非清髓异基因造血干细胞移植治疗14例重型再生障碍性贫血的疗效观察

Efficacy of Nonmyeloablative Allogeneic Hematopoietic Stem Cells for 14 Case of Severe Acquired Aplastic Anemia

目的:评价非清髓异基因造血干细胞移植(nonmyeloablative stem cell transplantation,NST)治疗重型再生障碍性贫血(severe acquired aplastic anemia,SAA)的疗效。方法:14例有血缘相关HLA全相合的SAA患者接受NST治疗,其中8例患者为SAA-Ⅰ型,6例为SAA-Ⅱ型。预处理方案采用氟达拉滨(FIUD)+环磷酰胺(CTX)+抗人胸腺/淋巴细胞免疫球蛋白(ATG/ALG)。移植物抗宿主病(GVHD)预防采用环孢素(Cs A)或他克莫司(FK506)联合霉酚酸酯(MMF)。结果:14例患者移植过程顺利,14例患者造血均获得快速重建,中性粒细胞绝对值>0.5×109/L中位恢复时间为移植后9 d,血小板数≥20×109/L中位恢复时间为移植后13 d;在移植后14 d均获得完全植入,且多次复查骨髓均为完全供者型;2例出现移植物抗宿主病(GVHD);1例患者在移植后70 d发生急性皮肤GVHD(Ⅰ度),1例患者于移植后1年发生慢性肝脏GVHD(Ⅰ度),给予对症治疗后好转,无1例患者发生Ⅱ度以上GVHD;9例患者出现细菌和真菌混合性感染和(或)病毒感染,中位感染时间为移植后54 d,经过对症抗感染治疗后好转,得到有效控制。中位随访54.5个月(5-144个月),12例患者现在无病存活,2例患者因肺部真菌感染死亡。结论:非清髓异基因造血干细胞移植(NST)治疗SAA安全可行,但要加强对感染的监测和防治。

Objective : To investigate the therapeutic efficacy of nonmyeloablative allogeneic hematopoietic stem cells transplantation for severe acquired aplastic anemia( SAA). Me thods: Fourteen patients with severe acquired aplastic anemia received nonmyeloablative allogeneic hematopoietic stem cells transplantation from HLA matched sibling donors,among them 8 cases were dagnosed as SAA-Ⅰ,6 cases were diagnosed as SAA-Ⅱ. The conditioning regimen consisted of fludarabine( FIUD),cyclophosphamide( CTX) and anti-thymocyte globulin( ATG / ALG). The prophylaxis for graft-versus-host disease( GVHD) was performed with cyclosporine( Cs A) combined with mycophenolate mofetil( MMF) or tacrolimus( FK506). Results: All the patients gained a quick successfully engraftment of donor hametopoietic cells. The mean recovery time for neutrophil and platelet was 9 d and 13 d respectively. All the patients have acquired a full donor chimerism before 14 d. There were only 2 cases of GVHD : one out of them was acute skin GVHD( grade I) at day 70 after transplantation and the other was chronic liver GVHD( grade Ⅰ) in 1 years after transplantation,the GVHD more than degree Ⅱ did not coccur in all patients,9 patients with bacterial and fungal mixed infection and( or) virus infection were observed,and improved after anti-infection therapy. The median follow-up time were 54. 5 months( ranged between 5-144 months),and 12 patients remain disease-free survival currently,only 2patients died of fungal infectin. Conclusion: Transplantation of nonmyeloablative allogeneic hematopoietic stem cell is safe and effective for the treatment of severe acquired aplastic,but the prevention,treatment and monitoring of infection need to be enhance.