摘要
目的:异基因造血干细胞移植是治愈地中海贫血的唯一方法。观察应用强免疫抑制剂及胸腺球蛋白与减量的消胺为预处理方案,异基因外周血造血干细胞移植治疗重型β-地中海贫血的移植后效应以及降低并发症的特点。方法:选择2002-11于广州市第一人民医院血液科住院的11岁患者。出生时即诊断为纯合子重型β-地中海贫血。经患者家属同意和医院伦理委员会批准。对患者实施异基因外周血造血干细胞移植。供者为妹妹,血型相同,HLA配型全相合的杂合子轻型β-地中海贫血。预处理方案:氟达拉滨35mg/(m2·d),马利兰4mg/(kg·d);抗胸腺细胞球蛋白200mg/d。外周血造血干细胞动员粒细胞集落刺激因子150μg/d×7d;于移植前1d至移植后1d连续3d采集细胞总量为:CD34+3.22×106/kg,单个核细胞4.52×108/kg,CD3+T细胞22.33×107/kg,当天输注。移植物抗宿主病的预防:环孢素A联合甲基泼尼松龙并渐减量,甲基泼尼松龙在2个月内停药。采用骨髓细胞的XY/XX的荧光原位杂交和微卫星法DNA指纹图检测植入证据。结果:血小板和白细胞在移植后10,14d最低值为:1.26×109L-1,28.8×109L-1;移植后30d,血小板>50×109L-1,血红蛋白>60g/L,DNA指纹图为混合性嵌合体,性染色体示供者细胞占96%。移植后44d,血红蛋白<45g/L,XY染色体占94%,行动员供者干细胞输注,输注CD34+1.02×106/kg,单个核细胞1.20×108/kg,T细胞(CD3+)2.2×107/kg,2周后血红蛋白上升;移植后75d供者嵌合体占40%,停用环孢素A,供者嵌合体上升至96%,移植后120d,仍然为混合性嵌合体状态。无移植物抗宿主病、肝静脉闭塞病、出血性膀胱炎和感染的发生。结论:以氟达拉滨和抗胸腺细胞球蛋白强烈免疫抑制剂、减量马利兰为基础预处理方案,实施异基因外周血造血干细胞移植治疗重型β-地中海贫血,可达到造血细胞在患者体内的迅速植入,减少移植相关并发症的发生。
AIM： Allogeneic hematopoietic stem cell transplantation is the only method to treat β-thalassemia major. This study was aimed to observe the efficacy and complication of peripheral blood hematopoietic stem cell transplantation with nonmyeloablation based on fluadarabine and antithymocyte globulin for β -thalassemia major. METHODS： An eleven-year old patient was admitted at Department of Haematology, Guangzhou First People＇s Hospital in November 2002. The patient was diagnosed as having homozygote β-thalassemia major when birth. The patient and family members signed the informed consent and the experiment was approved by hospital ethics committee. Allogeneic peripheral blood hematopoietic stem cell transplantation was performed in the patient. The donor was his sister with heterozygote β-thalassemia minor. Donor-recipient human leukocyte antigen was identical and they had same red cell blood type. Conditioning regimen consisted of fluadarabine 35 mg/m2 per day, busulfan 4 mg/kg per day and antithymocyte globulin 200 mg per day. Granulocyte colony-stimulating factor-mobolized blood stem cells were collected three times from the 1st day before transplantation to the 1st day after transplantation after seven days of administration of 150 lag every day and were infused immediately. The count of cells were 3.22 × 10^6/kg of CD34＋ and 4.52 × 10^8/kg of mononuclear cells, respectively. Graft versus host disease prophylaxis consisted of cyclosporine A and methylprednisone followed reduced dosage. Methylprednisone was withdrawn within 2 months. The status of engraftment was verified by microsatellite DNA fingerprinting and fluorescence in situ hybridization of XY/XX chromatosoma. RESULTS： The lowest count of blood platelet and leukocyte were 1.26× 10^9/L^-1 and 28.8× 10^9/L^-1 10 and 14 days after transplantation, respectively. 30 days after transplantation, the count of blood platelet was over 50 × 10^9/L^-1 and haemoglobin was over 60 g/L. DNA fingerprinting and sex chromsoma showed mixed chimera of pe
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2008年第3期501-504,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
广东省医学科研课题(A2007487)~~
