de Lima Marcos, Couriel Daniel, Thall Peter F, Wang Xuemei, Madden Timothy, Jones Roy, Shpall Elizabeth J, Shahjahan Munir, Pierre Betty, Giralt Sergio, Korbling Martin, Russell James A, Champlin Richard E, Andersson Borje S
Department of Blood and Marrow Transplantation, MD Anderson Cancer Center, Houston, TX 77030, USA.
Blood. 2004 Aug 1;104(3):857-64. doi: 10.1182/blood-2004-02-0414. Epub 2004 Apr 8.
Postulating favorable antileukemic effect with improved safety, we used intravenous busulfan and fludarabine as conditioning therapy for allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Fludarabine 40 mg/m2 and intravenous busulfan 130 mg/m2 were given once daily for 4 days, with tacrolimus-methotrexate as graft-versus-host disease (GVHD) prophylaxis. We treated 74 patients with AML and 22 patients with MDS; patients had a median age of 45 years (range, 19-66 years). Only 20% of the patients were in first complete remission (CR) at transplantation. Donors were HLA-compatible related (n = 60) or matched unrelated (n = 36). The CR rate for 54 patients with active disease was 85%. At a median follow-up of 12 months, 1-year regimen-related and treatment-related mortalities were 1% and 3%, respectively. Two patients had reversible hepatic veno-occlusive disease. Actuarial 1-year overall survival (OS) and event-free survival (EFS) were 65% and 52% for all patients, and 81% and 75% for patients receiving transplants in CR. Recipient age and donor type did not influence OS or EFS. Median busulfan clearance was 109 mL/min/m2 and median daily area-under-the-plasma-concentration-versus-time-curve was 4871 micromol-min, with negligible interdose variability in pharmacokinetic parameters. The results suggest that intravenous busulfan-fludarabine is an efficacious, reduced-toxicity, myeloablative-conditioning regimen for patients with AML or MDS undergoing HSCT.
假定具有良好的抗白血病效果且安全性有所提高，我们采用静脉注射白消安和氟达拉滨作为急性髓性白血病（AML）和骨髓增生异常综合征（MDS）异基因造血干细胞移植（HSCT）的预处理方案。氟达拉滨40mg/m²和静脉注射白消安130mg/m²每日给药1次，共4天，同时使用他克莫司-甲氨蝶呤预防移植物抗宿主病（GVHD）。我们治疗了74例AML患者和22例MDS患者；患者的中位年龄为45岁（范围19 - 66岁）。仅20%的患者在移植时处于首次完全缓解（CR）状态。供者为HLA相合的亲属（n = 60）或匹配的非亲属（n = 36）。54例有活动性疾病患者的CR率为85%。中位随访12个月时，1年方案相关死亡率和治疗相关死亡率分别为1%和3%。2例患者发生了可逆性肝静脉闭塞病。所有患者的1年总生存率（OS）和无事件生存率（EFS）分别为65%和52%，处于CR状态接受移植的患者分别为81%和75%。受者年龄和供者类型不影响OS或EFS。白消安的中位清除率为109mL/min/m²，血浆浓度-时间曲线下的中位每日面积为4871微摩尔·分钟，药代动力学参数的给药间期变异性可忽略不计。结果表明，静脉注射白消安-氟达拉滨对于接受HSCT的AML或MDS患者是一种有效、低毒性的清髓预处理方案。
