静脉马利兰环磷酰胺联用预处理异基因造血干细胞移植19例

背景:由大剂量口服马利兰联合环磷酰胺组成的BuCy2是目前主要的移植前预处理方案之一,但存在较多口服马利兰相关副作用。目的:评价静脉马利兰预处理造血干细胞移植治疗恶性血液病的有效性及安全性。设计:病例观察。单位:华中科技大学同济医学院附属协和医院血液科。对象:选择2006-05/12在华中科技大学附属协和医院血液病研究所行改良静脉马利兰联用环磷酰胺为预处理方案的异基因的造血干细胞移植13例慢性粒细胞白血病患者及6例急性白血病患者,男12例,女7例,年龄14~50岁,平均33岁,其中亲缘性移植9例,非亲缘移植10例,造血干细胞来源:外周血18例,骨髓1例。所有患者及家属对治疗项目知情同意。方法:应用静脉注射马利兰组成的BuCy2预处理对患者进行异基因造血干细胞移植,即所有患者均采用目前国内外通用的改良马利兰联用环磷酰胺方案,即移植前10d口服羟基脲40mg/kg,移植前9d静脉滴注阿糖胞苷2g/m2,移植前8,7,6d应用马利兰针剂0.8mg/kg(该剂量根据既往研究与1mg/kg口服制剂等效),通过中心静脉插管由输液泵控制滴速大于2h输注完毕,1次/6h,共12次,静脉注射马利兰输注前可应用生理盐水或5%葡萄糖稀释至约0.5g/L(约稀释10倍)。移植前5,4d静脉注射环磷酰胺1.8g/(m2·d),移植前3d口服甲基环已亚硝脲250mg/m2。观察患者肝静脉闭塞病以及其他副作用的发生情况,术后进行中位6.5个月的随访观察,主要观察患者疾病复发及存活情况。主要观察指标:①移植后100d肝静脉闭塞病发生及副作用情况。②随访结果。结果:纳入患者19例均进入结果分析,术后13d内均获造血功能重建,经血型转变、染色体核型及DNA多态性证实为供者植入。①肝静脉闭塞病发生及副作用:患者在移植后100d内的肝静脉闭塞病发生率和100d时的肝静脉闭塞病相关死亡率均为0,未观察到与静脉马利兰相关的严重毒副反应。②随访结果:术后6.5个月随访,1例患者因移植后肝炎死亡,2例患者复发,其中1例经氟达拉滨 阿糖胞苷 粒细胞集落刺激因子方案化疗及供者外周血造血干细胞支持后目前已经获得完全缓解,经DNA多态性证实重新获得供者植入,另1例患者目前化疗进行中。其余患者目前均无病存活。结论:静脉马利兰的应用,可能在一定程度上减少了移植后肝静脉闭塞病的发生及其他口服马利兰相关的毒副作用,从而提高了移植疗效。

Conditioning therapy with intravenous busulfanum and cyclophosphamide for allogeneic hematopoietic stem cell transplantation: A report of 19 cases☆

BACKGROUND: BuCy2 composed of large-dose oral busulfanum and cyclophosphamide has been one of the main conditioning regimens before transplantation, but oral busulfanum can result in many side effects.OBJECTIVE: To evaluate the efficacy and safety of the conditioning regimen with intravenous busulfanum (Ⅳ Bu) in hematopoietic stem cell transplantation (HSCT) for malignant hematopathy.DESIGN: Case observation.SETTING: Department of Hematology, Union Hospital,Tongji Medical College, Huazhong University of Science and Technology.PARTICIPANTS: A total of 13 patients with chronic myelogenous leukemia (CML) and 6 patients with acute leukemia,who received allogeneic HSCT with the conditioning therapy of modified BuCy2, were enrolled at Institute of Hematopathy, Union Hospital, Huazhong University of Science and Technology from May to December 2006. There were 12 males and 7 females aged 14-50 years with an average of 33 years, and there were 9 cases of related transplantation and 10 cases of unrelated transplantation. Hematopoietic stem cells (HSCs) were harvested from peripheral blood of 18 subjects and bone marrow of 1 subject. All patients and their family members signed the informed consent.METHODS: All patients were treated with allogeneic HSCT with the conditioning therapy of intravenous BuCy2.All patients received the modified combination of busulfanum and cyclophosphamide that was commonly utilized currently.Hydroxycarbamide 40 mg/kg was orally taken ten days before transplantation. Arabinosylcytosin (Ara-C) 2 g/m2 was injected via vein nine days before transplantation. Busulfanum ampule 0.8 mg/kg (equal to 1 mg/kg oral administration)was given by central venous cannula eight, seven and six days before transplantation. The injection was performed over 2 hours controlled by infusion pump, once every 6 hours, totally 12 times. Busulfanum was diluted by saline or 5% glucose to about 0.5 g/L (about 10 times) before Ⅳ Bu. Cyclophosphamide 1.8 g/m2 was intravenously injected every day from five and four days before transplantation. Methyl-CCNU 250 mg/m2 was taken orally three days before transplantation. Occurrence of hepatic vano-occlusive disease (HVOD) and its side effects were determined. Follow-up was performed at month 6.5 after operation to observe disease recurrence and patient survival.MAIN OUTCOME MEASURES: Occurrence and side effects of HVOD 100 days after transplantation, and results of follow-up.RESULTS: Totally 19 patients were involved in the result analysis. In 13 days after transplantation, blood conversion,chromosome karyotype and DNA polymorphism tests verified that reconstruction of hematopoietic function was obtained and two patients got recurrence, of which one patient got complete remission after receiving fludarabine plus cytarabine plus granulocyte colony-stimulating factor (G-CSF) and HSCs from peripheral blood. DNA polymorhism test verified that re-engraftment was obtained. Another patient received chemotherapy. Other patients lived well.