多种来源造血干细胞移植治疗重型再生障碍性贫血

背景：造血干细胞移植是年轻重型再生障碍性贫血患者首选方法,但在中国多数重型再生障碍性贫血患者无合适的供者,单倍体相合或非血缘造血干细胞移植国内外目前还处于探索阶段,联合间充质干细胞移植报道少见。目的：观察不同干细胞来源造血干细胞移植治疗重型再生障碍性贫血的疗效。方法：10例(3~52岁)重型再生障碍性贫血患者,分别接受了亲缘HLA相合(2例),单倍体相合(5例),非血缘(3例)的外周血和/或骨髓造血干细胞移植,其中5例患者同时联合了间充质干细胞共移植。预处理方案主要为环磷酰胺、氟达拉滨和抗人胸腺球蛋白,以霉酚酸酯、环孢素A加短疗程的甲氨蝶呤预防移植物抗宿主病,单倍体相合移植的患者在此基础上加马利兰和CD25单克隆抗体;同基因的例5患者预处理方案为抗人胸腺球蛋白+甲基泼尼龙。输注间充质干细胞的量为(0.27~1.85)×10⁶/kg。接受和未接受间充质干细胞组的患者回输的造血干细胞有核细胞分别为(7.4~17.38)×10⁸/kg和(6.09~13.68)×10⁸/kg。结果与结论：除1例单倍体相合患者移植未成功,+36 d死于并发症外,余患者移植后染色体及DNA指纹检测等说明造血干细胞移植完全供者植入。移植后中性粒细胞达到0.5×10⁹ L^-1,血小板计数≥20×10⁹ L^-1中位时间分别为12 d和13 d;其中造血功能恢复快慢的趋势是同基因移植>外周血或/和骨髓+间充质干细胞移植>单纯外周血或/和骨髓干细胞移植,而亲缘HLA全相合的52岁患者造血恢复最慢。非血缘移植例1、6患者发生了Ⅰ度急性移植物抗宿主病,单倍体相合移植的例2和例10患者发生了Ⅱ度急性移植物抗宿主病后出现了局限性的慢性移植物抗宿主病,余下患者移植后生活质量良好,无慢性移植物抗宿主病;除未接受间充质干细胞的例3患者移植后出现严重感染外,其余患者移植后再未出现严重的感染和出血。结果提示造血干细胞是安全,高效治疗重型再生障碍性贫血的方法,联合应用间充质造血干细胞者患者造血恢复快,移植并发症少。

Treatment of severe aplastic anemia with stem cells from related/unrelated and/or mesenchymal stem cell co-transplantation

BACKGROUND:Hemopoietic stem cell transplantation is the preferred method for the young patients with severe aplastic anemia (SAA), but most patients with SAA without a suitable donor in China. Haploidentical or unrelated hemopoietic stem cell transplantation is still at the exploratory stage at home and abroad, the reports addressing hemopoietic stem cell transplantation combined with mesenchymal stem cell transplantation are rare.OBJECTIVE: Toobserve the efficacy for SAA with stem cell from related/unrelated and/or hemopoietic stem cell transplantation.METHODS: A total of 10 patients aged 3-52 years with SAA were treated with related HLA-matched (n=2), haploidentical (n=5), unrelated peripheral blood and/or bone marrow hematopoietic stem cell transplantation (n=3), including 5 patients were treated with mesenchymal stem cell co-transplantation. The conditioning regimen mainly included cyclosphosphamide (CY), fludarabine (Flu), and anti-thymocyte globulin (ATG), mycophenolate mofetil, cyclosporin A and short course of methotrexate (MTX) to prevent graft-versus-host disease (GVHD). Patients with haploidentical were treated with myleran and CD25 monoclonal antibody based on the above basis. The conditioning regimen of 5 patients with homogenic is ATG + methylprednisolone. The volume of infusion of mesenchymal stem cells is (0.27-1.85)×10⁶/kg. Patients treated or not treated with mesenchymal stem cell transplantation, transfusion hematopoietic stem cells of them are nucleus cells (7.4-17.38) ×10⁸/kg and (6.09-13.68) ×10⁸/kg, respectively.RESULTS AND CONCLUSION:Except 1 case was a not successful haploidentical transplant patient and died of complications at 36 days, the chromosome and DNA fingerprint detection after transplantation in the remaining patients showed the donors completely received hematopoietic stem cell transplantation. The volume of neutrophil reached 0.5×10⁹ L^-1 after transplantation, blood platelets count ≥20×10⁹ L^-1, the median time was 12 days and 13 days. The trend of hematopoietic function recovery speed was homogenic transplantation > peripheral blood and/or bone marrow mesenchymal stem cell transplantation > simple peripheral blood and/or bone marrow stem cell transplantation, while the hematopoiesis recovery of the 52-year-old patient with related HLA-matched is the lowest. Case 1 and case 6 with unrelated peripheral blood and/or bone marrow hematopoietic stem cell transplantation suffered gradeⅠacute GVHD, case 2 and case 10 with haploidentical transplantation suffered circumscribed chronic GVHD after gradeⅡ acute GVHD, the quality of life in the remaining patients is good after transplantation, without chronic GVHD. In addition to case 3 suffered severe infection who was not received mesenchymal stem cell transplantation, the remaining patients were not suffered severe infection and hemorrhage after transplantation. The results suggested that hematopoietic stem cells are safe and effective treatment of refractory severe aplastic anemia, which combined with mesenchymal hematopoietic stem cells, rapid hematopoietic recovery and few transplant complications in patients.