Nysom K, Holm K, Lipsitz S R, Mone S M, Colan S D, Orav E J, Sallan S E, Olsen J H, Hertz H, Jacobsen J R, Lipshultz S E
Department of Pediatrics, National University Hospital Rigshospitalet, Copenhagen, Denmark.
J Clin Oncol. 1998 Feb;16(2):545-50. doi: 10.1200/JCO.1998.16.2.545.
Late anthrocycline cardiotoxicity after treatment for childhood cancer is common and often progressive. A safe anthracycline dose that will not result in late cardiac abnormalities has not been established due to the limited dose ranges used in existing studies.
To determine the relationship between cumulative anthracycline dose and late cardiotoxicity, we performed echocardiograms on 189 survivors of childhood acute lymphoblastic leukemia a median of 8.1 years (range, 2.0 to 23.4) after completion of anthracycline therapy. Patients were treated according to protocols that used widely varying cumulative anthracycline doses, but comparable nonanthracycline chemotherapy. Patients were divided into four groups based on the city of treatment and cumulative anthracycline dose: Copenhagen, 0 to 23 mg/m2 (n = 32); Boston, 45 mg/m2 (n = 17); Copenhagen, 73 to 301 mg/m2 (n = 53); and Boston, 244 to 550 mg/m2 (n = 87). Left ventricular dimension and fractional shortening were adjusted for sex and age or body-surface area through use of a control population (n = 296), and then compared among the four groups.
Mean left ventricular dimension was significantly increased in the high-dose Boston group (observed:predicted value, 4.57 cm:4.45 cm; P = .002) and significantly higher than in the two Copenhagen groups. In the three lower-dose groups, there was no significant increase in mean left ventricular dimension, and the groups were not significantly different from each other. Similarly, the mean left ventricular fractional shortening was significantly depressed in the high-dose Boston group (observed:predicted value, 29.0%:33.8%; P = .0001) and significantly lower than in the three lower-dose groups.
Depressed left ventricular fractional shortening and left ventricular dilatation were uncommon years after treatment of childhood leukemia when cumulative anthracycline doses were < or = 300 mg/m2.
儿童癌症治疗后迟发性蒽环类药物心脏毒性很常见且往往呈进行性发展。由于现有研究中使用的剂量范围有限，尚未确定不会导致晚期心脏异常的安全蒽环类药物剂量。
为确定累积蒽环类药物剂量与迟发性心脏毒性之间的关系，我们对189例儿童急性淋巴细胞白血病幸存者在完成蒽环类药物治疗后中位时间8.1年（范围2.0至23.4年）进行了超声心动图检查。患者按照使用广泛不同累积蒽环类药物剂量但可比的非蒽环类化疗方案进行治疗。根据治疗城市和累积蒽环类药物剂量将患者分为四组：哥本哈根，0至23mg/m²（n = 32）；波士顿，45mg/m²（n = 17）；哥本哈根，73至301mg/m²（n = 53）；以及波士顿，244至550mg/m²（n = 87）。通过使用对照人群（n = 296）对左心室尺寸和缩短分数进行性别和年龄或体表面积校正，然后在四组之间进行比较。
高剂量波士顿组的平均左心室尺寸显著增加（观察值：预测值，4.57cm：4.45cm；P = 0.002），且显著高于两个哥本哈根组。在三个低剂量组中，平均左心室尺寸没有显著增加，且各组之间无显著差异。同样，高剂量波士顿组的平均左心室缩短分数显著降低（观察值：预测值，29.0%：33.8%；P = 0.0001），且显著低于三个低剂量组。
当累积蒽环类药物剂量≤300mg/m²时，儿童白血病治疗数年之后左心室缩短分数降低和左心室扩张并不常见。
