急性白血病异基因造血干细胞移植BFA/BuCyA两种预处理方案的比较

Comparing BFA with BuCyA as a Myeloablative Conditioning Regimen for Allogeneic Stem Cell Transplantation in Acute Leukemias

中文关键词:  急性白血病 异基因造血干细胞移植 氟达拉滨 预处理方案[HJ*3]

英文关键词:Acute leukemia Allogeneic stem cell transplantation Fludarabine Conditioning regimen[HJ*3]

中文摘要:

      目的 探讨氟达拉滨替换环磷酰胺整合到异基因造血干细胞移植治疗预处理方案中的疗效及安全性。方法 回顾性分析83例急性白血病患者行异基因造血干细胞移植时采用的白消安、氟达拉滨、阿糖胞苷（bulsufan，fludarabine，cytarabine，BFA）与白消安、环磷酰胺、阿糖胞苷（bulsufan，cyclophosphamide，cytarabine，BuCyA）两种预处理方案对预后的影响。BFA组53例，移植时间2009年4月至2012年8月，中位随访时间截止2012年8月为16.0月；BuCyA组30例，移植时间1999年4月至2009年4月，中位随访时间截止2012年8月为35.8月。预处理方案：BFA〔白消安 3.2 mg/（kg·d），4 d，氟达拉滨 30 mg/（m ² ·d），5 d，阿糖胞苷1 g/（m ² ·d），共5 d〕；BuCyA〔白消安 3.2 mg/（kg·d），共4 d，环磷酰胺 60 mg/（kg·d），共2 d，阿糖胞苷3 g/（m ² ·d），共2 d〕。比较观察两种预处理方案对3年无病生存率、3年复发率、急性移植物抗宿主病的发病与程度、治疗相关并发症（重症感染率、严重出血率）及死亡等的影响。结果 以BFA组随访时点为参照，与BuCyA组相应的时点比较，3年无病生存率BuCyA组40.0%，BFA组61.9%（P=0.039 9）。移植前疾病缓解者3年无病生存率在BuCyA组为44.0%，BFA组为71.6%（P=0.031 0），而移植前疾病未缓解者预期3年无病生存率BuCyA组为20.0%，BFA组为51.6%。急性移植物抗宿主病发生率BuCyA组为46.7%，BFA组为50.9%，Ⅲ-Ⅳ度急性移植物抗宿主病的发生率BuCyA组为23.3%，BFA组为9.4%。重症感染率BuCyA组为23.3%，BFA组为22.9%；严重出血率BuCyA组为26.7%，BFA为11.4%；出血性膀胱炎发生率BuCyA组为16.7%，BFA组为5.7%。结论 BFA预处理方案在急性白血病异基因造血干细胞移植中显示出明显优势，改善了患者无病生存率、降低了疾病复发率和重度急性移植物抗宿主病的发生，是一种安全有效的预处理方案。

英文摘要:

      Objective To compare BFA (busulfan, fludarabine plus cytarabine) with BuCyA (busulfan, cyclophoshpamide plus cytarabine) as the conditioning regimens in allogeneic stem cell transplantation for acute leukemias. Methods 83 patients with acute leukemia were allocated to BFA group 〔busulfan 3.2 mg/(kg·d), -9 d-6 d; fludarabine 30 mg/(m ² ·d),-5 d--1 d; cytarabine, 1 g/(m ² ·d), -5 d--1 d〕 or BuCyA group 〔busulfan, 3.2 mg/(kg·d), -8 d--5 d; cyclophoshpamide 60 mg/(kg·d),-2 d--1 d; cytarabine, 3 g/(m ² ·d),-4 d--3 d〕. Their three-year disease-free survival (DFS) rate, complete remission (CR) rate and incidences of acute graft versus host disease (aGVHD) and hemorrhagic cystitis were monitored. Results BuCyA group had lower DFS (40.0% vs 61.9%, P=0.039 9) and lower CR (44.0% vs 71.6%, P=0.031 0) than BFA group. About 20% of patients treated with BuCyA were not in remission, compared with 51.6% of those treated with BFA. aGVHD occurred in 46.7% patients in the BuCyA group and 50.9% patients in the BFA group, which were 23.3% and 9.4%, respectively, for those graded Ⅲ -Ⅳ. Severe infection occurred in 23.3% patients in the BuCyA group and 22.9% patients in the BFA group. Severe bleeding occurred in 26.7% patients in the BuCyA group and 11.4% patients in the BFA group. The incidence of hemorrhagic cystitis in the BuCyA group and BFA group was 16.7% and 5.7%, respectively. Conclusion BFA is a safer and more effective conditioning regimen compared with BuCyA.