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

Dendorfer SM, Schmidt-Brücken K, Kramer M, Steffen B, Schliemann C, Mikesch JH, Alakel N, Herbst R, Hänel M, Hanoun M, Kaufmann M, Weinbergerova B, Schäfer-Eckart K, Sauer T, Neubauer A, Burchert A, Baldus CD, Mertová J, Jost E, Niemann D, Novák J, Krause S, Scholl S, Hochhaus A, Held G, Szotkowski T, Rank A, Schmid C, Fransecky L, Kayser S, Schaich M, Fiebig F, Haake A, Schetelig J, Middeke JM, Stölzel F, Platzbecker U, Thiede C, Müller-Tidow C, Berdel WE, Ehninger G, Mayer J, Serve H, Bornhäuser M, Röllig C (2026)

Publication Type: Journal article

Publication year: 2026

Journal

DOI: 10.1002/ajh.70160

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/m² (Dauno90) in combination with cytarabine (100 mg/m² 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.

Authors with CRIS profile

Involved external institutions

Ruprecht-Karls-Universität Heidelberg Germany (DE) Universitätsklinikum Essen Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsklinikum Münster Germany (DE) Klinikum Chemnitz Germany (DE) Paracelsus Medizinische Privatuniversität, Nürnberg Germany (DE) Universitätsklinikum Augsburg Germany (DE) Gemeinschaftsklinikum Mittelrhein Germany (DE) Universitätsklinikum Aachen (UKA) Germany (DE) Westpfalz-Klinikum Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Rems-Murr-Kliniken Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) University Hospital Brno Czech Republic (CZ) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Fakultní nemocnice Královské Vinohrady Czech Republic (CZ) Universitätsklinikum Jena Germany (DE) Palacky University Olomouc / Univerzita Palackého v Olomouci Czech Republic (CZ) Universitätsklinikum Leipzig Germany (DE)

How to cite

APA:

Dendorfer, S.M., Schmidt-Brücken, K., Kramer, M., Steffen, B., Schliemann, C., Mikesch, J.H.,... Röllig, C. (2026). Randomized Comparison of Cardiotoxicity With 60 Versus 90 mg Daunorubicin in AML Induction Therapy. American Journal of Hematology. https://doi.org/10.1002/ajh.70160

MLA:

Dendorfer, Stefan Markus, et al. "Randomized Comparison of Cardiotoxicity With 60 Versus 90 mg Daunorubicin in AML Induction Therapy." American Journal of Hematology (2026).

BibTeX: Download