HLA单倍体相合与全相合外周血造血干细胞移植后的急性移植物抗宿主病

Acute graft-versus-host disease after compatriots HLA sibling-matched versus haploidentical allogeneic peripheral blood stem cell transplantation

背景:异基因外周血造血干细胞移植成为造血干细胞移植的主要方式,近年来HLA单倍体相合造血干细胞移植因供者来源广泛在临床应用较多,急性移植物抗宿主病仍是影响移植成功率的主要因素。目的:观察亲缘HLA单倍体相合与全相合异基因外周血造血干细胞移植后急性移植物抗宿主病的发生特点,探讨降低急性移植物抗宿主病发生率的方法及单倍体造血干细胞移植应用于临床的意义。方法:行异基因外周血造血干细胞移植的患者52例,其中HLA全相合组31例,单倍体组21例。HLA单倍体组采用改良马利兰/环磷酰胺+兔抗人胸腺T细胞免疫球蛋白预处理方案,HLA全相合组采用改良马利兰/环磷酰胺预处理方案。移植物抗宿主病的预防采用短程甲氨蝶呤+环孢素A+吗替麦考酚酯的方案。结果与结论:52例患者均获得完全持久干细胞植入。其中,急性移植物抗宿主病发病率为48%(25/52),Ⅲ-Ⅳ度急性移植物抗宿主病发病率为23%(12/52);全相合组及单倍体组急性移植物抗宿主病累积发病率分别为39%(12/31)和62%(13/21)(P>0.05);全相合组及单倍体组Ⅲ-Ⅳ度急性移植物抗宿主病累积发病率分别为10%(3/31)和43%(9/21)(P<0.05);发生于移植后+30 d、+31 d-+60 d、+61 d-+100 d的急性移植物抗宿主病类型分布差异无显著性意义(P>0.05);发生在移植后+30 d内的急性移植物抗宿主病发生率高于移植后+31 d-+60 d和+61 d-+100 d;发生急性移植物抗宿主病组和无急性移植物抗宿主病组复发率、2年无病生存率差异无显著性意义(P>0.05),全相合组与单倍体组相比复发率差异无显著性意义(P>0.05),2年无病生存率前者高于后者(P<0.05)。说明采用上述移植方案,单倍体组安全性与疗效接近全相合组;在缺乏HLA相合供者时,单倍体造血干细胞移植是治疗恶性血液病的重要方法。

BACKGROUND： In recent years, the haploidentical allogeneic peripheral blood stem cell transplantation is popular as its donor source in clinical application. Acute graft-versus-host disease is still the main factor influencing the success rate of transplantation. OBJECTIVE： To compare occurrence characteristics of acute graft-versus-host disease after compatriots HLA sibling-matched versus haploidentical allogeneic peripheral blood stem cell transplantation and to discuss the way to reduce the occurrence of acute graft-versus-host disease and the clinical significance of haploidentical allogeneic peripheral blood stem cell transplantation. METHODS： Fifty-two patients undergoing allogeneic peripheral blood stem cell transplantation were retrospectively analyzed, including 31 cases of compatriots HLA sibling-matched cell transplantation and 21 cases of haploidentical allogeneic peripheral blood stem cell transplantation. Conditioning regimen in HLA sibling-matched patients was busulfan/cyclophosphamide＋anti-thymocyte globulin for HLA sibling haploid-matched patients, and busulfan/cyclophosphamide for compatriots HLA sibling-matched patients.Short-term methotrexate＋cyclosporine A＋mycophenolate mofetil was used for prevention of graft-versus-host disease. RESULTS AND CONCLUSION： All patients successfully obtained persistent stem cell transplantation. 48% patients （12152） suffered from acute graft-versus-host disease, and 23% patients （12152） developed grade Ill-IV acute graft-versus-host disease. The cumulative incidence of acute graft-versus-host disease was 39% （12/31） in the sibling-matched group and 62% （12/21） in the sibling haploid-matched group （P 〉 0.05）. The cumulative incidence of grade Ill-IV acute greft-versus-host disease was 10% （3/31） in the sibling-matched group and 42% （9/21） in the sibling haploid-matched group （P 〈 0.05）. Type distribution of acute graft-versus-host disease occurring at 0-30 days, 31-60 days, 61-100 days after cell transplantation showed no difference （P 〉 0.05）. The incidence of acute graft-versus-host disease occurring with 30 days after transplantation was higher than those within 31-60 and 61-100 days after cell transplantation. There were no differences in recurrence rate and 2-year disease-free survival in the patients with or without acute graft-versus-host disease （P 〉 0.05）. Recurrence rate showed no difference between the sibling-matched group and sibling haploid-matched group, but the 2-year disease-free survival rate was higher in the former group （P 〈 0.05）. Therefore, HLA haploidentical transplantation is a good way to increase the source of donors for the treatment of haematological malignancies.