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生物化学标志物在白血病治疗患者心脏毒性监测中的应用。

The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia.

作者信息

Horácek J M, Pudil R, Tichý M, Jebavý L, Strasová A, Praus R, Zák P, Malý J

机构信息

2nd Department of Medicine - Clinical Hematology, University Hospital, 500 05 Hradec Králové, Czech Republic.

出版信息

Neoplasma. 2005;52(5):430-4.

Abstract

Cardiotoxicity is a serious and relatively frequent complication of anti-tumorous treatment. Anthracyclines represent the greatest risk. Biochemical markers of structural and functional myocardial damage have been gaining ground in cardiotoxicity monitoring. The aim of the study was to monitor cardiotoxicity of induction chemotherapy in acute myeloid leukemia (AML) patients and to assess the potential for use of biochemical markers in early diagnostics of cardiotoxicity. Fifteen consecutive adult patients with a newly diagnosed AML were studied. All patients received induction chemotherapy containing Idarubicin (IDA) 3 x 12 mg/m2 and intermediate doses of Cytarabine (8 x 1.5 g/m2). Serial measurements of plasma N-terminal pro brain natriuretic peptide (NT-proBNP) values were performed at the baseline, the day following each IDA infusion, after 14 days and after circa 1 month, i.e. before the next chemotherapy. Cardio-specific markers (cTnT, CK-MB mass) were measured at the baseline and after the last IDA infusion. The mean baseline value of NT-proBNP in newly diagnosed AML patients was 129.7+/-59.6 pg/ml. The mean NT-proBNP value increased after the first IDA infusion to 307.3+/-171.4 pg/ml (p=0.02). In most of the patients, the second and the third IDA infusions were not associated with a further increase in the NT-proBNP value and levels after 2 and 4 weeks were not significantly different from the baseline. However, in one of the patients the NT-proBNP values were increasing after each IDA infusion (after the last one 786.2 pg/ml) and within 14 days he developed congestive heart failure due to left ventricular diastolic dysfunction as assessed by echocardiography. At that time, the NT-proBNP value was 1,184.0 pg/ml; after diuretics it decreased significantly. In all patients, plasma cTnT and CK-MB mass concentrations were within the reference interval at the baseline and after the induction chemotherapy. Our results suggest that induction chemotherapy in AML (IDA 36 mg/m2 and intermediate doses of Cytarabine): 1. does not cause detectable damage of the myocyte structure, 2. is in all patients associated with acute neurohumoral activation (transient elevation of NT-proBNP) indicating acute subclinical cardiotoxicity, 3. may lead to congestive heart failure and NT-proBNP seems to be a promising early marker and predictor of this complication.

摘要

心脏毒性是抗肿瘤治疗中一种严重且较为常见的并发症。蒽环类药物是最大的风险因素。心肌结构和功能损伤的生化标志物在心脏毒性监测中越来越受到重视。本研究的目的是监测急性髓系白血病(AML)患者诱导化疗的心脏毒性,并评估生化标志物在心脏毒性早期诊断中的应用潜力。对15例新诊断的成年AML患者进行了连续研究。所有患者均接受包含伊达比星(IDA)3×12mg/m²和中等剂量阿糖胞苷(8×1.5g/m²)的诱导化疗。在基线、每次IDA输注后的当天、14天后以及大约1个月后(即下次化疗前),对血浆N末端脑钠肽前体(NT-proBNP)值进行系列测量。在基线和最后一次IDA输注后测量心脏特异性标志物(肌钙蛋白T(cTnT)、肌酸激酶同工酶质量(CK-MB mass))。新诊断的AML患者NT-proBNP的平均基线值为129.7±59.6pg/ml。首次IDA输注后,NT-proBNP的平均 值升至307.3±171.4pg/ml(p=0.02)。在大多数患者中,第二次和第三次IDA输注未导致NT-proBNP值进一步升高,2周和4周后的水平与基线无显著差异。然而,有一名患者每次IDA输注后NT-proBNP值均升高(最后一次输注后为786.2pg/ml),14天内他因左心室舒张功能障碍发展为充血性心力衰竭,经超声心动图评估确诊。当时,NT-proBNP值为1184.0pg/ml;使用利尿剂后显著下降。在所有患者中,基线时及诱导化疗后血浆cTnT和CK-MB mass浓度均在参考区间内。我们的结果表明,AML患者的诱导化疗(IDA 36mg/m²和中等剂量阿糖胞苷):1. 不会导致可检测到的心肌细胞结构损伤;2. 在所有患者中均与急性神经体液激活(NT-proBNP短暂升高)相关,提示急性亚临床心脏毒性;3. 可能导致充血性心力衰竭,NT-proBNP似乎是这种并发症有前景的早期标志物和预测指标。

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