单倍体造血干细胞移植治疗儿童重型再生障碍性贫血

摘要

本研究分析非体外去T细胞亲缘单倍体造血干细胞移植(hi-HSCT)治疗儿童重型再生障碍性贫血(SAA)的疗效.我院于2010年10月-2013年3月对2例SAA/极重型再生障碍性贫血(VSAA)患儿进行了非体外去T淋巴细胞的父亲2个HLA位点不合的HSCT.2例在病程4个月内用环孢素A(CsA)+粒细胞集落刺激因子(G-CSF)治疗无效,有活动或重症感染,输血依赖,无HLA全合的同胞供者或非血缘供者.移植前预处理用福达拉滨(Flu)+环磷酰胺(Cy)+抗胸腺细胞球蛋白(ATG).移植物为G-CSF动员的外周血造血干细胞(PBHSC)和骨髓(BM).移植物抗宿主病(GVHD)预防用CsA+骁悉(MMF)+短程甲氨蝶呤(MTX).结果2例患儿均达到100％供者植入,粒细胞植入时间分别为移植后12 d、18 d,血小板植入时间分别为移植后17 d、26 d.2例均出现I度急性GVHD (aGVHD),l例发展为可控制的局限性慢性GVHD(cGVHD).2年随访期间,2例患儿保持稳定的100％供者植入并有免疫功能的重建.结论:小数量临床研究结果提示在没有同胞HLA全合供者或非血缘HLA全合供者时,亲缘单倍体造血干细胞移植对儿童SAA是适宜的选择,总体生存率(OS)的提高还有待大规模前瞻性临床研究的开展.%This study was purposed to assess the effectiveness of haploidentical hematopoietic stem cell transplantation(HSCT) without in vitro T cell depletion for the treatment of severe aplastic anemia(SAA) in children.Two children with SAA/very SAA(VSAA) received T cell-depleted HSCT from their fathers with 2 loci mismatched in our center between October 2010 and March 2013.During 4 months after onset,both failed in treatment of cyelosporine(CsA) + granulocyte colony stimulating factor (G-CSF),had active or serious infections,were transfusion dependent and lacked HLA-identical sibling donors and unrelated donors.The conditioning regimen before HSCT included fludarabine,cyclophosphamide and thymoglobulin.The source of grafts was a combination of G-CSF mobilized peripheral blood hematopoietic stem cells and BM.The recipients received CsA,mycophenolate mofetil (MMF) and short-term MTX for GVHD prophylaxis.Both children with SAA achieved 100％ donor myeloid engraftment.Neutrophil engraftment occurred at day 12 and day 18 after transplant respectively.Platelet engraftment occurred at day 17 and day 26 after transplantion respectively.Two patients all developed grade I acute graft versus host disease(GVHD),one of which evolved into chronic limited GVHD well-controlled.Both have survived for two years after transplantation with 100％ donor myeloid engraftment and effective lymphoid reconstitution.In conclusion,these limited cases suggest that haploidentical HSCT for children with SAA without a HLA-identical sibling donor and unrelated donor may be feasible.Further prospective clinical study is required to increase the overall survival (OS) by decreasing GVHD while maintaining stable engraftment.