Anthracycline-related cardiotoxicity in older patients with acute myeloid leukemia: a Young SIOG review paper

Abstract

The incidence of acute myeloid leukemia (AML) increases with age. Intensive induction chemotherapy containing cytarabine and an anthracycline has been part of the upfront and salvage treatment of AML for decades. Anthracyclines are associated with a significant risk of cardiotoxicity (especially anthracycline-related left ventricular dysfunction [ARLVD]). In the older adult population, the higher prevalence of cardiac comorbidities and risk factors may further increase the risk of ARLVD. In this article of the Young International Society of Geriatric Oncology group, we review the prevalence of ARLVD in patients with AML and factors predisposing to ARLVD, focusing on older adults when possible. In addition, we review the assessment of cardiac function and management of ARLVD during and after treatment. It is worth noting that only a minority of clinical trials focus on alternative treatment strategies in patients with mildly declined left ventricular ejection fraction or at a high risk for ARLVD. The limited evidence for preventive strategies to ameliorate ARLVD and alternative strategies to anthracycline use in the setting of cardiac comorbidities are discussed. Based on extrapolation of findings from younger adults and nonrandomized trials, we recommend a comprehensive baseline evaluation of cardiac function by imaging, cardiac risk factors, and symptoms to risk stratify for ARLVD. Anthracyclines remain an appropriate choice for induction although careful risk-stratification based on cardiac disease, risk factors, and predicted chemotherapy-response are warranted. In case of declined left ventricular ejection fraction, alternative strategies should be considered.

Understanding the common mechanisms of heart and skeletal muscle wasting in cancer cachexia

“…Interestingly, comparing acute leukemia (AL) patients with other cancer patients, it has been reported that AL is linked to myocardial dysfunction 115 . Moreover, the rate of AL patients who develop heart failure significantly increases upon chemotherapy 116 , 117 . Consequently, although leukemia patients do not commonly develop cachexia 118 , the associated cardiac dysfunction may result in an increased susceptibility of AL patients to the development of the wasting syndrome.…”

AML: Auf der Suche nach Risikofaktoren für die Anthrazyklin-induzierte Kardiomyopathie

“…Die akute myeloische Leukämie (AML) ist insbesondere eine Erkrankung des älteren Patienten, daher sind kardiale Komorbiditäten häufig Therapie-limitierend oder erschwerend. Erschwerend scheint eine Anthrazyklin-induzierte Kardiomyopathie (AiK) bei dieser Entität häufiger zu sein [1]. Eine mögliche kausale Verbindung ist die klonale Hämatopoese von unbestimmtem Potential (CHIP), welche zur Entstehung von Leukämien [2, 3] als auch kardiovaskulären Ereignissen [4, 5] prädisponiert.…”

Epigenetic Changes Associated With Anthracycline‐Induced Cardiotoxicity

“…14 Comorbid conditions, such as cardiac diseases, arterial hypertension, diabetes, dyslipidemia, and renal failure, are also significant risk factors. 15,16 Patients treated with anthracyclines are five times more likely to have reduced left ventricular ejection fraction or develop HF compared with those treated with other non-anthracycline chemotherapy. 4 AIC can be acute or chronic, with acute cardiotoxicity occurring during the treatment or immediately afterward; this entails pericarditis-myocarditis and arrhythmias, which are both possibly reversible.…”

“…Other factors, such as female sex, age above 60 years, pediatric population, and previous radiotherapy have also been associated with a higher risk of cardiotoxicity 14 . Comorbid conditions, such as cardiac diseases, arterial hypertension, diabetes, dyslipidemia, and renal failure, are also significant risk factors 15,16 …”