同基因骨髓混合H-2半相合异基因骨髓移植的抗白血病效应实验研究

Experimental Study on Graft-Versus-Leukemic Effect Using Syngeneic Mixed with H-2 Haploidentical Marrow Transplantation

为了诱发自体骨髓移植(ABMT)后的移植物抗白血病(GVL)效应,提高患者的长期无病存活,研究了同基因混合H-2半相合异基因骨髓移植(MBMT)后的GVL效应以及移植物抗宿主病(GVHD)的耐受情况。通过混合脾细胞移植对新生小鼠GVHD的作用和MBMT对成年小鼠GVHD的活体观察,证实受体小鼠接受亚致死剂量放射后行同基因骨髓移植时,能够耐受1/6有核细胞量的H-2半同基因骨髓而不发生或发生轻度GVHD。比较观察混合1/6有核细胞H-2半同基因的同基因BMT的抗白血病效应。结果显示,单用同基因BMT者移植后2周皆死亡,混合组5周后仅2只死亡,预计生存率为66％,存活小鼠未观察到明显的GVHD,单纯照射组及L615白血病细胞接种组者1周内全死亡,照射后未接种白血病细胞而行同基因BMT者5周仅1只死亡,提示接受1/6量H-2半同基因骨髓细胞的同基因骨髓移植有显著的抗白血病效应(P<0.01),而不发生GVHD。这一研究为临床ABMT后诱导GVL效应,提供了一个新的途径。

In order to reduce the relapse of leukemia and improve the survival in patients after autologous bone marrow transplantation (ABMT), we studied the graft-versus-leukemia (GVL) effect of mixed syngeneic with H-2 haploidentical marrow grafting and the tolerence to graft-versus host disease (GVHD). By using of spleen enlargement of neonatal mice and mortality of sublethally irradiated adult mice after the ip injection of mixed spleen celis. The results showed that syngeneic bone marrow celis mixed with 1/6 H-2 spleen celis significantly reduced GVHD in neonatal mice, and prevented lethal GVHD in sublethally irradiated adult mice. Lethally irradiated L615(H-2k) mice were given a lethal dose of L615 leukemic celis along with syngeneic marrow or a mixture of syngeneic plus l /6 H-2 haploidentical marrow celis, the anti-leukemic effects of mixed marrow transplantation were demonstrated. This observation may have a potential to reduce the relapse of leukemia and increase the safety of clinical autologous mixed with HLA haploidentical marrow transplantation in treatment of patients with malignant blood disorders.