Objective： How to reduce the incidence and severity of acute graft-versus-host disease （aGVHD） is a crucial step to improve the overall survival of allogeneic bone marrow transplantation （allo-BMT）. The low incidence of severe aGVHD observed in allogeneic peripheral blood stem cell transplantation （allo-PBSCT）, which may be related to modulating immune function of T lymphocytes by granulocyte colony-stimulating factor （G-CSF） primed donors. The study aimed to explore whether aGVHD could be alleviated by syngeneic bone marrow mixed with G-CSF-mobilized H-2 haploidentical marrow grafting. Methods： Female BALB/c mice and neonatal BALB/c mice were recipients and male （BALB/c × C57BL/6）F1（BCF1） mice were donor mice respectively. Donor mice were injected subcutaneously with G-CSF daily at 0.01 μg/g body weight or saline for 6 days, and splenocytes were harvested on day 6. Spleen index （SI） represented GVHD in neonatal mice after the intraperitoneal injection of mixed spleen cells. Lethally irradiated （^60Co, 8.5 Gy） adult mice were transplanted with a mixture of syngeneic plus G-CSF-mobilized （control diluents） H-2 haploidentical marrow cells. Survival time and survival rate of the recipients were observed after mixed marrow transplantation （MBMT）. GVHD was assessed by observing signs of weight loss, ruffled fur, diarrhea and histological change of skin, liver and small intestines. Enzyme-linked immunosorbent assay （ELISA） method was used to detect cytokines （IL-2, IL-4 and INF-γ）. Fluorescence-activated cell sorting （FACS） analysis was used to detect T cells phenotype. Results： （1） The neonatal mice subject to injection of 2：1 and 1：1 mixed spleen cells and H-2 haploidentical spleen cells all suffered from aGVHD. The severity of aGVHD in recipient mice receiving G-CSF-mobilized splenocytes was dramatically reduced. （2） The aGVHD signs and histological change were observed in most mice of 2：1 and 1：1 MBMT groups. However, the survival time of
Yihong Huang Bing Du Kailin Xu Depeng Li Qunxian Lu Xupeng He Xiuying Pan
目的:探讨降低自体骨髓移植治疗白血病的复发率的方法。方法:用自体骨髓混合半相合异基因骨髓(有核细胞量为6:1)的混合骨髓移植(mixed bone marrow transplantation,MBMT)方法治疗白血病患者4例,观察其重建造血功能情况、近期并发症、远期效果及复发率。结果:3例患者顺利重建造血功能,移植成功。1例发生急性移植物抗宿主病,因败血症于移植后14日死亡。1例移植后发生严重免疫紊乱,于移植后3个月死于肺部感染。1例移植后25个月死于复发。1例已无病存活77个月。结论:混合骨髓移植治疗白血病有一定效果,可降低自体骨髓移植治疗白血病的复发率,加强移植相关并发症的处理有望进一步提高疗效。
