FLAG序贯马利兰／环磷酰胺预处理方案对异基因造血干细胞移植治疗难治／复发性急性髓系白血病疗效影响的临床观察  

Clinical outcome of allogeneic hematopoietic stem cell transplantation with FLAG sequential busulfan/cyclophosphamide conditioning regimen for refractory/relapsed acute myeloid leukemia

作　　者：刘微[1] 李渊[1] 邱志祥[1] 尹玥[1] 孙玉华[1] 许蔚林[1] 王倩[1] 梁赜隐[1] 董玉君[1] 王莉红[1] 岑溪南[1] 王茫桔[1] 王文生[1] 欧晋平[1] 任汉云[1] Liu Wei;Li Yuan;Qiu Zhixiang;Yin Yue;Sun Yuhua;Xu Weilin;Wang Qian;Liang Zeyin;Dong Yujun;Wang Lihong;Cen Xi＇nan;Wang Mangju;Wang Wensheng;Ou Jinping;Ren Hanyun(Department of Hematology,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院血液内科,100034

出　　处：《中华内科杂志》2018年第8期576-581,共6页Chinese Journal of Internal Medicine

基　　金：国家自然科学基金(81100351、81200358);教育部新教师基金(20100001120060)

摘　　要：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〉0.5×109/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〉20×109/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。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 rat

关 键 词：移植预处理 异基因造血干细胞移植 难治/复发性急性髓系白血病 FLAG方案 

分 类 号：R733.71[医药卫生—肿瘤]