Longitudinal evaluation of early and late anthracycline cardiotoxicity in children with AML

被引:68
作者
Creutzig, Ursula
Diekamp, Sylke
Zimmermann, Martin
Reinhardt, Dirk
机构
[1] Univ Munster, Childrens Hosp, Dept Pediat Hematol & Oncol, D-4400 Munster, Germany
[2] Sch Med, Dept Pediat Hematol & Oncol, Hannover, Germany
关键词
AML; children; early anthracycline cardiotoxicity; late anthracycline cardiotoxicity;
D O I
10.1002/pbc.21105
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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). Procedure. 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. Conclusion. In spite of a highly intensive and effective treatment, the frequency of anthracycline-associated cardiomyopathy was low in the AML-BFM studies. Pediatr Blood Cancer 2007;48:651-662. (c) 2006 Wiley-Liss, Inc.
引用
收藏
页码:651 / 662
页数:12
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