Mavroudis D, Barrett J
Bone Marrow Transplant Unit, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Curr Opin Hematol. 1996 Nov;3(6):423-9. doi: 10.1097/00062752-199603060-00005.
Although the graft-versus-leukemia effect was predicted from animal experiments almost 40 years ago, only recently has its role in clinical bone marrow transplantation become better defined. The graft-versus-leukemia effect was initially considered to be a minor component of the graft-versus-host reaction. However, more recent analyses of clinical bone marrow transplants and the successful treatment of relapsed leukemia with donor lymphocyte transfusions indicate that the graft-versus-leukemia effect can be very powerful and to some degree independent of graft-versus-host disease. Results of donor lymphocyte transfusions draw attention to wide variability in response according to the nature of the relapsed leukemia and also to additional therapies that may enhance the efficacy of donor lymphocyte transfusions. Although natural killer lymphocytes may play a role in the graft-versus-leukemia effect, attention is focusing increasingly on T lymphocytes as potent mediators of the effect. Both CD4+ and CD8+ cells, together with the cytokines they produce, can interact with leukemia cells to deliver a cytotoxic hit on the malignant clone. Although leukemia cells undoubtedly share common antigens with other tissues of the recipient resulting in nonspecific graft-versus-host and graft-versus-leukemia reactions, there is also the possibility that distinct antigens are presented to T cells by the leukemia cells, providing a basis for separating the graft-versus-leukemia from graft-versus-host reactions. The current clinical challenge is to devise strategies for separating the graft-versus-leukemia response from graft-versus-host disease.
尽管早在近40年前的动物实验中就已预测到移植物抗白血病效应，但直到最近其在临床骨髓移植中的作用才得到更明确的界定。移植物抗白血病效应最初被认为是移植物抗宿主反应的一个次要组成部分。然而，对临床骨髓移植的最新分析以及用供体淋巴细胞输注成功治疗复发白血病表明，移植物抗白血病效应可能非常强大，并且在某种程度上独立于移植物抗宿主病。供体淋巴细胞输注的结果引起了人们对根据复发白血病的性质而产生的反应差异很大的关注，同时也关注可能增强供体淋巴细胞输注疗效的其他疗法。尽管自然杀伤淋巴细胞可能在移植物抗白血病效应中发挥作用，但人们越来越关注T淋巴细胞作为该效应的有效介导者。CD4+和CD8+细胞以及它们产生的细胞因子都可以与白血病细胞相互作用，对恶性克隆进行细胞毒性打击。尽管白血病细胞无疑与受体的其他组织共享共同抗原，从而导致非特异性的移植物抗宿主和移植物抗白血病反应，但白血病细胞也有可能向T细胞呈递独特的抗原，这为区分移植物抗白血病反应和移植物抗宿主反应提供了基础。当前的临床挑战是设计出将移植物抗白血病反应与移植物抗宿主病区分开来的策略。
