非清除性异基因骨髓移植后输注供者淋巴细胞诱导的GVHD和GVL效应  

Graft-versus-host disease and graft-versus-leukemia effect induced by infusion of donor lymphocytes after nonmyeloablative allogeneic transplantation

作　　者：杜冰[1] 徐开林[1] 潘秀英[1] 鹿群先[1] 李德鹏 居建平[1] 

机构地区：[1]徐州医学院附属医院血液科,江苏省221002

出　　处：《中华器官移植杂志》2002年第3期179-182,共4页Chinese Journal of Organ Transplantation

基　　金：江苏省卫生厅科研基金资助项目 (H9815)

摘　　要：目的　探讨非清除性异基因骨髓移植后输注逐渐增量的异基因供者淋巴细胞 ,是否能在减轻移植物抗宿主病 (GVHD)的同时保留移植物抗白血病效应 (GVL)。方法　L6 15白血病小鼠(H 2 k)为受者 ,于接种白血病细胞后的第 3d接受60 Coγ射线全身照射 ,总剂量 5Gy ,照射当天移植BALB/c小鼠 (H 2 d)的骨髓细胞 (3× 10 7个 )和脾细胞 (1× 10 7个 ) ,移植后 2d腹腔注射环磷酰胺 2 0 0mg/kg ,并分别于移植后 14d或 14、2 1、2 8d输注 2× 10 7个和 1× 10 7、2× 10 7、4× 10 7个供鼠脾细胞。结果　未处理的对照组受鼠平均存活时间为 (14 .1± 1.1)d ,均死于白血病 ;移植后未接受供鼠脾细胞组的小鼠平均存活 (2 6 .2± 3.6 )d ,均死于白血病复发 ;移植后 14d接受供鼠脾细胞输注的小鼠平均存活 (2 9.3± 3.7)d ,均死于GVHD ;移植后输注逐渐增量的供鼠脾细胞者 ,平均存活 (5 9.4± 5 .6 )d ,6 0 %的受者存活超过 5 0d ,均未发生GVHD。结论　非清除性异基因骨髓移植后输注逐渐增量的异基因供者淋巴细胞可在减轻GVHD的同时保留抗白血病效应。Objective To explore whether the graft versus host disease could be alleviated and graft versus leukemia effect be retained by infusion of escalating doses of donor lymphocytes after nonmyeloablative allogeneic bone marrow transplantation.Methods 615(H 2 k) mice were loaded with L615 cells and 3 days later received total body irradiation (TBI) of 5 Gy (60Coγ ray) followed by allogeneic bone marrow transplantation (allo BMT). The allo grafts consisted of 3×10 7 bone marrow cells and 1×10 7 spleen cells from BALB/c (H 2 d) donor mice. Two days after allo BMT, the recipient mice were given 200?mg/kg CTX intraperitoneally. Afterwards these recipient mice were infused donor spleen cells at the day of 14 or day 14, 21, 28 after transplantation, and the cells were 2×10 7 or 1×10 7,2×10 7,4×10 7 respecti vely .Results The untreated mice in the control group survived ( 14.1 ± 1.1 ) days on average and died from leukemia. After transplantation, the mice not receiving donor spleen cells survived ( 26.2 ± 3.6 ) days on average and died from the recurrence leukemia. 14 days after transplantation, the mice receiving donor spleen cells infusion survived ( 29.3 ± 3.7 ) days and died from GVHD. The mice receiving the infusion of escalating doses of donor spleen cells after transplantation survived ( 59.4 ± 5.6 ) days on average and did not suffer from GVHD.Conclusion Infusion of escalating doses of donor lymphocyte after nonmyeloablative bone marrow transplantation could reduce transplantation associated morbidity and mortality while strengthening graft versus leukemia effects.

关 键 词：骨髓移植 淋巴细胞输注 移植物抗宿主病 放射疗法 免疫活性 

分 类 号：R457.7[医药卫生—治疗学]