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

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

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）50mg·kg^-1·d^-1 4d加抗淋巴细胞免疫球蛋白（ATG）2．5mg·kg^-1·d^-1或20mg·kg^-1·d^-1。4d。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〉100d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。

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 CD34^＋ 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.