Long-term cardiac follow-up of children treated with anthracycline doses of 300 mg/m2 or less for acute lymphoblastic leukemia.
BACKGROUND
The cardiotoxic effect of anthracyclines has been well described for moderate to high cumulative doses (>350 mg/m(2)). However, the question of whether sub-clinical signs of cardiomyopathy may develop and progress over time in children receiving doses of <350 mg/m(2) is controversial. The aim of the present study was to examine cardiac function with serial echocardiography from diagnosis to last follow-up, relapse, or death, and to investigate whether suspected risk factors (e.g., age at diagnosis, gender, cumulative dose, and length of follow-up) had a significant influence on cardiac function.


METHODS
An unselected cohort of 80 patients treated with multi-drug chemotherapy including anthracycline doses of 300 mg/m(2) or less for childhood acute lymphoblastic leukemia was followed with serial echocardiograms. The deviations of each echocardiogram from normal values for the same age and body-surface areas were calculated. The influences of risk factors were analyzed using univariate and multivariate regression. Lowess curves of time dependence were calculated.


RESULTS
All echocardiographic parameters including ejection fraction (EF) deteriorated significantly over time. Male gender was significantly associated with systolic dilatation of the left ventricle and positively associated with left ventricular mass. Reduction of EF was significantly associated with age at diagnosis and male gender.


CONCLUSIONS
Anthracycline doses of <300 mg/m(2) may contribute to a decline in cardiac function over time. Although the deterioration in cardiac parameters was not associated with clinical symptoms, life-long cardiac surveillance for these patients is important to establish the impact of low-dose anthracycline therapy on long-term cardiac health.
Rathe
Mathias
M
H.C. Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
Carlsen
Niels Lauritz Torp
NL
Oxhøj
Henrik
H
Nielsen
Gunner
G
D000293:Adolescent; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000000981:diagnostic imaging; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012737:Sex Factors; D013318:Stroke Volume / Q000187:drug effects
D018943:Anthracyclines