HLA半相合造血干细胞移植治疗恶性血液病的临床观察

Clinical Study on Haploid HLA-Matched Hematopoietic Stem Cell Transplantation for Treatment of Malignant Hematological Disease

背景与目的:异基因造血干细胞移植(allogeneichematopoieticstemcelltransplantation,allo-HSCT)是目前治疗恶性血液系统疾病的最有效手段。但仅有25%～30%的患者能找到人类白细胞抗原(humanleukocyteantigen,HLA)相合的亲缘供者;在无关人群中找到相合供者的概率是1/5万～1/10万,甚至更低。若进行HLA半相合造血干细胞移植(hematopoieticstemcelltransplantation,HSCT),则有90%的患者能找到供者,本文旨在探索HLA半相合HSCT治疗恶性血液病的可行性。方法:25例恶性血液病患者进行HLA半相合(其中单倍体20例)的亲缘供者HSCT。采用延长、强化联合免疫抑制促进植入及使用抗胸腺细胞球蛋白(antithymocyteglobulin,ATG)和/或加舒莱(抗CD25单抗)加强预防移植物抗宿主病(graft-versus-hostdisease,GVHD),粒细胞集落刺激因子(granulocytecolonystimulatinfactor,G-CSF)动员的骨髓(bonemarrow,BM)或加外周血干细胞(peripheralbloodstemcell,PBSC)混合移植方案。结果:所有患者均获得造血重建及达完全供者植入。21例(21/25)发生急性GVHD(aGVHD),其中Ⅰ度8例,Ⅱ度6例,Ⅲ度2例,Ⅳ度5例(其中3例为同胞部分相合),Ⅱ～Ⅳ度和Ⅲ～Ⅳ度aGVHD累积发生率分别为48.0%和28.6%。12例(12/25)发生慢性(c)GVHD,均为局限性。16例患者无病生存,1年预计无病生存率(disease-freesurvival,DFS)为(64.00±2.98)%,1年预计总生存率(overallsurvival,OS)为(64.0±3.08)%。9例死亡,其中1例死于复发,8例死于移植相关合并症,其中肺部感染4例,Ⅳ度GVHD3例,白质脑病1例。结论:HLA配型半相合的HSCT是治疗无亲缘和无关供体全相合的高危恶性血液病的有效方法,但风险较大,需在严密监测下慎重使用。

BACKGROUND ＆ OBJECTIVE： Allogeneic hematopoietic stem cell transplantation （allo-HSCT） is the most effective method to treat malignant hematological disease. However the human leukocyte antigen （HLA）-matched sibing donors can be found for only 25%-30% patients. The probability of finding an unrelated matched donor is 1/50000-1/100000, or even lower. If we choose haploid HLA-matched hematopoietic stem cell transplantation instead, we may be able to find donors for 90% patients. Our present study was to explore the feasibility of allo-HSCT by using haploid HLA-matched donor in treatment for malignant hematological disease. METHODS. Twenty-five patients with malignant hematological disease received allo-HSCT with HLA 2 or 3 antigen mismatched related donors. All patients were treated with intensive immunosuppression, granulocyte colony stimulating factor （G-CSF） mobilization, antithymocyte globulin （ATG） and combination of bone marrow and peripheral blood stem cell transplantation. The conditioning regimen was intensified and prolonged by using the combination of cyclosporine （Cs） A, MMF, ATG and anti-CD25 antibody for graft-versus-host disease （GVHD） prophylaxis. RESULTS. All patients achieved sustained, full donortype engraftment. Acute GVHD occurred in 21 of 25 patients. Eight of them were grade Ⅰ aGVHD, six grade Ⅱ aGVHD, two grade Ⅲ aGVHD and five grade Ⅳ aGVHD. The cumulative incidence of grade Ⅱ -Ⅳ aGVHD was 48% ,and grade Ⅲ -Ⅳ aGVHD was 28.57%. Chronic GVHD was observed in 12 of 25 patients and none of them developed extensive cGVHD. Sixteen patients were alive and disease free, with 64.0±2.98% 1 year disease-free survival rate. One year overall survival rate was 64.0±3.08%. Nine patients died, 1 from relapse and 8 from transplantation related mortality. CONCLUSIONS：Haploid HLA-matched allo- HSCT is a relatively efficient method for the treatment of patients with malignant hematological disease, who have no related matched donors. Nevertheless, strict administration should be carried out since it＇s a high risk approach.