Late cardiac effects of anthracycline containing therapy for childhood acute lymphoblastic leukemia.
BACKGROUND
At present about 80% of children with acute lymphoblastic leukemia (ALL) will be cured following treatment with multi-drug chemotherapy. A major concern for this growing number of survivors is the risk of late effects of treatment. The aim of this study was to determine whether signs of cardiomyopathy were present in patients treated in childhood with cumulative anthracycline doses of less than 300 mg/m(2).


METHODS
Evaluation of cardiac function in a cohort of 63 long-term survivors in first continuous remission following treatment of ALL with multi-drug chemotherapy including anthracyclines was performed using standard M-mode echocardiography and tissue doppler imaging (TDI). Associations between age at diagnosis, cumulative dose of anthracycline, sex, length of follow-up, and deviations from normal values in M-mode echocardiograms were evaluated using univariate and multivariate regression analysis. TDI data were compared to normal values using Wilcoxon matched-pairs signed-ranks test.


RESULTS
By standard M-mode echocardiography the most significant findings were diastolic dilation of the left ventricle, thinner interventricular septum (IVS), decreased left ventricular mass (LVM) in females, follow-up dependent dilation of the left ventricle in systole and follow-up dependent decrease in ejection fraction (EF). TDI abnormalities included signs of early diastolic dysfunction and myocardial hypertrophy, and were also found in structures that appeared normal by M-mode echocardiography.


CONCLUSIONS
This study adds to the growing evidence that even low to moderate doses of anthracyclines might lead to progressive cardiac dysfunction. It is important that children treated with anthracyclines receive life long follow-up for signs of cardiomyopathy.
Rathe
Mathias
M
Department of paediatrics, Odense University Hospital, Odense, Denmark.
Carlsen
Niels L T
NL
Oxhøj
Henrik
H
D000293:Adolescent; D000367:Age Factors; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography / Q000379:methods; D015150:Echocardiography, Doppler / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy*; D012044:Regression Analysis; D012307:Risk Factors; D012737:Sex Factors; D013995:Time; D016896:Treatment Outcome
D018943:Anthracyclines