Background Chronic myeloid leukemia (CML) is a hematological malignancy driven by the BCR-ABL fusion gene, which has become the target of tyrosine kinase inhibitors (TKIs). These therapies have transformed CML outcomes, significantly improving survival rates. However, TKIs are associated with cardiovascular toxicities that represent a critical challenge in the long-term management of patients. Purpose This study aimed to evaluate the prevalence, progression, and clinical impact of cardiovascular toxicities in CML patients undergoing treatment with BCR-ABL TKIs, and to identify early markers for improved surveillance and management strategies. Methods A retrospective analysis was conducted on 60 CML patients treated with TKIs at the Echocardiography and Cardiomyopathies Lab. Baseline and follow-up cardiovascular assessments included advanced echocardiographic techniques such as global longitudinal strain (GLS) and mechanical dispersion (MD). Patients were stratified according to ESC cardio-oncology guidelines into low, moderate, high, and very high cardiovascular risk categories. Statistical analyses assessed associations between TKI use, risk scores, and cardiovascular outcomes. Results At baseline, 65% of patients had hypertension, and Dasatinib was the most frequently used TKI (41.6%). While most patients had preserved left ventricular function, borderline elevations in E/e’ ratios and isolated cases of pericardial (3.3%) and pleural (5%) effusions were noted. Over a median follow-up of 18 months, the high and very high-risk groups showed significant worsening of GLS and MD, alongside higher rates of arrhythmias and arterial occlusions. A higher incidence of adverse cardiovascular events was observed in patients who treated with second- and third-generation TKIs, particularly Nilotinib and Ponatinib. Conclusions TKI-induced cardiovascular toxicities are clinically significant in CML patients, particularly among those with pre-existing cardiovascular risks or treated with second- and third-generation inhibitors. Routine use of advanced echocardiographic techniques, combined with strict adherence to cardio-oncology surveillance protocols, is essential for early detection and management of subclinical cardiotoxicity. A multidisciplinary approach involving oncologists and cardiologists is critical to optimizing patient outcomes while minimizing treatment-related morbidity.

Cardiovascular toxicity in CML patients treated with BCR-ABL inhibitors: relevance of early detection and management of cardiovascular follow-up

Faro, D C;Impellizzeri, S G;Monte, I P
2025-01-01

Abstract

Background Chronic myeloid leukemia (CML) is a hematological malignancy driven by the BCR-ABL fusion gene, which has become the target of tyrosine kinase inhibitors (TKIs). These therapies have transformed CML outcomes, significantly improving survival rates. However, TKIs are associated with cardiovascular toxicities that represent a critical challenge in the long-term management of patients. Purpose This study aimed to evaluate the prevalence, progression, and clinical impact of cardiovascular toxicities in CML patients undergoing treatment with BCR-ABL TKIs, and to identify early markers for improved surveillance and management strategies. Methods A retrospective analysis was conducted on 60 CML patients treated with TKIs at the Echocardiography and Cardiomyopathies Lab. Baseline and follow-up cardiovascular assessments included advanced echocardiographic techniques such as global longitudinal strain (GLS) and mechanical dispersion (MD). Patients were stratified according to ESC cardio-oncology guidelines into low, moderate, high, and very high cardiovascular risk categories. Statistical analyses assessed associations between TKI use, risk scores, and cardiovascular outcomes. Results At baseline, 65% of patients had hypertension, and Dasatinib was the most frequently used TKI (41.6%). While most patients had preserved left ventricular function, borderline elevations in E/e’ ratios and isolated cases of pericardial (3.3%) and pleural (5%) effusions were noted. Over a median follow-up of 18 months, the high and very high-risk groups showed significant worsening of GLS and MD, alongside higher rates of arrhythmias and arterial occlusions. A higher incidence of adverse cardiovascular events was observed in patients who treated with second- and third-generation TKIs, particularly Nilotinib and Ponatinib. Conclusions TKI-induced cardiovascular toxicities are clinically significant in CML patients, particularly among those with pre-existing cardiovascular risks or treated with second- and third-generation inhibitors. Routine use of advanced echocardiographic techniques, combined with strict adherence to cardio-oncology surveillance protocols, is essential for early detection and management of subclinical cardiotoxicity. A multidisciplinary approach involving oncologists and cardiologists is critical to optimizing patient outcomes while minimizing treatment-related morbidity.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/689501
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