St. Jude Children's Research Hospital, Department of Pathology, MS 250, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Hum Immunol. 2022 Oct;83(10):712-720. doi: 10.1016/j.humimm.2022.03.001. Epub 2022 Mar 11.
HLA loss in hematologic malignancies is rare at diagnosis but may occur in leukemic cells at disease relapse. Although HLA mismatched hematopoietic cell transplant (HCT) is useful in exploiting graft vs. leukemia (GvL) effects, alloreactive T cells may exert immune pressure on leukemic cells, leading to immune escape. Roughly 10-30% of relapses after HLA mismatched hematopoietic cell transplant (HCT) involve loss of recipient-specific HLA genes, thereby rendering leukemic cells resistant to donor GvL effects. The use of alloreactive T cells, i.e., donor lymphocyte infusions (DLI) to control relapse following HCT will not be effective in the context of recipient-specific HLA loss and will instead carry all the risk of graft versus host disease (GvHD). Additionally, the source of the lost HLA, maternal or paternal, is important in informing the best donor choice for rescue HCT. The growing body of evidence, together with developments in laboratory testing for genomic loss of HLA, has highlighted the importance of routine testing for HLA loss in patients who relapse post HLA-mismatched HCT. Assessment of HLA loss allows transplant centers to make quick decisions regarding the most appropriate therapies and/or alternative donor selection for rescue HCT.
在血液病发病时 HLA 缺失较为罕见，但在疾病复发时白血病细胞中可能出现 HLA 缺失。尽管 HLA 不合造血细胞移植（HCT）在利用移植物抗白血病（GvL）效应方面很有用，但同种异体反应性 T 细胞可能对白血病细胞施加免疫压力，导致免疫逃逸。在 HLA 不合造血细胞移植（HCT）后约 10-30%的复发涉及受者特异性 HLA 基因丢失，从而使白血病细胞对供体 GvL 效应产生抗性。同种异体反应性 T 细胞（即供者淋巴细胞输注（DLI））在受者特异性 HLA 缺失的情况下控制 HCT 后复发将无效，反而会带来移植物抗宿主病（GvHD）的所有风险。此外，丢失的 HLA 的来源，母系或父系，对于告知用于挽救性 HCT 的最佳供体选择很重要。越来越多的证据以及 HLA 缺失的基因组检测实验室技术的发展，突显了在 HLA 错配 HCT 后复发的患者中常规检测 HLA 缺失的重要性。HLA 缺失评估使移植中心能够快速做出关于最合适治疗方法和/或替代性供体选择的决策，以进行挽救性 HCT。
