Longitudinal evaluation of early and late anthracycline cardiotoxicity in children with AML
Longitudinal evaluation of early and late anthracycline cardiotoxicity in children with AML
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DOI：
10.1002/pbc.21105
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发表时间：
2007-06-15
影响因子：
3.2
通讯作者：
Reinhardt, Dirk
中科院分区：
文献类型：
--
作者：
Creutzig, Ursula;Diekamp, Sylke;Reinhardt, Dirk
背景蒽环类药物是治疗急性髓细胞白血病（AML）的有效药物。然而，它们的使用受到心肌病的限制，在累积剂量为300 mg/m2（相当于柔红霉素）时就已经发生在儿童中。评价儿童AML患者蒽环类药物相关心肌病的发生率，在试验AML-BFM 93/98中，分析了1993年至2003年期间接受治疗的1，207例< 18岁患者的临床和亚临床心脏毒性（强化AML化疗后> 1年）：1，010例方案患者患有新发AML，121例患有唐氏综合征（DS）-AML，76例患有继发性AML。蒽环类药物的累积剂量通常与风险相适应：300-450 mg/m2，使用1-4小时输注蒽环类药物，假定潜在心脏毒性最低。885例患者（73%）符合早期心脏毒性分析的条件，547例患者（45%）符合晚期心脏毒性分析的条件（1，399例随访数据）。38例（4.3%）患者，包括3例DS-AML和1例继发性AML，患有早期心肌病。5年后，4名患者显示出暂时或持续的缩短分数降低，导致1名DS-AML患者死亡。包括这4例患者在内，16例患者出现晚期心肌病（11年后的累积发病率：5% +/- 1%）。9例患者（2.5 +/- 1%）表现出临床症状，其中5例持续异常缩短分数。7例患者暂时发生晚期亚临床心肌病。晚期临床心肌病主要发生在第二次蒽环类药物治疗的患者（继发性恶性肿瘤）和早期心脏毒性患者。尽管进行了高强度和有效的治疗，但在AML-BFM研究中蒽环类药物相关心肌病的发生率较低。儿科血液癌症2007;48：651-662。(c)2006威利-利斯公司
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.