Overview
A comprehensive meta-analysis led by researchers from the Netherlands sheds new light on the risk of heart failure in patients with acute myeloid leukemia (AML) who receive anthracycline-based induction therapy. By systematically reviewing 41 studies including 5,995 AML patients, the study consolidates what clinicians have long suspected: anthracyclines, while effective for achieving remission, carry a dose- and drug-dependent risk of cardiotoxicity that warrants vigilant monitoring throughout and after treatment.
Key Findings
The pooled proportion of heart failure among AML patients treated with anthracyclines was 3.2%. This risk is not evenly distributed across drugs: 2.3% with daunorubicin, 5.0% with idarubicin, and notably higher at 10.2% with mitoxantrone. In addition to heart failure, secondary cardiovascular adverse events were common but frequently underreported in the available studies, underscoring gaps in how toxicity is captured and communicated in oncology trials.
Why Cardiotoxicity Remains a Major Concern
Anthracyclines have a well-established role in AML remission induction, but their cardiotoxic effects are dose-dependent and can be exacerbated by existing cardiovascular risk factors. A key challenge is the reliance of many grading systems on symptomatic manifestations, which means subclinical declines in cardiac function are often missed. Early dysfunction may not produce noticeable symptoms until substantial damage has occurred, potentially limiting reversibility.
Gaps in Monitoring and Reporting
The analysis identified frequent shortcomings in cardiac monitoring during therapy. Routine echocardiography, cardiac biomarkers, and standardized reporting of cardiovascular events were inconsistent across studies. Without consistent data capture, clinicians and researchers face obstacles in understanding the true burden of cardiotoxicity and in making informed cross-drug comparisons. This lack of early signals can delay interventions that might prevent progression to overt heart failure.
Implications for Clinical Practice in AML
For patients with AML undergoing anthracycline therapy, proactive cardiac surveillance should be a standard component of care, regardless of the presence or absence of cardiac symptoms. Standardized reporting of cardiovascular adverse events is essential to generate reliable data that can guide practice and policy. The goal is early detection and timely intervention to halt or reverse cardiac injury before it advances to advanced heart failure.
Recommendations for Improved Care
Based on the current evidence, clinicians should consider implementing comprehensive surveillance protocols during AML treatment that include routine echocardiography, measurement of cardiac biomarkers, and regular assessment of heart function. Multidisciplinary collaboration between oncologists and cardio-oncologists is crucial for tailoring treatment, weighing leukemia control against cardiotoxic risk, and initiating cardioprotective strategies when indicated. Standardized adverse event grading and reporting systems are needed to enhance data quality and comparability across studies and clinical settings.
Future Directions
Future research should prioritize: (1) harmonized definitions and grading for subclinical cardiotoxicity, (2) prospective monitoring protocols integrated into AML trials, and (3) comparative studies evaluating strategies to mitigate risk across different anthracycline regimens. The overarching objective is to preserve long-term cardiac health without compromising leukemia outcomes, thereby improving overall survival and quality of life for AML survivors.
Conclusion
The new systematic review and meta-analysis confirm a measurable risk of heart failure in AML patients treated with anthracyclines and reveal substantial variability by drug. They also highlight important gaps in monitoring and reporting. By embracing routine cardiac surveillance, standardized adverse event reporting, and proactive cardioprotective approaches, clinicians can better manage cardiotoxicity, reduce progression to heart failure, and enhance long-term outcomes for AML patients.
Reference
Geels J et al. Heart failure in patients with acute myeloid leukemia (AML) treated with anthracycline agents during remission induction therapy: a systematic review and meta-analysis. Leukaemia. 2025; https://doi.org/10.1038/s41375-025-02753-w.
