HLA单倍相合造血干细胞移植治疗恶性血液病的临床研究

Clinical study on haploid HLA-haploidentical hematopoietic stem cell transplantation for treatment of malignant hematological disease

目的探讨人类白细胞抗原(HLA)单倍相合造血干细胞移植(HSCT)治疗恶性血液病的疗效和主要并发症。方法对2004年7月至2006年12月第三军医大学附属新桥医院收治的35例恶性血液病患者进行HLA单倍相合亲缘供者HSCT。采用延长、强化联合免疫抑制促进植入、抗胸腺细胞球蛋白(ATG)加强预防移植物抗宿主病(GVHD)、粒细胞集落刺激因子(G-CSF)动员的骨髓(BM)加外周血干细胞(PBSC)混合移植方案。结果所有患者均重建供者造血。18例(51.4%)发生急性GVHD(aGVHD),其中Ⅰ度8例,Ⅱ度5例,Ⅲ度3例,Ⅳ度2例,Ⅱ～Ⅳ度aGVHD累积发生率为28.6%。12例(34.3%)发生慢性GVHD(cGVHD),均为局限性。23例患者存活,总存活率为65.7%,2年无病存活率(DFS)为62.9%。12例患者死亡,7例死于复发,5例死于移植相关合并症,其中肺部感染2例,Ⅳ度GVHD2例,巨细胞病毒(CMV)感染1例。结论随着预处理方案、GVHD预防方案及移植物成分的优化,HLA单倍相合造血干细胞移植的疗效明显改善,已成为治疗恶性血液病的重要方法。

Objective To explore the feasibility of allo-HSCT by using HLA-haploidentical donor in treatment of malignant hematological disease. Methods From July 2004 to December, thirty-five patients with malignant hematological disease in Xinqiao Hospital Third Military, Medical Universty received allo-HSCT with HLA 1,2 or 3 antigen mismatched related donors. All patients were treated with intensive immunosuppression, granulocyte colony timulating factor（G-CSF） mo- bilization,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 （CsA）, mycophenolate mofetil （ MMF）, methotrexate（ MTX ）and antithymocyte globulin （ ATG ） for graft versus host diease （ GVHD ） prophylaxis. Results All patients achieved sustained, full donor-type engraftment. Acute GVHD occurred in 18 of 35 patients. Eight of them were grade Ⅰ aGVHD,five grade Ⅱ aGVHD,three grade Ⅲ aGVHD and two grade Ⅳ aGVHD. The cumulative incidence of grade Ⅱ - Ⅳ aGVHD was 28. 6% ,chronic GVHD was observed in 12 of 35 patients and none of them developed extensive cGVHD. Twenty-three patients were alive with 65.7% two year overall survival rate and 62.9% two year disease-free survival rate. Twelve patients died ,7 from relapse and 5 from transplantation related mortality. Conclusion HLA-haploidentical HSCT is a relatively efficient method for the treatment of patients with malignant hematological disease, who have no related matched donors.