非清髓异基因造血干细胞移植治疗血液病多中心临床报告

目的 研究观察我国多中心非清髓异基因造血干细胞移植(NST)治疗血液病的疗效和相关并发症.方法 我国NST协作组9个中心共243例血缘相关HLA相合的血液病患者接受了NST治疗.在FAC氟达拉滨(Flud)、抗胸腺细胞球蛋白(ATG)和环磷酰胺(CTX)]非清髓预处理方案的基础上加用阿糖胞苷或白消安等.移植物抗宿主病(GVHD)预防采用环孢素(CsA)联合霉酚酸酯(MMF)方案.结果 移植后4周供体完全植入163例(67.1%),移植失败2例(0.8%),混合植入78例(32.1%),其中56例移植后1～16个月转为完全植入,16例维持混合嵌合(MC)状态,6例移植排斥.83例(34.2%)发生急性GVHD,其中Ⅰ～Ⅱ度26例(28.9%),Ⅲ～Ⅳ度16例(6.6%);慢性GVHD 78例(32.1%).随访3～99个月,243例中仍存活162例(66.7%),其中骨髓增生异常综合征/再生障碍性贫血、慢性白血病、急性白血病首次完全缓解(CR1)和难治复发急性白血病患者的5年预期存活率分别为76.5%、73.9%、70.7%和27.8%.243例中46例(18.9%)移植后疾病复发或移植排斥.58例急性白血病CR1患者中白血病复发率为17.2%,36例难治复发急性白血病复发率为50%.结论 以FAC为基础的非清髓预处理方案有较好的耐受性和造血恢复作用,供体植入可靠,重度GVHD减少,总体生存率较高,为血液病的治疗提供了新途径.

Multicenter report of nonmyeloablative allogeneic stem cell transplantation for hematologic diseases

Objective To observe the treatment effect and toxicity of nonmyeloablative allogeneic stem cell transplantation (NST) for hematologic diseases.Methods A total of 243 hematologic diseases patients received HLA-identical NST were enrolled in this study from 9 transplant centers of NST Cooperative Group in China.Nonmyeloablative conditioning regimen was based on fludarabine(Flud),rabbit anti-human thymocyte globulin (ATG),cyclophosphamide (CTX) (FAC),and plus cytarabine or busulfan (BU) etc.Graft-versus-host disease (GVHD) prophylaxis included cyclosporin A (CsA) and mycophenolate mofetil (MMF).Results Among the 243 patients,219 (90.1%) achieved full donor chimerism (FDC),2 (0.8%) engraftment failure.78 (32.1%) had mixture chimerism(MC) at 4 weeks after NST,out of which 56 switched to FDC,16 remained MC and 6 (2.5%) developed graft rejection.The incidence of acute GVHD was 34.2%,including 6.6% of grade Ⅲ-Ⅳ acute GVHD.Chronic GVHD developed in 78 (32.1%) patients.The follow-up durations were 3-99 months,162(66.7%) were still alive and the overall survival rates were 76.5%,73.9%,70.7%,and 27.8% for MDS/SAA,chronic myeloid leukemia,acute leukemia at first remission,and refractory or relapsed leukemia,respectively.Conclusions The nonmyeloablative allogeneic stem cell transplantation based on FAC conditioning results in sustained engraftment and mild aGVHD,providing a new feasible curative therapy for hematology diseases.