Longitudinal evaluation of early and late anthracycline cardiotoxicity in children with AML.
BACKGROUND
Anthracyclines are effective antineoplastic drugs in acute myelogenous leukemia (AML). However, their use is limited by cardiomyopathy, which occurs in children already at cumulative doses of 300 mg/m(2) (given as daunorubicin equivalent).


METHODS
To evaluate anthracycline-associated cardiomyopathy in pediatric AML-patients, the incidence of early and late (>1 year after intensive AML chemotherapy) clinical and subclinical cardiotoxicity was analyzed out of a total of 1,207 patients <18 years treated between 1993 and 2003 in trials AML-BFM93/98: 1,010 protocol patients with de novo AML, 121 with Down syndrome (DS)-AML, and 76 with secondary AML. The cumulative dose of anthracyclines was generally risk-adapted: 300-450 mg/m(2) using 1-4-hr infusions of anthracyclines with the assumed lowest cardiotoxic potential. Eight hundred eighty-five patients (73%) were eligible for the analysis of early and 547 (45%) of late cardiotoxicity (1,399 follow-up data).


RESULTS
Thirty-eight patients (4.3%), including 3 DS-AML and 1 secondary AML, suffered from early cardiomyopathy. After 5 years, four patients showed temporarily or persistently a reduced shortening fraction, which led to death in one DS-AML patient. Including these 4 patients, late cardiomyopathy was seen in 16 patients (cumulative incidence after 11 years: 5% +/- 1%). Nine patients (2.5 +/- 1%) showed clinical symptoms, five of them had persistent abnormal shortening fraction. Late subclinical cardiomyopathy occurred temporarily in seven patients. Late clinical cardiomyopathy mainly affected patients with a second anthracycline therapy (secondary malignancy) and those with early cardiotoxicity.


CONCLUSIONS
In spite of a highly intensive and effective treatment, the frequency of anthracycline-associated cardiomyopathy was low in the AML-BFM studies.
Creutzig
Ursula
U
Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany. ursula@creutzig.de
Diekamp
Sylke
S
Zimmermann
Martin
M
Reinhardt
Dirk
D
D000208:Acute Disease; D000293:Adolescent; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D004452:Echocardiography / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy*; D008137:Longitudinal Studies; D008297:Male; D010865:Pilot Projects; D012307:Risk Factors; D017741:Survivors; D013995:Time; D016896:Treatment Outcome
D018943:Anthracyclines