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接受串联自体造血干细胞移植治疗的多发性骨髓瘤患者中高剂量环磷酰胺和美法仑的心脏毒性。

Cardiac toxicity of high-dose cyclophosphamide and melphalan in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation.

作者信息

Zver Samo, Zadnik Vesna, Černelč Peter, Koželj Mirta

机构信息

Department of Haematology, University Medical Centre Ljubljana, Zaloška 7, 1525, Ljubljana, Slovenia.

Institute of Oncology, Zaloška 2, 1525, Ljubljana, Slovenia.

出版信息

Int J Hematol. 2008 Sep;88(2):227-236. doi: 10.1007/s12185-008-0112-5. Epub 2008 Jun 12.

DOI:10.1007/s12185-008-0112-5
PMID:18548196
Abstract

Tandem autologous hematopoetic stem cell transplantation (HSCT) is an effective treatment in patients with multiple myeloma (MM). Patients receive high-dose cyclophosphamide (CY) followed by two myeloablative dosages of melphalan (MEL). Cardiotoxicity treatment related data are scanty. In 30 patients with MM chemotherapy was followed by high-dose CY (cycle CY), and two autologous tandem HSCT treatments with MEL (cycles MEL I and MEL II). During each 15-day treatment troponin I (TnI), brain natriuretic peptide (BNP) and endothelin-1 (ET-1) were controlled at six time points. All patients underwent conventional and tissue Doppler echocardiography prior to CY therapy (Eho 0), before cycle MEL I (Eho 1), before cycle MEL II (Eho 2), and 3 months after the completion of therapy (Eho 3). None of the patients developed clinical signs of heart failure. The peak TnI concentrations were noted at days 8, 11, and 15 during all three chemotherapy cycles. During all three cycles there was a significant increase in baseline BNP concentrations and BNP levels measured at day 1 after treatment with CY and MEL (CY: P = 0.0001, MEL I: P = 0.001, MEL II: P = 0.001). The highest BNP concentration occurred during CY treatment (0.517 +/- 0.391 microg/L). During cycles MEL I and MEL II we noted the peak BNP concentrations at day 4 following chemotherapy (MEL I 0.376 +/- 0.418 microg/L; MEL II 0.363 +/- 0.379 microg/L). During all three cycles the highest ET-1 levels occurred at day 1 after chemotherapy (CY 1.146 +/- 1.313 ng/L; MEL I 1.054 +/- 2.242 ng/L; MEL II 0.618 +/- 0.539 ng/L). A significant increase in ET-1 concentrations relative to the basal values occurred only in cycle MEL II (P = 0.003). The duration of wave a in the Doppler pulmonary vein flow increased significantly (Eho 0/Eho 1: P = 0.008, Eho 0/Eho 3: P = 0.026). There was a significant decrease in the A/a ratio in flow velocities during chemotherapy (Eho 0/Eho 1: P = 0.002, Eho 0/Eho 3: P < 0.0001). Early diastolic tissue Doppler velocities (Em) decreased significantly during individual cycles of chemotherapy (P = 0.006). A significant post-treatment increase in the incidence of mitral regurgitation was observed (Eho 0/Eho 3: P = 0.003). Treatment of MM patients with tandem autologous HSCT is cardiotoxic. Our patients did not develop clinically overt heart failure or myocardial necrosis. Increased plasma levels of BNP and ET-1 were compatible with transient neurohormonal activation of heart failure. Doppler echocardiography studies revealed worsening of left ventricular diastolic function and occurrence of functional mitral regurgitation.

摘要

串联自体造血干细胞移植(HSCT)是多发性骨髓瘤(MM)患者的一种有效治疗方法。患者先接受大剂量环磷酰胺(CY)治疗,随后接受两个剂量的美法仑(MEL)清髓治疗。与心脏毒性治疗相关的数据较少。在30例MM患者中,化疗后给予大剂量CY(CY周期),并进行两次MEL自体串联HSCT治疗(MEL I和MEL II周期)。在每个为期15天的治疗期间,在六个时间点监测肌钙蛋白I(TnI)、脑钠肽(BNP)和内皮素-1(ET-1)。所有患者在CY治疗前(Eho 0)、MEL I周期前(Eho 1)、MEL II周期前(Eho 2)以及治疗完成后3个月(Eho 3)均接受常规和组织多普勒超声心动图检查。所有患者均未出现心力衰竭的临床症状。在所有三个化疗周期中,TnI浓度峰值均出现在第8、11和第15天。在所有三个周期中,CY和MEL治疗后第1天测得的基线BNP浓度和BNP水平均显著升高(CY:P = 0.0001,MEL I:P = 0.001,MEL II:P = 0.001)。最高BNP浓度出现在CY治疗期间(0.517±0.391μg/L)。在MEL I和MEL II周期中,我们注意到化疗后第4天BNP浓度达到峰值(MEL I 0.376±0.418μg/L;MEL II 0.363±0.379μg/L)。在所有三个周期中,ET-1最高水平出现在化疗后第1天(CY 1.146±1.3)。

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