HLA配型相合的造血干细胞移植治疗重型再生障碍性贫血的临床研究

目的 评价HLA配型相合的异基因造血干细胞移植(allo-HSCT)治疗重型再生障碍性贫血(SAA)的疗效.方法 2000年1月至2008年11月采用allo-HSCT治疗SAA患者20例,其中同胞相合移植17例,非血缘关系移植3例.预处理采用环磷酰胺(Cy)50 mg·kg~(-1)·d~(-1)4 d加抗淋巴细胞免疫球蛋白(ATG)2.5 mg·kg~(-1)·d~(-1)或20 mg·kg~(-1)·d~(-1) d.移植物抗宿主病(GVHD)的预防方案为经典的环孢素A(CsA)联合短程甲氨蝶呤(MTX)及霉酚酸酯(MMF).同胞供者采集经重组人粒细胞集落刺激因子(G-CSF)动员的骨髓及外周血干细胞,非血缘供者单纯采集外周血干细胞.结果 回输单个核细胞中位数为7.89(4.00-14.21)×10~(8)/kg,所有患者均获供者造血重建,粒细胞植活中位时间14(11～20)d;血小板植活中位时间12(8～108)d.但1例患者发生晚期排斥,行另一供者二次移植后植活.21例次移植后共发生6例次急性GVHD(I度3例,Ⅱ度皮肤3例),发生率16%.19例生存期>100 d的患者中有7例发生慢性GVHD,其中4例为局限型,3例为广泛型.截至2009年2月28 日,经过中位18(2.0～106.8)个月的随访,共有17例患者无病生存,总生存率为82.5%.结论 采用Cy+ATG的预处理方案对SAA患者进行HLA配型相合HSCT,植活率高,可以获得良好的疗效.

A clinical analysis of HLA-identical hematopoietic stem cell transplantation for severe aplastic anemia

Objective To study the outcome of HLA-identical hematopoietic stem cell transplantation ( HSCT) for severe aplastic anemia (SAA). Methods Twenty patients diagnosed with SAA received allogeneic HSCT from HLA-identical donors ( 17 from siblings and 3 from unrelated donors) between January 2000 and November 2008. Conditioning regimen consisted of cyclophosphamide ( Cy) and anti-thymocyte immunoglobulin (ATG). The patients were administrated with G-CSF-primed bone marrow (G-BM) and mobilized peripheral blood (G-PB) as grafts from the sibling donors or only G-PB from the unrelated donors. Results The median infused number of mononuclear cells and CD_(34)~+ cells were 7. 89 (4-14.21) × 10~8/kg and 2.60 (0.81-4.45) × 10~6/kg. All the patients got engraftment with 100% donor chimerism. The median time of neutrophil and platelet engraftment were 14 ( 11-20) d and 12 (8-108 )d respectively. The cumulative incidence rate of acute GVHD at 100 d was 16% (grade I : 3 cases,grade II :3 cases). Chronic GVHD occurred in 7 of the 19 evaluable cases (4 limited, 3 extensive). Till February 28, 2009, with a median follow-up of 18 months, 17 patients were alive and the overall survival rate was 82. 5%. Conclusion The study confirms that using G-PB with or without G-BM as graft after Cy + ATG conditioning results in excellent outcome of HLA-identical HSCT in patients with SAA.