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背景:应用亲属人类白细胞抗原单倍体相合供者进行造血干细胞移植,几乎可使所有需要移植治疗的患者都能在亲属间及时找到供者。但由于人类白细胞抗原不合的免疫学障碍,应用常规方式移植不但排斥率高而且重度移植物抗宿主病发病率显著增高。目的:观察应用清髓性预处理联合多种免疫抑制方案进行非体外去T细胞的人类白细胞抗原单倍体相合外周血干细胞移植治疗恶性血液病的疗效。设计、时间及地点:病例观察,于2002-07/2008-06在新疆医科大学第一附属医院血液科,血液病研究所完成。对象:恶性血液病患者42例,年龄10～48岁。供受者人类白细胞抗原配型1个位点不合者7例,2～3个位点不合者35例。方法:预处理方案为清髓性的,预防移植物抗宿主病均以环孢素加短程甲氨蝶呤为基础方案,人类白细胞抗原1个位点不合时加用霉酚酸酯,人类白细胞抗原2～3个位点不合时再加用抗胸腺细胞球蛋白及抗CD25单抗。移植物为经粒细胞集落刺激因子动员的未进行体外去除T细胞的外周血干细胞,移植的CD34+细胞11×106/kg。主要观察指标:观察患者移植物抗宿主病发生情况及移植后1,3,6,12及18个月供、受者人类白细胞抗原相合及单倍体移植受者T、B亚群变化。结果:42例患者均获得完全、持久供者干细胞植入,发生急性移植物抗宿主病19例,Ⅰ度16例,Ⅱ度3例,2年累积发病率为50.8%;在随访大于6个月的31例患者中发生慢性移植物抗宿主病23例,局限型20例,广泛型3例,2年累积发病率为57.1%,无患者死于移植物抗宿主病。人类白细胞抗原单倍体非去T细胞外周血干细胞移植后T、B亚群下降及恢复与人类白细胞抗原相合移植无统计学差异。结论:在小样本临床治疗中,应用清髓性预处理联合多种免疫抑制剂进行非体外去T细胞亲属间人类白细胞抗原单倍体相合外周血干细胞移植治疗恶性血液病安全有效,今后需扩大样本量进一步证实其临床疗效。
Background: Hematopoietic stem cell transplantation using a haploidentical donor of human leukocyte antigen haploidentical donor almost enables all patients in need of transplantation to find a donor in time between relatives. However, due to the immunological disorder of human leukocyte antigen incompatibility, the conventional method of transplantation not only has a high rejection but also a significantly higher incidence of severe graft-versus-host disease. OBJECTIVE: To observe the curative effect of myeloablative pretreatment combined with multiple immunosuppressive regimens for the treatment of hematologic malignancies by haploidentical HSC transplantation in vitro without T cells. DESIGN, TIME AND SETTING: Case observation was performed at the Department of Hematology and Hematology, the First Affiliated Hospital of Xinjiang Medical University from July 2002 to June 2008. Subjects: 42 cases of hematological malignancies, aged 10 to 48 years old. Donor recipients of human leukocyte antigen 1 site disagreement in 7 cases, 2 to 3 sites in 35 cases. Methods: The pretreatment regimen was myeloablative and the prevention of graft versus host disease was based on cyclosporine and short-course methotrexate. One point of human leukocyte antigen was treated with mycophenolate mofetil, human leukocyte Antigen 2 to 3 sites when combined with anti-thymocyte globulin and anti-CD25 monoclonal antibody. Grafts were mobilized by granulocyte colony-stimulating factor without removal of T cells in vitro from peripheral blood stem cells, transplanted CD34 + cells 11 x 106 / kg. MAIN OUTCOME MEASURES: The incidence of graft-versus-host disease and the changes of subgroup T and B of recipients of human leukocyte antigen haploidentical and haploid recipients at 1, 3, 6, 12 and 18 months after transplantation were observed. Results: Twenty-four patients received complete and sustained donor stem cell implantation. There were 19 acute graft-versus-host disease, 16 cases with grade I and 3 cases with grade II, and the cumulative incidence at 2 years was 50.8% Thirty-one patients in the month developed chronic graft-versus-host disease in 23 cases, 20 cases in limited type and 3 cases in broad type. The cumulative incidence in 2 years was 57.1%. No patient died of graft-versus-host disease. Human leukocyte antigen haploid non-T cell peripheral blood stem cell transplantation T, B subpopulation reduction and recovery and human leukocyte antigen transplantation was no significant difference. Conclusion: It is safe and effective to treat patients with hematologic malignancies by haploidentical haploidentical haploidentical leukocyte antigen haploidentical debridement combined with multiple immunosuppressive agents in nonsmall T-cell offspring in the small sample clinical treatment. The sample size further confirmed its clinical efficacy.