Objective: To investigate the therapeutic effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with FLAG sequential busulfan/cyclophosphamide(Bu/Cy) conditioning regimen for refractory/relapsed acute myeloid leukemia. Methods: From February 2012 to June 2017, 21 patients with refractory/relapsed acute myeloid leukemia underwent allo-HSCT with FLAG sequential Bu/Cy conditioning regimen. Transplantation-related complications and clinical outcome were retrospectively analyzed. Results: After conditioning, no hepatic veno-occlusive disease (VOD) and grade Ⅲ hemorrhagic cystitis occurred. 76.2% (16/21) patients had fever with 4 septicemia. One patient died of septic shock before engraftment. Twenty patients achieved neutrophil engraftment with a median time of 13 days (range, 10 to 21 days). Seventeen patients achieved platelet engraftment with a median time of 18 days (range, 9 to 25 days). The cumulative incidence of acute graft-versus-host disease (aGVHD) was 39.5%, and 3 patients developed grade Ⅲ-Ⅳ aGVHD. Of 19 patients who survived more than 100 days after transplantation, 4 had local chronic graft-versus-host disease (cGVHD). Of 21 patients, the median survival time was 15 months (range, 0.5 to 67 months) post-transplantation. Transplantation-related mortality rate was 28.7%. Leukemia relapse occurred in 4 patients with a median time of 4 months (range, 3 to 8 months) after transplantation. The cumulative relapse rate at 1 year was 21.4%. The 1-year and 3-year overall survival (OS) rates were 60.7% and 54.9% respectively. Log-rank analysis revealed that bone marrow blasts ≥ 20% or extramedullary leukemia before transplantation, poor platelet engraftment and grade Ⅲ-Ⅳ aGVHD were significantly related to shortened OS (P<0.05). Conclusions: Allo-HSCT with FLAG sequential Bu/Cy conditioning regimen in patients with refractory/relapsed myeloid leukemia has acceptable transplantation-related risk and relapse rate. The 1-year and 3-year OS rates are comparable with those in remission patients.
目的： 观察采用FLAG（氟达拉滨联合大剂量阿糖胞苷及重组人粒细胞集落刺激因子）序贯马利兰/环磷酰胺（Bu/Cy）预处理方案进行异基因造血干细胞移植对于难治/复发性急性髓系白血病（AML）的疗效及安全性。 方法： 对2012年2月至2017年6月北京大学第一医院21例应用FLAG序贯Bu/Cy预处理方案进行异基因造血干细胞移植的难治/复发性AML患者资料进行回顾性分析，观察移植相关合并症及疗效情况。 结果： 预处理过程中21例患者均未出现肝静脉闭塞病及Ⅲ级以上出血性膀胱炎。76.2%（16/21）患者预处理过程中出现发热，发生败血症4例，除1例因感染中毒性休克在植入前死亡外，其余患者经抗感染治疗后均好转。20例患者获得中性粒细胞植活，中性粒细胞>0.5×10(9)/L的中位时间是13（10~21）d；17例患者获得血小板植活，血小板计数>20×10(9)/L的中位时间是18（9~25）d。发生急性移植物抗宿主病8例，累积发生率为39.5%，其中3例为Ⅲ~Ⅳ度急性移植物抗宿主病。移植后存活超过100 d的19例患者中，4例出现局限性慢性移植物抗宿主病。21例患者的中位生存时间为15（0.5~67）个月，移植相关死亡率为28.7%。4例患者在移植后3~8个月出现复发，1年累积复发率为21.4%。1年和3年的总体生存率分别为60.7%和54.6%。Log-rank分析显示，移植前骨髓内原始细胞≥20%或存在髓外病变、血小板植入不良和Ⅲ~Ⅳ度急性移植物抗宿主病显著降低患者移植后的总体生存率（P<0.05）。 结论： 采用FLAG序贯Bu/Cy预处理方案的异基因造血干细胞移植具有可接受的移植相关风险，能够降低难治/复发性AML患者的复发率，提高其生存率。.
Keywords: Allogeneic hematopoietic stem cell transplantation; FLAG regimen; Refractory/relapsed acute myeloid leukemia; Transplantation conditioning.