Anthracycline-associated cardiotoxicity casts long shadow
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1. Creutzig U, et al. Longitudinal evaluation of early and late anthracycline cardiotoxicity in children with AML. Pediatric Blood and Cancer 48: 651-662, No. 7, 15 Jun 2007. 2. Rathe M, et al. Late cardiac effects of anthracycline containing therapy for childhood acute lymphoblastic leukemia. Pediatric Blood and Cancer 48: 663-667, No. 7, 15 Jun 2007. 801052219
Relatively low risk The incidence of both early and late clinical and subclinical cardiomyopathy is relatively low among paediatric patients with acute myelogenous leukaemia (AML) treated under the AML-BFM 93 and 98 trial protocols, report researchers from Germany.1 The researchers evaluated anthracycline-associated cardiomyopathy in 1207 paediatric AML patients who received a cumulative anthracycline dose of 300–450 mg/m2; 73% and 45% of patients were eligible for analysis of early and late cardiotoxicity, respectively. Based on ECG and echocardiography data, 24 patients developed acute subclinical cardiomyopathy during or within 1 year of intensive AML chemotherapy and 14 developed clinical cardiomyopathy. Among the latter group, there was one death related to cardiomyopathy and one patient in the subclinical group experienced persistent cardiotoxicity. Long-term follow-up showed that 16 patients presented with late subclinical or clinical cardiomyopathy within a median of 5 years; of these, four had already presented with early abnormal cardiac findings. There was one death among the nine patients with clinical cardiomyopathy and persistent cardiotoxicity in four patients. The researchers did note that the incidence of late cardiomyopathy for patients with secondary AML was "extremely high" at 60%, suggesting that this cohort was more sensitive to additional anthracycline therapy than relapsed AML patients treated under other trial protocols.
Risk even at low doses Adding to the picture, researchers from Denmark report that "even low doses of anthracycline may lead to cardiac dysfunction with time".2 They evaluated cardiac function in 63 long-term survivors who were in their first continuous remission following anthracycline-based chemotherapy for acute lymphoblastic leukaemia (ALL). The patients, aged < 15 years at diagnosis, had received cumulative doses of anthracyclines of < 300 mg/m2. For the survivor cohort as a whole, standard M-mode echocardiography detected significantly thinner interventricular septums and increased left ventricular (LV) dimension during diastole. In addition, reduced LV mass in females and a low ejection fraction (EF; < 60%) in nine patients were detected; of the latter, seven had received cumulative doses > 200 mg/m2. Tissue Doppler imaging (TDI) detected signs of early diastolic dysfunction and myocardial hypertrophy, as well as abnormalities in structures that appeared normal on M-mode echocardiography. According to the researchers, their data suggest that "cardiac function may worsen with time" as multivariate regression analysis showed a significant association between length of follow-up and LV systolic dilatation and
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