非血缘关系异基因骨髓移植19例临床分析

A clinical study of 19 cases of unrelated heterogenic bone marrow transplantation

目的 探讨非血缘关系异基因骨髓移植 (URD BMT)的疗效和相关合并症。方法 我所1998年 8月～ 2 0 0 1年 2月行 19例URD BMT。预处理方案 :2例以全身照射 (TBI)为主的方案 ,其余均用化疗方案。移植物抗宿主病 (GVHD)的预防 :所有患者均接受环孢素A和短程甲氨蝶呤方案。其中 7例用霉酚酸酯 (MMF) ,1例用CD3 +CD2 5,9例用抗胸腺细胞球蛋白 (ATG) ,其中 1例骨髓经免疫毒素体外去除T淋巴细胞。骨髓回输 :18例经股动脉插管输入。结果 19例中 2例因观察期尚短不能评价 ,其余 17例均植活。超急性GVHD发生 7例 ;急性GVHDⅡ～Ⅳ度为 9/ 17例 ,累积发生率为5 3 0 %。采用单因素分析表明 ,HLA配型不合、未用ATG、MMF、输入细胞数或植活时间 ,对Ⅱ～Ⅳ度急性GVHD的发生率均无显著影响。感染情况 :移植后 5周内发热的患者为 11/ 17例。在随访期内 ,10例发生巨细胞病毒感染。存活情况 :19例中死亡 6例。 18个月无病存活 5 8 3%。结论 URD BMT作为治疗恶性血液病的方法 ,因移植相关病死率较高 ,尚不能大规模开展。当高危急性白血病、慢性髓细胞白血病的患者没有合适的亲缘供者时 ,URD BMT不失为治疗的措施之一。

Objective To investigate the outcomes and problems in unrelated bone marrow transplantation (URD BMT). Methods 19 patients received URD BMT in our institute from August 1998 to February 20, 2001. The diagnoses included chronic myelogenous leukemia (CML) ( n =9), acute lymphoblastic leukemia (ALL) ( n =6), acute myelogenous leukemia(AML) ( n =2), MDS RAEB ( n =1) and β thalassemia major ( n =1). 19 pairs were HLA A,HLA B,HLA DR matched with low resolution technique ; 8 of them were HLA A?B or DRB1 mismatched with high resolution technique. 2 patients received a TBI conditioning regimen, the other 17 received BUCY or modified BUCY regimen. Bone marrow was infused to 18 recipients via aorta and one through intravenous route. As graft vesus host desease (GVHD) prophylaxis, all patients received CSA and MTX, 9 patients received ATG,1 patient received CD 3/CD 25 and 7 patients received mycophenolate mofetil . T cell depletion technique was applied in one patient. Statistics Kaplan Meier plots for time dependent analysis (survival, acute GVHD and engraft). Fisher′ exact test was used for univariate analysis of risk factors.Results Apart from 2 patients who were under observation and one patient with CML suffered from late rejection.16 out of the 19 patients had all been persistently engrafted. Relapse happened on day 60 in one patient who had advanced refractory ALL. Early infection within 5 weeks after BMT with discernable pathogens was documented in 5 patients. CMV infection occurred in 10 patients. 13 out of the 19 patients have survived. The disease free survival rate was 58.3%. The cumulative incidence of acute GVHD grades Ⅱ～Ⅳ was 53.0%. Conclusion Even if the results of using HLA identical unrelated donor marrow are encouraging, the high transplantation related mortality due to infection and GVHD is a major challenge. It is not likely that this technique will be extensively used. However, in cases of high risk acute leukemia or chronic myelogenous leukemia without appropriate related donor, URD BMT might be a therapeutic measure.