title: Longitudinal evaluation of early and late anthracycline cardiotoxicity in children with AML.
abstract: 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.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany. ursula@creutzig.de
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.forename: Sylke
authors.initials: S
authors.lastname: Diekamp
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
mesh_terms: 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
chemical_list: D018943:Anthracyclines