含氟达拉滨预处理方案对异基因造血干细胞移植过程中造血重建、移植物抗宿主病及患者生存的影响

Effect of fludarabine as a conditioning regimen on hematopoietic reconstitution,graft-versus-host disease and disease-free survival in allogeneic hematopoietic stem cell transplantation

目的:观察接受不同预处理方案改良Bucy(白消安/阿糖胞苷/环磷酰胺)或白消安/氟达拉滨对异基因造血干细胞移植后造血重建,移植物抗宿主病及生存的影响。方法:选择2006-12/2008-06解放军北京军区总医院收治的行异基因造血干细胞移植恶性血液病患者27例,按移植预处理方案不同分为两组,10例给予以氟达拉滨+白消安为基础的预处理方案:移植前2～6d氟达拉滨30mg/(m2·d),移植前3～6d白消安3.2mg/(kg·d);17例给予以改良Bucy为基础的预处理方案:移植前4～6d白消安4mg/(kg·d),移植前两三天环磷酰胺60mg/(kg·d)和阿糖胞苷2.0g/(m2·d)。比较两组患者移植后白细胞、血小板重建时间,移植物抗宿主病的发生及其程度,复发与移植相关死亡率。结果:白细胞、血小板重建时间在Bucy组与白消安/氟达拉滨组分别为[(8.45±2.31),(8.96±2.47)d,P=0.957;(13.31±4.80),(15.89±5.21)d,P=0.662]。Bucy组与白消安/氟达拉滨组患者急性移植物抗宿主病发生率分别为[47%(8/17),40%(4/10),P=0.629]。27例患者截至统计时间10例死亡,其中复发死亡4例,移植物抗宿主病死亡3例,感染死亡2例,其他移植合并症死亡1例。Bucy组与白消安/氟达拉滨组1年内总生存率分别为(58.30±19.80)%和(73.00±11.80)%,1年内无病生存率为(48.60±18.70)%和(72.20±12.80)%,白消安/氟达拉滨组总生存率及无病生存率均较Bucy组高,但两组1年内总生存率、无病生存率差异均无显著性意义(P=0.511,0.854)。结论:氟达拉滨应用于移植预处理方案中,可降低异基因造血干细胞移植过程中髓外毒性,但对疗效并无明显影响。

OBJECTIVE： To explore the effect of fludarabine on hematopoietic reconstitution, graft versus host disease （GVHD） and disease-free survival in patients who received modified Bucy or busulfan/fludarabine （Bu/Flu） conditioning regimen for allogeneic hematopoietic stem cell transplantation （allo-HSCT）, METHODS： Totally 27 patients with hematologic malignancies underwent allo-HSCT in the Beijing Military Area Command of Chinese PLA from December 2006 to June 2008 were divided into modified Bucy and Bu/Flu groups according to conditioning regimen. Ten cases received Flu/Bu regimen, 30mg/（m^2·d） at days 2-6 prior to transplantation, which increased to 3.2mg/（kg·d） at days 3-6 prior to transplantation. Seventeen cases received modified Bucy, 4mg/（kg·d） at days 4-6, increased 60mg/（kg·d） cyclophosphamide plus 2.0g/（m^2·d） cytarabine at days 2-3 prior to transplantation. The differences of haematopoietic reconstitution and GVHD between the two groups were estimated with Independent-Samples T test. Kaplan-Meier survival analysis model was used to estimate the overall survival and the disease-free survival in two groups. RESULTS： The reconstitution of white blood cell and platelet of modified Bucy group and Bu/Flu group were [（8.45±2.31）,（8.96±2.47）d, P=0.957; （13.31±4.80）,（15.89±5.21） d, P=-0.662], respectively. The incidence of acute GVHD of modified Sucy group and Bu/Flu group were [47%（8/17）,40%（4/10）, P=-0.629]. A total of 10 cases died, including 4 cases caused by recrudescence, 3 by GVHD, 2 by infection, and 1 by complication. The overall survival and the disease-free survival rate at one-year were （58.30±19.80）% and （73.00±11.80）%, （48.60±18.70）% and （72.20±12.80）% in modified Bucy and Bu/Flu groups, respectively, and the overall survival and the disease-free survival rate in Bu/Flu group were higher than that in modified Bucy group; however, there were no significantly difference between the two groups in overall survival and the disease-free survival rate （P=0.511,0.854）. CONCLUSION： Fludarabine may be used as a conditioning regimen for allogeneic hematopoietic stem cell transplantation with a lower extramedullary toxicity and almost the same efficacy.