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

Area of Science:

• Cardiology
• Hematology
• Oncology

Background:

• Anthracyclines are vital for acute myeloid leukemia (AML) induction therapy.
• Optimal anthracycline dosing and cardiotoxicity risks are debated.
• Daunorubicin is a key anthracycline used in AML treatment.

Purpose of the Study:

• To compare the cardiotoxic effects of two daunorubicin doses (60 vs. 90 mg/m²) in AML induction therapy.
• To assess cardiac function using left ventricular ejection fraction (LVEF) and biomarkers.
• To investigate the dose-dependent cardiotoxicity of daunorubicin.

Main Methods:

• The DaunoDouble trial randomized 317 newly diagnosed AML patients (18-65 years) to daunorubicin 60 or 90 mg/m² with cytarabine.
• Cardiac function was evaluated via LVEF and cardiac biomarkers (hsTnT, NT-proBNP) pre-treatment and on Day 15.
• Statistical analyses compared changes in LVEF and biomarkers between treatment arms and over time.

Main Results:

• LVEF significantly declined across all patients, with no significant difference between daunorubicin dose groups.
• High-sensitivity troponin T (hsTnT) levels increased significantly, with higher levels observed in the 90 mg/m² group compared to the 60 mg/m² group.
• Elevated post-induction hsTnT levels were also noted in patients with obesity and arterial hypertension.

Conclusions:

• Daunorubicin demonstrates a dose-dependent cardiotoxic effect, even at standard induction doses.
• Increased hsTnT levels suggest myocardial injury associated with higher daunorubicin doses.
• Early cardiac monitoring is essential during AML induction therapy to detect potential cardiotoxicity.