非清除性异基因骨髓移植后输注供者淋巴细胞治疗白血病的实验研究

目的探讨非清除性异基因骨髓移植(allo-BMT)后供者淋巴细胞输注(DLI)是否能减少移植相关并发症、相关死亡和减轻移植物抗宿主病(GVHD),是否能增强移植物抗白血病(GVL)效应.方法荷L615白血病的615(H-2k)小鼠,于接种白血病细胞后第3天接受60Coγ射线全身照射(TBI,5Gy),照射当天移植供鼠BALB/c(H-2d)小鼠的骨髓细胞(3×107)和脾细胞(1×107),移植后第2天腹腔注射环磷酰胺(200mg/kg),分别于移植后第14天和第21天输注供鼠脾细胞(2×107)或移植后第14天输注经氢化可的松(HC)和环孢菌素A(CsA)处理后的供鼠脾细胞(5×107),观察其抗白血病作用.结果移植后第21天输注供鼠淋巴细胞组和移植后14天输注经HC、CsA处理后的淋巴细胞组小鼠生存期明显延长,分别为(45.1±12.8)d和＞50d,而非清除性allo-BMT组为(26.2±3.6)d,第14天输注供鼠淋巴细胞组为(29.3±3.7)d,差异有显著性(P＜0.01),且无明显GVHD发生.结论非清除性allo-BMT后早期输注经HC和CsA处理的供者淋巴细胞或延迟加用DLI可在减轻移植相关并发症的基础上,增强GVL效应,提高长期无病生存率.

Study on graft-versus-leukemia effects of donor lymphocyte infusion after nonmyeloablative allogeneic bone

OBJECTIVE: To explore the graft-versus-leukemia effects of donor lymphocyte infusion(DLI) after nonmyeloablative allogeneic bone marrow transplantation while attenuating treatment-associated morbidity, mortality and graft-versus-host disease. METHODS: 615(H-2k) mice were loaded with L615 cells and 3 days later received total body irradiation (TBI) 5 Gy (60 Co gamma-ray) followed by allogeneic bone marrow transplantation (allo-BMT). The allo-grafts consisted of 3 x 10(7) bone marrow cells and 1 x 10(7) spleen cells from BALB/c (H-2d) donor mice. Two days after allo-BMT, the recipient mice were given 200 mg/kg of CTX. Afterwards these recipient mice were infused either donor spleen cells (2 x 10(7)) on d14 and d21 or hydrocortison (HC) and cyclosporine A (CsA) treated donor spleen cells (5 x 10(7)) on d14 post-BMT. RESULTS: Survival time of mice received DLI on d21 and pretreated DLI on d14 post-BMT was longer than that of control group and d14 DLI group(P < 0.01) and without severe graft-versus-host disease. CONCLUSION: Donor lymphocyte infusion after nonmyeloablative bone marrow transplantation could reduce transplantation-associated morbidity and mortality while strengthening graft-versus-leukemia effects.