Department of Stem Cell Disorders, Kansai Medical University, Moriguchi City, Osaka, Japan.
Stem Cells Dev. 2011 May;20(5):759-68. doi: 10.1089/scd.2010.0232. Epub 2010 Dec 22.
The combination of allogeneic bone marrow transplantation (allo-BMT) and donor lymphocyte infusion (DLI) is a useful method for establishing donor chimerism and preventing a relapse of leukemia/lymphoma. However, there is a risk of inducing uncontrollable fatal graft-versus-host disease (GVHD). In fact, allo-BMT plus intravenous (IV)-DLI using donor splenocytes induces fatal GVHD in recipient mice. In this study, we examined the effects of the combination of intra-bone marrow (IBM)-BMT and the subcutaneous injection of donor splenocytes (SC-DLI) on the allo-BMT system. Recipient BALB/c mice were conditioned by sublethal irradiation (5 Gy), followed by IBM-BMT plus IV-DLI or SC-DLI in C57BL/6 mice. The IV-DLI group showed better engraftment of donor hemopoietic cells than the control group (without DLI) but showed fatal GVHD. The SC-DLI group, however, showed good reconstitution and mild GVHD. These results suggest that the combination of SC-DLI and IBM-BMT promotes the reconstitution of hemopoiesis and helps reduce the risk of GVHD.
异基因骨髓移植(allo-BMT)和供者淋巴细胞输注(DLI)的联合应用是建立供者嵌合体和预防白血病/淋巴瘤复发的有效方法。然而,存在诱导不可控制的致命移植物抗宿主病(GVHD)的风险。事实上,用供者脾细胞进行 allo-BMT 加静脉内(IV)-DLI 会在受者小鼠中诱导致命的 GVHD。在这项研究中,我们研究了骨髓内(IBM)-BMT 联合皮下注射供者脾细胞(SC-DLI)对 allo-BMT 系统的影响。受体 BALB/c 小鼠经亚致死剂量照射(5 Gy)预处理,然后在 C57BL/6 小鼠中进行 IBM-BMT 加 IV-DLI 或 SC-DLI。与对照组(无 DLI)相比,IV-DLI 组供者造血细胞的植入更好,但出现致命性 GVHD。然而,SC-DLI 组造血重建良好,GVHD 轻微。这些结果表明,SC-DLI 和 IBM-BMT 的联合应用促进了造血重建,并有助于降低 GVHD 的风险。