马利兰和氟达拉滨与马利兰和环磷酰胺预处理方案在急性髓性白血病异基因造血干细胞移植中的比较

 目的 比较马利兰（Bu）和氟达拉滨（Flu）组成的预处理方案（Bu/Flu）与Bu和环磷酰胺（Cy）组成的预处理方案（Bu/Cy）在急性髓性白血病第一次完全缓解（AML-CR1）患者异基因造血干细胞移植（allo-HSCT）中的移植相关毒性和疗效的差异。方法 32例接受allo-HSCT的AML-CR1患者按移植顺序交替分至Bu/Cy组（Bu 3.2 mg·kg^-1·d^-1，移植前第7~4天；Cy 60 mg·kg^-1·d^-1，移植前第3~2天）或Bu/Flu组（Bu 3.2 mg·kg^-1·d^-1，移植前第5～2天；Flu 30 mg·m^-2·d^-1,移植前第6～2天）。评价两组预处理相关毒性（RRT）、移植物抗宿主病（GVHD）发生率与严重程度、3年累积复发率、非复发死亡率（NRM）、3年无病生存（EFS）率和总生存（OS）率等方面的差异。结果 中位随访时间为617.5（6~1261）d。两组中性粒细胞和血小板中位重建时间无明显差异（P=0.121和P=0.171），移植后30 d嵌合状态分析提示两组患者均达到完全植入。Bu/Cy组预处理后中性粒细胞持续<0.1×10⁹/L和血小板持续﹤20×10⁹/L中位时间明显长于Bu/Flu组［6（3~14）d比2.5（1~9）d，P=0.000；3（1~36）d比1（0~4）d，P=0.047］。Bu/Cy组与Bu/Flu组Ⅱ～Ⅳ度RRT发生率分别为68.8%和25.0%（P=0.032）；急性GVHD发生率分别为46.7%和75.0%（P=0.149），慢性GVHD发生率分别为46.7%和80.0%（P=0.149）；NRM分别为25.0%和6.3%（P=0.333）；3年累积复发率分别为（17.9±11.7）%和（14.1±9.3）%（P=0.834）；3年EFS率分别为（65.5±12.7）%和（80.2±10.3）%（P=0.362）；3年OS率分别为（68.8±11.6）%和（87.5±8.3）%（P=0.111）。结论 Bu/Flu是一种清髓性预处理方案，与Bu/Cy方案比较具有低骨髓抑制毒性及RRT。Bu/Flu作为AML-CR1患者allo-HSCT预处理方案其疗效不低于Bu/Cy。

A comparison of toxicity and efficacy between busulfan plus fludarabine and busulfan plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

Objective To compare the transplant-related toxicity and the efficacy of busulfan/fludarabine (Bu/Flu) and busulfan/cyclophosphamide (Bu/Cy) as conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia(AML) in the first complete remission (CR1).Methods Totally 32 AML-CR1 patients underwent allo-HSCT were divided into Bu/Cy (Bu 3.2 mg·kg^-1·d^-1, 7-4 days before transplantation; Cy 60 mg·kg^-1·d^-1, 3-2 days before transplantation) and Bu/Flu (Bu 3.2 mg·kg^-1·d^-1, 5-2 days before transplantation; Flu 30 mg·m^-2·d^-1, 6-2 days before transplantation) groups. The regimen-related toxicity (RRT), incidence and severity of graft-versus-host disease (GVHD), 3-year cumulative relapse rate, non-relapse mortality (NRM), 3-year event-free survival (EFS) rate and overall survival (OS) rate were compared between the two groups.Results The median follow-up duration was 617.5 (6-1261) days. All patients achieved successful engraftment on 30 day after transplantation. There were no significant differences in the median time to neutrophil engraftment (P=0.121) and platelet engraftment (P=0.171) between the two groups. The median duration of neutrophil count under 0.1×10⁹/L and platelet count under 20×10⁹/L in the Bu/Cy group were significantly longer than those in the Bu/Flu group (P=0.000 and P=0.047).The incidence of grades Ⅱ-Ⅳ RRT were 68.8% and 25.0% (P=0.032) in the Bu/Cy and the Bu/Flu groups, respectively. There were no significant differences in the incidence of acute GVHD (P=0.149), chronic GVHD (P=0.149), incidence of NRM (P=0.333), 3-year cumulative relapse rates (P=0.834), 3-year EFS rate (P=0.362) and OS rate (P=0.111) between the two groups.Conclusion Compared with Bu/Cy, Bu/Flu is a myeloablative condition regimen with milder bone marrow suppression and lower RRT incidence rate in allogeneic HSCT for AML-CR1 patients without compromising the efficacy.