Beyond Remission: The Cardiotoxic and Thrombotic Shadow of AML Chemotherapy

Acute myeloid leukemia (AML) remains a devastating hematologic malignancy with persistently high early mortality, particularly among older adults and socioeconomically or geographically disadvantaged populations. Despite therapeutic progress—from cytarabine–anthracycline induction to targeted inhibitors—global disparities persist in diagnosis, treatment access, and supportive care. Among the most underrecognized inequities lies the burden of cardio-thrombotic complications, which disproportionately affect patients with limited access to cardiovascular monitoring or individualized treatment optimization. Anthracyclines induce dose-dependent myocardial injury in up to 20% of patients, while endothelial dysfunction, platelet activation, and inflammatory hypercoagulability amplify the risk of venous and arterial thromboses. These toxicities not only worsen morbidity but also lead to dose reductions, therapy interruptions, and inferior remission outcomes—amplifying survival gaps across populations. Yet, most AML protocols prioritize cytotoxic efficacy over cardio-oncologic safety, perpetuating a structural disparity in comprehensive cancer care. This work integrates mechanistic, clinical, and translational dimensions to construct a unified framework for addressing the cardio-thrombotic burden in AML therapy. We highlight the biological convergence of oxidative stress, mitochondrial dysfunction, endothelial injury, platelet activation, and NET-driven thromboinflammation—factors often magnified in resource-limited settings lacking early biomarker surveillance. We further propose precision-guided innovations, including biomarker-based risk stratification, machine learning–driven prediction models, and functionalized nanomedicine or platelet-hitchhiking drug delivery systems, as equitable solutions to bridge this cardio-onco gap. By conceptualizing cardio-thrombotic injury as both a biological and systemic disparity, our study reframes AML care within an integrative cardio-onco-hematology paradigm aimed at achieving therapeutic equity and improving survival across diverse patient populations.