人类白细胞抗原不相合造血干细胞移植治疗白血病的临床研究

Human leukocyte antigen mismatched hemopietic stem cell transplants for the treatment of leukemia

目的 :探讨应用人类白细胞抗原 (humanleukocyteantigen ,HLA)不相合供体造血干细胞移植治疗白血病。方法 :总结我所于 2 0 0 0年 7月至 2 0 0 1年 12月进行的 7例HLA不相合造血干细胞移植 ,其中包括 3例慢性髓性白血病、3例急性非淋巴细胞性白血病、1例急性淋巴细胞白血病。干细胞来源 :6例为外周血干细胞 ,1例为骨髓干细胞。预处理方案为改良马利兰 (busulfan ,BU) /环磷酰胺 (cyclophosphamide,CY)或BU/CY +抗胸腺细胞球蛋白 (antithymocyteglobulin ,ATG)。预防急性移植物抗宿主病 (graftversushostdisease,GVHD)采用环孢霉素A及短疗程氨甲喋呤 ,5例患者加用霉酚酸酯 (骁悉 )。结果 :1例为骨髓造血干细胞 ,采集骨髓单个核细胞数 3 .4 1× 10 8kg-1,6例为粒细胞集落刺激因子 (granlocytecolony stimulatingfactor,G CSF)动员后外周血干细胞 ,平均接受8.4 6× 10 8kg-1(4.3 0× 10 8～ 15 .3 5× 10 8kg-1)供者外周血单个核细胞 ,平均 + 13天 (+ 11～ + 16天 )中性粒细胞(absoluteneutrophilcount,ANC)大于 0 .5× 10 9L-1。平均 + 16天 (+ 11～ + 2 3天 )血小板大于 2 0 .0× 10 9L-1。发生急性Ⅰ～Ⅱ度GVHD 3例 (42 .9% ) ,无 1例严重的急性GVHD ,发生慢性广泛性GVHD 2例 (2 8.6% )。中位随访时间

Objective: To explore the feasibility of HLA mismatched hemopietic stem cell transplants for the treatment of leukemia.Methods:Between July 2000 and December 2001,seven patients received hemopietic stem cell transplants(HSCT) with HLA mismatched family donors,including 3 chronic myelocytic leukemia(CML),3 acute nonlymphocytic leukemia(ANLL),and 1 acute lymphocytic leukemia (ALL).Stem cell sources were bone marrow( n =1) or G CSF mobilized peripheral blood ( n =6). All the patients were conditioned with busulfan(BU) 12 mg·kg -1 and cyclophosphamide(CY) 3.6 g·m -2 ,of whom 4 were conditioned with additioned antithymocyte globulin(ATG).Graft versus host disease(GVHD) prophylaxis regimen consisted of cyclosporin A(CSA)、methotrexate(MTX) and mycophenolate mofetil(MMF). Results: One patients received 3.41×10 8 kg -1 mononuclear cells(MNC)from bone marrow;six patients received a mean number of 8.46×10 8 kg -1 (4.3×10 8- 15.4× 10 8 kg -1 )MNC from peripheral blood.The mean time of ANC >0.5×10 9 L -1 was day 13 (11-16), and BPC> 20.0×10 9 L -1 was day 16(11-23). All the patients got engraftmentsuccessfully and attained CR.Acute Ⅰ-Ⅱ GVHD occurred in 3(42.9%) patients,no acute Ⅲ-Ⅳ GVHD occurred and extensive chronic GVHD did in 2(28.6%) patients. All the patients were alive and well after 6-24 months' follow up.Conclusion: (1)BU/CY plus ATG appears to be an effective conditioning regimen for HLA mismatched allogenic stem cell transplants. (2) G CSF mobilized peripheral blood stem cells may be the source of stem cells even for HLA mismatched hemopietic stem cell transplants.