Long Term Data on Anthracycline Cardiotoxicity in 547 Children with AML.

Anthracyclines are effective antineoplastic drugs in acute mylogenous leukemia (AML) and dose intensity and cumulative doses are especially important. However, the use of anthracyclines is limited by cardiotoxicity, which occurs already at 300 mg/m² cumulative doses (given as daunorubicin dosage) in children. To evaluate anthracycline-associated cardiomyopathy in pediatric AML-patients, the incidence of late clinical and subclinical cardiotoxicity (using echocardiography) was analysed in studies AML-BFM 93 and 98. Out of a total of 1,207 patients under 18 years, 547 (45%) patients were eligible for the analysis of late cardiotoxicity - de novo AML: 470 of 1,010 (46%), AML-Down syndrome: 69 of 121 (57%), secondary AML 8 of 76 (11%) -, median follow-up 5.3 years (0.8–11.7 years) after diagnosis. The cumulative dose of anthracyclines was risk-adapted between 300 and 450 mg/m² or even higher in patients with secondary AML.

Results: Late cardiomyopathy was seen in 16 patients, cumulative incidence (CI) after 11 years 5±1% (de novo patients: 4±1%), including 4 of 38 patients (10.5%) who suffered already from early cardiomyopathy. Nine of these 16 patients (CI 2.5±1%) showed clinical symptoms, with persistent abnormal shortening fraction in 5 of them, which led to death in one AML-Down syndrome patient. Late subclinical cardiomyopathy occurred temporarily in 7 patients. Late clinical cardiomyopathy mainly effected patients with a second anthracycline therapy (3 of 8 with AML as secondary malignancy) and those with early cardiotoxicity. Using anthracyclines risk-adapted or administering long-term infusion might have contributed to the low rate of cardiomyopathy in AML de novo patients.