单倍体造血干细胞移植治疗儿童重型再生障碍性贫血

Haploidentical Hematopoietic Stem Cell Transplantation for the Treatment of Severe Aplastic Anemia in Children

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),1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 cyclosporine（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.