HLA相合同胞和不全相合血缘关系供者造血干细胞移植的临床对比研究

目的 通过与HLA 6/6位点相合同胞供者异基因造血干细胞移植(allo-HSCT)的对比研究,探索HLA不全相合的血缘关系供者allo-HSCT治疗血液系统疾病的可行性.方法 30例血液系统疾病患者接受HLA 1～3个位点不合血缘关系供者allo-HSCT(HLA不合组),全部在预处理中加用兔源抗胸腺细胞球蛋白(ATG)(总量10 mg/kg,～4 d～～1 d静脉输注);28例接受HLA 6/6位点相合同胞供者HSCT(HLA相合组),5例(18%)应用ATG.两组均采用G-CSF动员十细胞和环孢素A+短程甲氨蝶呤+霉酚酸酯预防移植物抗宿主病(GVHD).结果 两组患者移植后均获得造血重建.HLA不合组与HLA相合组Ⅱ～Ⅳ度急性GVHD的累积发生率分别为34%和32%(P=0.98),Ⅲ～Ⅳ度急性GVHD的累积发生率分别为13%和11%(P=0.84).HLA不合组和HLA相合组的3年总生存(OS)率分别为57%和77%(P=0.14),3年无病生存(DFS)率分别为57%和69%(P=0.28).多因素分析显示移植前的疾病状态(P=0.006)和CMV感染(P=0.04)是影响OS的危险因素.处于疾病稳定期的患者,HLA不合组和HLA相合组的OS率相近(分别为87%和81%,P=0.65);处于疾病进展期的患者,HLA不合组的OS率明显低于HLA相合组(分别为21%和71%,P=0.02).结论 对于缺乏同胞HLA配型相合供者的疾病稳定期患者,进行HLA不全相合血缘关系供者的allo-HSCT是可行的.疾病进展期患者进行HLA不全相合血缘关系供者allo-HSCT风险性高,应通过改良预处理方案和加强移植后支持治疗以提高患者疗效.

Clinical contrasting study on hematopoietic stem cell transplantation from HLA-identical sibling and partially HLA-mismatched related donors

Objective To explore the therapeutic feasibility of allogeneie hematopeietic stem cell transplantation(allo-HSCT)from partially HLA-mismatched related donors for hematologic diseases.Methods Thirty patients with hematologic diseases received allo-HSCT from 1-3 loci mismatched related donors conditioning regimen consisting of ATG(thymoglobulin,total dose of 10 mg/kg,intravenously on-4 d to -1 d),and only 5(18%)of 28 recipients from HLA-identical sibling donors were treated with regimen containing ATG.Donors were given G-CSF prior to hematopoietic stem cell harvest and CsA,short-term MTX and mycophenolate mofetial(MMF)were used for GVHD prophylaxis in both group.Results All patients were successfully engrafted.There was no significant difference in the incidence of grade Ⅱ to Ⅳ acute graft-versus-host disease(aGVHD)and grade Ⅲ to Ⅳ aGVHD between the mismatched and matched groups (34% vs 32%,and 13% vs 11%,respectively).3-year overall survival(OS)and disease-free survival (DFS)in mismatched and matched groups were 57% vs 77%(P=0.14)and 57% vs 69%(P=0.28),respectively.Multivariate analysis showed that advanced disease pre-transplant(P=0.006)and CMV infection(P=0.04)were risk factors for OS.OS for patients with stable disease in mismatched and matched groups were 87%vs 81%(P=0.65)respectively,and for those with advanced disease were 21%f vs 71%(P=0.02).Conclusions It is feasible to perform allo-HSCT from 1-3 loci HLA-mismatched related donors for patients with stable disease who lack HLA-identical sibling donors.Nevertheless,for patients with advanced disease optimized conditioning regimen and intensive supporting therapy should be administered to obtain better clinical outcomes.