人白细胞抗原不合异基因造血干细胞移植治疗难治性重型再生障碍性贫血的临床研究  

Clinical research of HLA-mismatched allogeneic hematopoietic stem cell transplantation for refractory severe aplastic anemia

作　　者：楼金星[1] 陈惠仁[1] 刘晓东[1] 郭智[1] 杨凯[1] 陈鹏[1] 何学鹏[1] 张媛[1] 刘兵[1] 

机构地区：[1]北京军区总医院血液科,100700

出　　处：《白血病．淋巴瘤》2013年第7期415-418,422,共5页Journal of Leukemia & Lymphoma

摘　　要：目的 探讨人白细胞抗原（HLA）不合供者异基因造血干细胞移植治疗难治性重型再生障碍性贫血（SAA）的可行性.方法 2008年5月至2009年9月,对7例SAA患者进行了8次移植,其中女3例,男4例,中位年龄14.5岁（1.4～29.0岁）；从确诊至移植的中位时间为13个月（5.5 ～87.0个月）；移植前均接受过1种以上的免疫抑制剂[抗胸腺细胞球蛋白（ATG）、环孢素（CsA）等]治疗3个月以上无效,完全依赖输血生存.移植前仅有2例无感染并发症,其余5例均有1个以上感染部位.预处理方案：第1例首次非血缘移植时采用环磷酰胺（CTX）加200 cGy的全身放疗,另有1例非血缘患者及1例半相合患者均采用CTX＋ATG的预处理方案,其他5例（次）患者均采用CTX＋氟达拉滨（Flu）＋ ATG方案.造血干细胞来源：非血缘全合外周血供者2例,HLA8/10相合供者1例,均来自中华骨髓库；HLA半相合供者5例（来自母亲供者3例、父亲及胞兄各1例）,均为3/6位点相合.移植物抗宿主病（GVHD）预防：自预处理开始即加用CsA及吗替麦考酚酯（MMF）；移植后短暂应用甲氨蝶呤（MTX）.结果 3例非血缘移植的患者中,1例稳定植入,2例被完全排斥,其中1例在排斥后半个月（＋50天）再次由其母亲提供髓血混合干细胞进行移植,稳定植入,已随访11个月余,血象完全恢复正常,嵌合体检查100％供者型造血.半相合移植母供子患者中,1例白细胞和血小板稳定植入,但于＋52天死于颅内真菌感染,另有1例＋3天死于肺部感染.父供子的患者＋11天死于败血症.胞兄供妹的患者到＋30天时血象无改进,2次骨髓穿刺检查均无植入倾向,家长选择放弃治疗.GVHD发生情况：植入成功者均有Ⅰ～Ⅱ度皮肤排异,但都得到有效控制.结论 对无理想供者、免疫抑制治疗失败的SAA患者,采用CTX＋Flu＋ATG预处理方案行HLA不合的异基因造血干细胞移植是一种选择,值得进一步�Objective To investigate the feasibility of HLA-mismatched allogeneic hematopoietic stem cell transplantation for refractory severe aplastic anemia （SAA）.Methods From May 2008 to September 2009,a total of 7 patients with SAA were transplanted for 8 times,including 3 females,4 males,the median age was 14.5 years old （1.4-29.0 years old）,and median duration from diagnosis to transplantation was 13 months （5.5-87.0 months）.All patients received more than one immunosuppressive therapy before transplantation for 3 months or more,depending on the blood transfusion survival.Only 2 had no pretransplantation infectious complications,the remaining 5 patients had more than one locus of infection.The conditioning regimen,one patient with unmatched transplantation received CTX＋TBI,2 used CTX＋ATG,and the remaining 5 cases were treated with CTX＋Flu＋ATG.Source of hematopoietic stem cells,3 unrelated cases were from the China Marrow Donor Program,5 HLA haploidentical cases were respectively from mother （3）,father （1）,and siblings （1）,and were identical in 3/6 loci.All cases received CsA＋MMF＋MTX as acute GVHD prophylaxis.Results The 3 cases of non-blood transplantation patients,1 was stable for 18 months,the other 2 had graft rejections with one of which was re-transplanted with her mother＇ s graft （HLA haploidentical） 50 days from the first transplantation,and had been successfully followed up for more than 18 months.Chimerism check showed 100 % of donor type blood.The remaining 4 haploidentical transplantation cases,1 stable implant died of intracranial fungal infection at ＋52 day,2 died of pulmonary infection （＋3 day） or septicemia （＋11 day）,the last one had graft rejection ＋30 day.Conclusion For patients with refractory SAA and failed immunosuppressive treatment,or having no ideal donors,treatment with CTX＋Flu＋ATG and conditioned HLA incompatible allogeneic hematopoietic stem cell transplantation may be a feasible choice,which is worthy of further exploration.

关 键 词：贫血 再生障碍性 造血干细胞移植 HLA抗原不合 长期生存 移植物抗宿主病 

分 类 号：R556[医药卫生—血液循环系统疾病]