非血缘关系异基因造血干细胞移植66例分析

目的对66例血液病患者进行非血缘关系异基因造血干细胞移植（allo-HSCT），探索提高移植疗效的措施。方法慢性粒细胞白血病（CML）患者24例，急性白血病（AL）患者40例，其他血液病患者2例，经预处理治疗后，进行人类白细胞抗原（HLA）基本相合的非血缘关系骨髓移植（BMT）48例，外周血干细胞移植（PBSCT）18例：部分患者采用长程加强的移植物抗宿主病（GVHD）的预防方案（将环孢菌素A提前至预处理开始时使用，同时加用霉酚酸酯）。结果64例患者达到完全稳定的供者植入，WBC植活中位时间15d（BMT组16d；PBSCT组12d，P〈0．01）。45例患者发生急性GVHD（aGVHD），累积发生率为71．16％，其中28例患者发生Ⅰ～Ⅱ度GVHD，累积发生率57．15％；17例患者发生Ⅲ～Ⅳ度GVHD，累积发生率32．25％；COX模型分析得出HLA配型及移植方式是影响aGVHD发生的因素，HLA配型相合、采用G-CSF动员的PBSCT可以降低aGVHD，尤其是重度GVHD的发生。可供分析的36例患者中有21例发生慢性GVHD。66例接受移植的患者中复发6例，死亡27例，5年的预期生存率为52．91％。用COX模型分析得出aGVHD以及aGVHD与GVHD的预防方案的交互冈素是影响生存率的惟一因素，其相对危险度分别为1.517和1.255。结论提高非血缘关系allo-HSCT疗效的关键是控制aGVHD，而选择HLA配型相合的供者，加强移植早期的免疫抑制，可以减少aGVHD的发生

Analysis of 66 cases received hematopoietic stem cell transplantation from unrelated donors

OBJECTIVE: To improve the outcome of hematopoietic stem cell transplantation from unrelated donors. METHODS: Sixty-six patients with hematological diseases (40 cases of acute leukemia, 24 chronic myeloid leukemia, and one each severe aplastic anemia and beta-thalassemia) received bone marrow (BMT, n = 48) or peripheral blood stem cell transplantation (PBSCT, n = 18) from HLA-compatible unrelated donors after BUCY or TBI conditioning. Forty patients received longer and intensive GVHD prophylaxis (cyclosporin A from day -10 combined with mycophenolate mofetil). RESULTS: Sixty-four patients achieved sustained donor engraftment. The median time of leukocyte engraftment was 15 days, being significantly earlier in PBSCT group compared with BMT group (12 vs 16 days, P = 0.002). The cumulative incidence rates of grades I-II and III-IV acute GVHD at day 100 were 57.15% and 32.25%, respectively. Chronic GVHD was seen in 21 of the 36 evaluable cases and ten of them were extensive type. Six patients relapsed and 27 dead, the overall survival at 5 years was 52.91%. The COX method analysis showed that HLA-compatible level and source of graft affected the incidence of aGVHD. The patients transplanted from HLA-matched donor with high resolution and PBSCT had the less probability for aGVHD. Patients without GVHD or with longer and intensive GVHD prophylaxis had significantly improved OS. CONCLUSION: The key to improvement the outcome of HCT from unrelated donor is to reduce the incidence and severity of aGVHD by selecting the HLA-matched donor, intensifying the immunosuppression at the early stage of transplantation.