FABC预处理方案同胞异基因造血干细胞移植治疗成人高危急性淋巴细胞白血病

目的:探讨以FABC预处理进行同胞异基因造血干细胞移植治疗成人高危急性淋巴细胞白血病(ALL)的疗效及相关临床预后因素。方法:2004年8月至2010年8月期间,广东省人民医院采用FABC预处理方案(氟达拉滨联合阿糖胞苷,马法兰,环磷酰胺,足叶乙甙或替尼泊甙)治疗23例成人高危ALL患者,应用Kaplan-Meier法及Cox回归模型进行生存及预后分析。结果:所有患者均于+14～+21d获完全供者植入,骨髓获CR或CRi,中性粒细胞和血小板植活中位时间分别为12(4～43)d和12(5～44)d;aGVHD及cGVHD累积发生率分别为47.8%和84.2%。中位随访21(4.4～70.5)个月,移植相关死亡率为21.7%(5/23),复发率为17.4%(4/23);死亡(8/23)原因:复发3例,肺部真菌感染2例,移植相关性微血管病、巨细胞病毒肺炎和cGVHD各1例。3年的预期总生存率和无病生存率(DFS)分别是(54.4±14.6)%和(51.9±14.1)%。预后分析显示:cGVHD是DFS独立有利因素,其相对危险度为0.062(95%可信区间0.007～0.584,P=0.015)。结论:FABC预处理同胞异基因造血干细胞移植是治疗成人高危ALL安全有效的方法,cGVHD是长期无病生存的独立有利因素。

Efficacy of allogeneic hematopoietic stem cell transplantation by FABC conditioning regimen for adult high-risk acute lymphoblastic leukemia

Objective To investigate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) by FABC conditioning regimen for adult patients with high-risk acute lymphoblastic leukemia (ALL). Methods Twenty-three patients with high-risk ALL underwent allo-HSCT with novel FABC conditioning regimen which consisted of fludarabine, cytarabine, busulfan, cyclophosphamide plus etoposide or teniposide. Overall survival (OS) and disease free survival (DFS) were analyzed using Kaplan-Meier method and Cox regression model. Results All of these patients attained full donor engraftment at day 21 post-transplantation, and achieved a CR or CRi (without complete count recovery). The median time of ANC and PLT engraftment was about +12 (4 to 43) days and +12 (5 to 44) days, respectively. The cumulative incidence of aGVHD and cGVHD was 47.8% and 84.2%, respectively. During a median follow-up duration of 21(4.4 to 70.5) months post transplantation, the incidence of TRM was 21.7% and the relapse rate was 17.4%. Three of eight patients died of relapse, one died of sever fungal pneumonia within +100 days, and the others died of TAM, CMV pneumonia and fungal infection or cGVHD. Three- year probability of OS and DFS was (54.4 ± 14.3)% and (51.9 ± 14.1)%, respectively. Based on multivariate analysis, cGVHD was the most important independent favorable factors associated with DFS (HR, 0.062; 95% CI, 0.007 to 0.584; P = 0.011). Conclusions Allo-HSCT by conditioning regimen with FABC may be a safe and effective option for adult high-risk ALL patients, and the development of chronic GVHD plays an important role of in reducing relapse and improving DFS.