (DE), University Hospital Brno (CZ), University Hospital Münster (DE), National Center for Tumor Diseases (DE), University Hospital Schleswig-Holstein (DE), Essen University Hospital (DE), Universitätsklinikum Aachen (DE), University Hospital Leipzig (DE), University Hospital Frankfurt (DE), Jena University Hospital (DE), Gemeinschaftsklinikum Mittelrhein (DE), University Hospital Kralovske Vinohrady (CZ), University Medical Centre Mannheim (DE), Klinikum Chemnitz (DE), University of Duisburg-Essen (DE), Palacký University Olomouc (CZ), Technische Universität Dresden (DE), Heidelberg University (US), RWTH Aachen University (DE), University of Lübeck (DE)
Technische Universität Dresden
Good health and well-being
Openalex Percentile: Top 95%
Acute Myeloid Leukemia Research
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