HLA mismatching as a strategy to reduce relapse after alternative donor transplantation
HLA mismatching as a strategy to reduce relapse after alternative donor transplantation
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DOI：
10.1053/j.seminhematol.2016.01.010
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发表时间：
2016-04-01
影响因子：
3.6
通讯作者：
Beelen, Dietrich W.
中科院分区：
文献类型：
--
作者：
Fleischhauer, Katharina;Beelen, Dietrich W.
人类白细胞抗原（HLA）错配是异位反应性T细胞的靶标，是替代供体移植后移植物抗白血病（GvL）和移植物抗宿主病（GvHD）的介质。一方面，控制GvHD的必要干预措施阻碍了利用HLA错配来减少复发，另一方面，在复发的白血病中，通过选择性丢失错配的HLA可能会导致免疫逃逸。回顾性研究报告HLA错配对移植后复发的影响需要谨慎解释，因为有许多混杂因素，包括疾病和t细胞消耗的使用，并且需要不断更新以适应快速变化的临床方案。目前的证据表明，8/ 8,7 /8 hla匹配的非相关、t细胞充满的单倍同型和脐带血移植的复发率相似；然而，在后两种情况下，对位点特异性效应的调查仍然很少。在非相关移植中，独立研究证实了HLA-C和HLA-DPB1错配以及其中基于t细胞同种异体反应性和/或表达水平定义的容许性错配在减少复发中的特定作用。这一观察结果提示了在非亲属供体搜索中利用HLA匹配的新方法，并且需要在该领域进一步研究。(C) 2016 Elsevier Inc.版权所有。
Human leukocyte antigen (HLA) mismatches are targets of alloreactive T cells, mediators of graft-versus-leukemia (GvL) and graft-versus-host disease (GvHD) after alternative donor transplantation. Exploitation of HLA mismatching in order to reduce relapse is hampered by necessary interventions aimed at controlling GvHD on the one hand, and by the possibility of immune escape through selective loss of mismatched HLA in relapsing leukemia on the other. Retrospective studies reporting the impact of HLA mismatches on post-transplant relapse need to be interpreted with caution, due to many confounding factors, including disease and use of T-cell depletion, and to be constantly updated to the rapidly changing clinical protocols. Current evidence suggests similar relapse rates for 8/8, 7/8 HLA-matched unrelated, T-cell-replete haploidentical and umbilical cord blood transplantation; however, investigations of locus-specific effects are still scarce in the latter two settings. In unrelated transplantation, a specific role for mismatches at HLA-C and HLA-DPB1, and therein of permissive mismatches defined on the basis of T-cell alloreactivity and/or expression levels, in reducing relapse has been demonstrated in independent studies. This observation suggests new approaches to utilize HLA matching in unrelated donor searches, and the need for further research in the field. (C) 2016 Elsevier Inc. All rights reserved.