氟达拉滨联合静脉马利兰的预处理方案治疗髓系恶性血液病的临床研究

Efficacy of conditioning regimen with fludarabine and intravenous busulfan for allogeneic stem cell transplantation in myeloid leukemia

目的:评价氟达拉滨(Flu)联合静脉马利兰(Bu)的预处理方案在髓系恶性血液病患者异基因造血干细胞移植(allo-HSCT)中的疗效及静脉Bu的最佳剂量。方法:45例接受allo-HSCT的髓系恶性血液病患者,预处理方案主要采用Bu3.2mg·kg-1.d-1×2～4d,Cy40～50mg/kg×2d,Flu30mg.m-2.d-1×3d,Ara-C2g.m-2.d-1×3d,无关供者移植同时加用兔抗人血清免疫球蛋白(ATG)2.5mg/kg×4d。按静脉Bu用量进一步分为2d组17例,3d组18例,4d组10例。结果:预处理过程无严重不良事件发生,无肝静脉闭塞病(VOD)发生,Ⅱ～Ⅳ度急性移植物抗宿主病(aGVHD)9例(20%),100d移植相关死亡(TRM)1例(2.2%),3年TRM15例(33.3%),3年累计复发3例(6.7%),3年无病生存率(DFS)和3年总体生存率(OS)分别为(60.5±7.5)%和(62.2±7.2)%。与Bu2d组和3d组比较,4d组患者的慢性GVHD的发生率显著增高,TRM有增高趋势;OS显著降低,DFS有降低趋势。结论:Flu联合静脉Bu的预处理方案治疗髓系恶性血液病具有较低的髓外毒性反应和较好的耐受性,移植疗效与经典预处理方案相当。

Objective：To analyze the efficacy of conditioning regimen with fludarabine and intravenous busulfan for allogeneic stem cell transplantation （allo-HSCT） in myeloid leukemia,and to explore the best doses of i.v. Bu.Method：The clinical data of 45 cases from Jan 2005 to Mar 2008 for allo-HSCT in myeloid leukemia was analyzed retrospectively. Conditioning regimen concluded：Bu 3.2 mg·kg-1 ·d-1 ×24 d,Cy 4050 mg/kg×2 d,Flu 30 mg·m-2 ·d-1 ×3 d,Ara-C 2 g·m-2 ·d-1 ×3 d. In those cases with unrelated transplants,the conditioning regimen was combined with rabbit anti-thymic lymphocytes protein 2.5 mg·kg-1 ·d-1 ×4 d. According to the doses of i.v. Bu,3 groups were devided,including i.v. Bu for 2 days in 17 patients,for 3 days in 18 patients and for 4 days in 10 patients.Result：There were no serious regimen-related toxicity and no clinically diagnosed hepatic veno-occlusive disease （VOD）. The incidence of acute graft-versus-host disease （aGVHD） grade ⅡⅣ,d-100 regimen-related mortality （TRM）,3-yrTRM and relapse were 20%,2.2%,33.3% and 6.7%,respectively. The 3-yr disease-free survival rates （DFS） and overall survival rates （OS） were （60.5±7.5）% and （62.2±7.2）%,respectively. Compared with 2 days group and 3 days group,we founded the incidence of cGVHD and TRM were higher,DFS and OS were lower in 4 days group. Conclusion：Conditioning regimen with fludarabine and intravenous busulfan has minimal extrahematologic toxicity and good tolerance. Its antitumor activity is comparable to the standard myeloablative regimens.