采用改良FC/ATG预处理方案的单倍体相合及HLA全相合造血干细胞移植治疗重型再生障碍性贫血的临床疗效分析

Hematopoietic Reconstitution and Prognosis of HLA Matched and Haploidentical Hematopoietic Stem Cell Transplantation Using Modified FC/ATG Conditioning for Treatment of Severe Aplastic Anemia

目的:探讨改良FC/ATG预处理方案用于HLA同胞全相合(MSD)、亲缘单倍体相合(HFD)造血干细胞移植(HSCT)治疗重型再生障碍性贫血(SAA)的安全性和可行性。方法:回顾性分析2011年1月至2016年6月解放军总医院第一附属医院行HSCT治疗的56例SAA患者临床资料(HFD 38例/MSD 18例),比较两种移植方式对造血重建、移植物抗宿主病(GVHD)、移植相关并发症(TRT)及总生存率(OS)的影响。改良FC/ATG预处理方案包括减低环磷酰胺(CTX)剂量(总量100 mg/kg)和给予第三方间充质干细胞输注。结果:56例行MSDHSCT或HFD-HSCT的患者全部造血重建。比较中性粒细胞植入时间(P=0.58)、血小板植入时间(P=0.61)、Ⅲ-Ⅳ度aGVHD发生率(P=0.83)、广泛性cGVHD发生率(P=0.95),重度TRT发生率(P=0.69),均显示差别无统计学意义。随访32(2-66)个月,48例存活至今,HFD-HSCT组和MSD-HSCT组1年OS率分别为86%和89%,差异无统计学意义(P=0.58)。结论:采用改良FC/ATG预处理方案的HSCT治疗SAA植入稳定、毒副作用弱,GVHD发生率低,预后良好;同时对于无MSD的SAA患者,HFD-HSCT疗效与MSD-HSCT相当,可以作为替代治疗。

Objective：To analyse the feasibility and compare differences between hematopoietic reconstitution and prognosis of patients with severe aplastic anemia（SAA） after matched sibling donor（MSD） or haploidentical family donor（HFD） hematopoietic stem cell transplantation（HSCT） using the modified FC/ATG conditioning.Methods：The clinical data of 56 patients with SAA who received HSCT in First Affiliated Hospital of Chinese PLA General Hospital from January 2011 to June 2016 were analyzed retrospectively.The hematopoietic reconstitution,graft verus host disease（GVHD）,transplantation related toxicity（TRT） and prognosis after transplantation were compared.Furthermore,the modifed conditioning FC/ATG included low-dose cyclophosphamide（total dose 100 mg/kg）,infustion of third-party donor-derived mesenchymal stem cells.Results：All 56 patients with MSD-HSCT or HFD-HSCT achieved hematopoietic reconstitution.Among them,not only the recovery of neutrophils and platelets,but also the incidences of Ⅲ- Ⅳ aGVHD,extensive cGVHD and TRT were not significantly different（the P value were 0.58,0.61,0.73,0.73 and 0.67,respectively）.After following-up for 32（2-66） months,48 patients alive well,the 1-year overall survival rates were 86%in HFD-HSCT group and 89%in MSD-HSCT group,respectively（P = 0.58）.Conclusion：After HSCT using the modifed FC/ATG conditioning,patients with SAA achieved stable engraftment,low toxicity,mild GVHD and excellent outcomes.Furthermore,the HFD-HSCT achieved comparable outcomes to MSDHSCT and may be served as an alternate therapy for patients with SAA.