Braverman A C, Antin J H, Plappert M T, Cook E F, Lee R T
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
J Clin Oncol. 1991 Jul;9(7):1215-23. doi: 10.1200/JCO.1991.9.7.1215.
Cyclophosphamide (CY) cardiotoxicity may be a lethal complication of bone marrow transplantation. Previous echocardiographic studies have reported that left ventricular dysfunction due to CY occurs in over 50% of patients undergoing transplantation. To evaluate the cardiotoxicity of new dosing protocols that included twice-daily rather than once-daily CY, 44 bone marrow transplantation patients were prospectively evaluated with serial ECGs and echocardiograms. Twenty-six patients received a once-daily lower-dose protocol (mean total 87 +/- 11 mg/kg), and 18 patients received a twice-daily higher-dose (mean total 174 +/- 34 mg/kg) CY regimen. In the higher-dose CY group, significant reductions in summed ECG voltage (-20%) (P less than .01) and increases in left ventricular mass index (LVMI) (+10%) (P less than .05) were detected in the first week following therapy. These changes resolved by the third week following CY and were significantly greater than the changes noted in the lower-dose group. However, left ventricular ejection fraction (EF) did not change significantly in either group. Five patients developed clinical cardiotoxicity (four, pericarditis; one, congestive heart failure); four of the five patients were in the higher-dose group (P = .14). Only a prior history of congestive heart failure or a baseline EF less than 50% was an independent correlate of clinical cardiotoxicity (P less than .05). Thus, dose-dependent cardiotoxicity following the use of CY for bone marrow transplantation is evident as reversible decreases in ECG voltage and increases in left ventricular mass, possibly reflecting myocardial edema or hemorrhage. However, systolic dysfunction is much less common with these new twice-daily dosing regimens when compared with earlier studies of high-dose once-daily CY.
环磷酰胺（CY）心脏毒性可能是骨髓移植的致命并发症。既往超声心动图研究报告称，接受移植的患者中超过50%会出现因CY导致的左心室功能障碍。为评估新的给药方案（包括每日两次而非每日一次的CY）的心脏毒性，对44例骨髓移植患者进行了连续心电图和超声心动图的前瞻性评估。26例患者接受每日一次的低剂量方案（平均总量87±11mg/kg），18例患者接受每日两次的高剂量（平均总量174±34mg/kg）CY方案。在高剂量CY组中，治疗后第一周检测到心电图电压总和显著降低（-20%）（P＜0.01），左心室质量指数（LVMI）增加（+10%）（P＜0.05）。这些变化在CY治疗后第三周消失，且显著大于低剂量组的变化。然而，两组的左心室射血分数（EF）均无显著变化。5例患者出现临床心脏毒性（4例为心包炎；1例为充血性心力衰竭）；5例患者中有4例在高剂量组（P = 0.14）。只有既往充血性心力衰竭病史或基线EF低于50%是临床心脏毒性的独立相关因素（P＜0.05）。因此，骨髓移植使用CY后的剂量依赖性心脏毒性表现为心电图电压可逆性降低和左心室质量增加，可能反映心肌水肿或出血。然而，与早期高剂量每日一次CY的研究相比，这些新的每日两次给药方案导致的收缩功能障碍要少见得多。
