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急性白血病自体骨髓移植后抗白血病特异性细胞毒性的体外检测

The in vitro detection of anti-leukaemia-specific cytotoxicity after autologous bone marrow transplantation for acute leukaemia.

作者信息

Lowdell M W, Ray N, Craston R, Corbett T, Deane M, Prentice H G

机构信息

Department of Haematology, Royal Free Hospital and School of Medicine, London, UK.

出版信息

Bone Marrow Transplant. 1997 May;19(9):891-7. doi: 10.1038/sj.bmt.1700756.

DOI:10.1038/sj.bmt.1700756
PMID:9156262
Abstract

Anti-leukaemia activity after allogeneic bone marrow transplantation has been studied extensively but its antigen specificity and effector cell phenotype remain unknown. Here we report a study in three recipients of autologous bone marrow transplantation done as part of the treatment for acute leukaemia, in whom we were able to detect innate specific anti-leukaemia activity post-transplant. One patient maintained selective cell-mediated cytolytic activity against her autologous leukaemic cells in the absence of cytolysis of her normal bone marrow mononuclear cells (BMMC). She remains in complete remission 3 years after ABMT for acute myeloid leukaemia (M5). A second patient was transplanted for acute lymphoblastic leukaemia and had detectable anti-leukaemia activity up to 20 weeks post-ABMT. At this point anti-leukaemia activity could no longer be demonstrated and the patient suffered a relapse 2 weeks later. A third patient was transplanted for AML (M4 Eo) and lacked detectable leukaemia-specific immune reactivity at 1, 3 and 6 months post-ABMT. She relapsed 6 months after her ABMT and returned to complete remission after further chemotherapy. She commenced treatment with alpha interferon and regained NK function. Furthermore, she developed high level cytolytic activity against her autologous leukaemic cells in the absence of activity against her remission bone marrow samples. She remains in complete remission 17 months after her initial relapse. This is the first report of an apparent association between in vitro leukaemia-specific cytolytic activity in individual patients after ABMT and clinical outcome. It encourages the theory that autologous immunomodulation may be useful in the future treatment of leukaemia.

摘要

异基因骨髓移植后的抗白血病活性已得到广泛研究,但其抗原特异性和效应细胞表型仍不清楚。在此,我们报告一项针对三名接受自体骨髓移植的急性白血病患者的研究,这是急性白血病治疗的一部分,我们能够在移植后检测到先天性特异性抗白血病活性。一名患者在对其正常骨髓单个核细胞(BMMC)无细胞溶解的情况下,维持了对其自体白血病细胞的选择性细胞介导的细胞溶解活性。她在接受急性髓系白血病(M5)自体骨髓移植3年后仍处于完全缓解状态。第二名患者接受了急性淋巴细胞白血病移植,在自体骨髓移植后20周内可检测到抗白血病活性。此时,抗白血病活性无法再被证明,该患者在两周后复发。第三名患者接受了急性髓系白血病(M4 Eo)移植,在自体骨髓移植后1、3和6个月缺乏可检测到的白血病特异性免疫反应性。她在自体骨髓移植6个月后复发,在进一步化疗后恢复完全缓解。她开始使用α干扰素治疗并恢复了自然杀伤细胞(NK)功能。此外,她在对其缓解期骨髓样本无活性的情况下,对其自体白血病细胞产生了高水平的细胞溶解活性。她在首次复发17个月后仍处于完全缓解状态。这是关于自体骨髓移植后个体患者体外白血病特异性细胞溶解活性与临床结果之间明显关联的首次报告。它支持了自体免疫调节在未来白血病治疗中可能有用的理论。

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