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

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

目的通过与HLA6／6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免源抗胸腺细胞球蛋白（ATG）（总量10mg／kg，-4d～-1d静脉输注）；28例接受HLA6／6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动员干细胞和环孢素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。HIA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）。HIA不合组和HIA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0s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。

Objective To explore the therapeutic feasibility of allogeneic hematopoietic 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 graftversus-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% vs 71% （P = 0.02）. Conclusions It is feasible to perform allo-HSCT from 1 -3 loci HLA-mismatched related do- nors 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.