Department of Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Bone Marrow Transplant. 2013 Jan;48(1):26-31. doi: 10.1038/bmt.2012.114. Epub 2012 Jun 25.
We investigated the administration of i.v. BU combined with melphalan (Mel) in patients with ALL undergoing allogeneic hematopoietic SCT. Forty-seven patients with a median age of 33 years (range 20-61) received a matched sibling (n=27) or matched unrelated donor transplant (n=20) for ALL in first CR (n=26), second CR (n=13), or with more advanced disease (n=8). BU was infused daily for 4 days, either at a fixed dose of 130 mg/m² (5 patients) or using pharmacokinetic (PK) dose adjustment (42 patients), to target an average daily area-under-the-curve (AUC) of 5000 μmol/min, determined by a test dose of i.v. BU at 32 mg/m². This was followed by a rest day, then two daily doses of Mel at 70 mg/m². Stem cells were infused on the following day. The 2-year OS, PFS and non-relapse mortality (NRM) rates were 35% (95% confidence interval (CI), 23-51%), 31% (95% CI, 21-48%) and 37% (95% CI, 23-50%), respectively. Acute NRM at 100 days was favorable at 12% (95% CI, 5-24%); however, the 2-year NRM was significantly higher for patients older than 40 years, 58% vs 20%, mainly due to GVHD.
我们研究了静脉注射 BU 联合美法仑（Mel）在接受异基因造血干细胞移植的 ALL 患者中的应用。47 例中位年龄为 33 岁（范围 20-61）的患者在首次完全缓解（n=26）、第二次完全缓解（n=13）或疾病更晚期（n=8）时接受了同胞匹配（n=27）或非血缘匹配供者移植用于 ALL。BU 每日输注 4 天，固定剂量 130mg/m²（5 例）或采用药代动力学（PK）剂量调整（42 例），目标平均每日 AUC 为 5000μmol/min，通过 32mg/m² 的静脉 BU 测试剂量确定。之后休息一天，然后每日两次给予 70mg/m²的 Mel。次日输注干细胞。2 年 OS、PFS 和非复发死亡率（NRM）分别为 35%（95%CI，23-51%）、31%（95%CI，21-48%）和 37%（95%CI，23-50%）。100 天急性 NRM 为 12%（95%CI，5-24%）；然而，年龄大于 40 岁的患者 2 年 NRM 显著更高，为 58% vs 20%，主要是由于移植物抗宿主病。
