非清髓性异基因骨髓移植治疗白血病的动物实验研究  

Experimental Study on Non-myeloablative Allogeneic Bone Marrow Transplantation for Treatment of Leukemia Mice

作　　者：倪淑琴[1] 陈学良[2] 马道新[2] 张茂宏[2] 李湘新[2] 

机构地区：[1]山东省肿瘤医院,山东济南250117 [2]山东大学齐鲁医院,山东济南250012

出　　处：《肿瘤学杂志》2004年第6期382-385,共4页Journal of Chinese Oncology

摘　　要：[目的]探讨非清髓性异基因骨髓移植及加供者淋巴细胞输注治疗小鼠白血病的疗效。[方法]荷L7212白血病的615(H鄄2K)小鼠,于接种白血病细胞后第2天接受60Co鄄γ射线全身照射(TBI8.5Gy或5Gy)分为若干组,照射当天移植供鼠BALB/C(H鄄2d)小鼠的骨髓细胞(5×106)和脾细胞(1.5×107),移植后第2天腹腔注射环磷酰胺(200mg/kg);供者淋巴细胞输注组分别于移植后第7天、14天、21天再次输注供鼠脾细胞5×106、1×107、2×107,观察受鼠的移植物植入、移植物抗宿主病(GVHD)、受鼠生存时间及移植相关并发症等。[结果]非清髓性预处理能保证移植物的稳定植入,非清髓性异基因骨髓移植组小鼠生存时间为22.3±4.8天,与非清髓空白组14.7±3.4天和传统移植组18.3±3.2天比较均有显著性差异(P<0.05),供者淋巴细胞输注(DLI)组小鼠平均生存时间明显延长,为34.3±2.5天,与非清髓移植组比较均有显著性差异(P<0.05),且无明显GVHD表现和病理学改变,移植相关并发症减少。[结论]非清髓性异基因骨髓移植能在减轻GVHD的同时保留一定的移植物抗白血病(GVL)效应,移植后行DLI可在减轻移植相关并发症的基础上进一步增强GVL效应。To explore the curative effects of non-myeloablative allogeneic bone marrow transplantation for treatment of leukemia mice. Six hundred and fifteen (H-2K) mice were loaded with L7212 cells and 2 days later underwent total body irradiation(TBI) 8.5 or 5Gy(60Co γ-ray) followed by allogeneic bone marrow transplantation(allo-BMT). The allografts consisted of 5×106 bone marrow cells mixed 1.5×107 spleen cells from BALB/C (H-2d) donor mice. Two days after allo-BMT, the recipient mice were given 200mg/kg of CTX. Afterwards mice of donor lymphocyte infusions(DLI) group received 5×106, 1×107, 2×107 spleen cells from donor mice. The engrafment of allograft, graft versus host disease(GVHD), the survival days and transplantation-related complications were observed. The nonmyeloablative conditioning could ensured the engraftment of allograft, the survival days of mice in nonmyeloablative allo-BMT group were 22.3±4.8, which was much longer than that of nonmyeloablative blank group 14.7±3.4 and myeloablative group 18.3±3.2(P<0.05). There was difference between survival days of mice in DLI group and nonmyeloablative allo-BMT group (P<0.05). The mice in DLI group had no obvious GVHD signs and histological changes. Furthermore the transplantation-related complications had reduced. [Conclusions] The potential GVL effects can be preserved in nonmyeloablative while the degree of GVHD is reduced, and the method of DLI after BMT can reinforce graft versus leukemia(GVL) effects while reduce transplantation-related complications.

关 键 词：非清髓性异基因骨髓移植 移植物抗宿主病 移植物抗白血病效应 供者淋巴细胞输注 

分 类 号：R733.71[医药卫生—肿瘤]