单倍型异基因造血干细胞移植治疗儿童重型再生障碍性贫血

Clinical analysis of haplotype allogeneic hematopoietic stem cell transplantation for children with severe aplastic anemia

目的 探讨单倍型异基因造血干细胞移植（allo-HSCT）治疗儿童重型再生障碍性贫血（SAA）的疗效和安全性.方法 2010年1月至2013年1月采用亲缘单倍型相合allo-HSCT治疗的16例SAA患儿.其中男10例,女6例;年龄3～13岁,平均年龄7.8岁.从确诊到移植的中位时间为15.5个月（1～ 80个月）,移植前全部接受过环孢素（CSA）治疗,接受过抗胸腺细胞球蛋白（ATG）强化免疫治疗10例.供者接受粒细胞集落刺激因子（G-CSF）动员,采用骨髓加外周血干细胞联合移植,预处理方案均采用以环磷酰胺（CTX）＋氟达拉滨（FLU）＋ ATG方案,移植物抗宿主病（GVHD）预防采用联合免疫抑制剂包括CSA、甲氨蝶呤（MTX）、他克莫司（FK506）等,移植后观察患儿的不良反应、GVHD和无病生存等情况.结果 15例患儿获造血重建,1例未植入,1例植入后发生排斥,植入的14例患儿中性粒细胞≥0.5×10^9/L及血小板≥20×10^9/L的平均时间分别为18.5d及24.6 d,植入证据检测证实100％为完全供者造血.中位随访24.8个月（3～45个月）,共6例发生急性GVHD,3例发生慢性GVHD,GVHD病死1例,感染病死2例,其余11例患儿仍无病存活,无病生存率68.8％（11/16例）.结论 单倍型allo-HSCT治疗儿童SAA的方案安全可行、疗效确切,可在临床广泛开展.

Objective To explore the efficacy and safety of haplotype allogeneic hematopoietic stem cell transplantation （allo-HSCT） in treatment of childhood severe aplastie anemia（SAA）.Methods From Jan.2010 to Jan.2013,16 children with SAA who received haploidentical allo-HSCT were studied,including 10 male and 6 female,aged from 3 to 13 years old,and the mean age was 7.8 years.The median time from diagnosis to transplantation was 15.5 months （1 to 80 months）.Before transplantation,all patients received Cyclosporin A （CSA） therapy,and 10 of them received Anti-Thymocyte Globulin（ATG） intensive immune therapy.Donors received granulocyte colony-stimulating factor （G-CSF） mobilization,and stem cell transplantation were collected from both peripheral blood and bone marrow.Cyclophosphamide （CTX） ＋ Fludarabine （FLU） ＋ ATG program was used as conditioning regimen,and combined immunosuppressive agents were used for graft-versus-host disease （GVHD） prophylaxis,including CSA,Amethopterin （MTX）,tacrolimus （FK506）,etc.Toxic and side effect,GVHD and disease-free survival of these children after transplantation were observed.Results Fifteen cases of children reached hematopoietic reconstitution,one patient had no evidence of engraftment,one showed rejection after implantation,for the 14 engrafted children with neutrophils ≥0.5 × 10^9/L and platelets ≥20 × 10^9/L,the average time was 18.5 days and 24.6 days,respectively.Implantation was confirmed by the evidence of 100% of donor hematopoiesis.With a median follow-up duration of 24.8 months （3-45 months）,6 cases developed acute GVHD,3 cases showed chronic GVHD,1 died of GVHD and 2 died of infection,the other 11 patients remained in disease-free survival,and the disease-free survival rate was 68.8% （11/16 cases）.Conclusions Haplotype allo-HSCT were safe and very effective in treatment of childhood SAA,and can be widely carried out in clinical treatment.