Division of Hematology, University Hospital Basel, Basel, Switzerland.
Bone Marrow Transplant. 2011 Mar;46(3):344-9. doi: 10.1038/bmt.2010.137. Epub 2010 Jun 14.
BU-CY is the established non-TBI-based myeloablative conditioning regimen for allogeneic hematopoietic SCT. However, liver toxicity and hepatic veno-occlusive disease (VOD) are frequent life-threatening complications. Pharmacological considerations suggest that BU can trigger toxicity of subsequent CY. Recent animal data confirmed this hypothesis. Less liver toxicity and better outcomes were observed when mice were treated with the reversed order of CY and BU. We analyzed in this study liver toxicity and outcome in patients receiving BU-CY (16 patients) or CY-BU (59 patients). Liver function differed significantly with higher levels of liver function tests between day +10 and +30, and a higher cumulative incidence of VOD in the BU-CY cohort (2/16 (12.5%) vs 0/59 (0%), P=0.006). TRM was significantly higher in patients receiving BU-CY (cumulative incidence BU-CY 45%, CY-BU 17%, P=0.02), without yet translating into a significant survival difference (incidence for survival: BU-CY 38%, CY-BU 63%; hazard ratio 1.19 for BU-CY, 95% confidence interval 0.29-4.82, P=0.80). Rates of engraftment and relapse were not different. These data support the concepts derived from animal models in favor of CY-BU compared with traditional BU-CY and form the basis for prospective controlled comparisons.
BU-CY 是目前用于异基因造血干细胞移植的非 TBI 基础上的骨髓清除性预处理方案。但是，肝毒性和肝静脉闭塞病（VOD）是常见的危及生命的并发症。药理学考虑表明 BU 可能会引发后续 CY 的毒性。最近的动物数据证实了这一假设。当用 CY 和 BU 的相反顺序治疗小鼠时，观察到较少的肝毒性和更好的结果。我们在本研究中分析了接受 BU-CY（16 例）或 CY-BU（59 例）治疗的患者的肝毒性和结果。肝功能在第 +10 天和 +30 天之间存在显著差异，且 BU-CY 组的 VOD 累积发生率更高（2/16（12.5%）比 0/59（0%），P=0.006）。接受 BU-CY 治疗的患者的 TRM 显著更高（BU-CY 的累积发生率为 45%，CY-BU 为 17%，P=0.02），但尚未转化为显著的生存差异（生存发生率：BU-CY 为 38%，CY-BU 为 63%；BU-CY 的风险比为 1.19，95%置信区间为 0.29-4.82，P=0.80）。植入和复发率没有差异。这些数据支持了源自动物模型的概念，即与传统的 BU-CY 相比，CY-BU 更有优势，并为前瞻性对照比较奠定了基础。
