The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors
The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors
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DOI：
10.1182/blood.v99.11.4200
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发表时间：
2002-06-01
期刊：
影响因子：
20.3
通讯作者：
Kodera, Y
中科院分区：
文献类型：
--
作者：
Morishima, Y;Sasazuki, T;Kodera, Y
为了改善非亲属供体异体造血干细胞移植的临床结果，鉴定与移植物抗宿主病（GVHD）、移植失败和移植物抗白血病效应等免疫事件有关的人类白细胞抗原（HLA）等位基因至关重要。回顾性地对1298对供者-患者进行HLA-A、-B、-C、-DRB1和-DQB1的基因组分型，其中骨髓来自血清学上符合HLA-A、-B和-DR的供者。HLA- a、-B、-C或-DRB1等位基因的单一差异是急性GVHD的独立危险因素，HLA-C等位基因与其他HLA等位基因错配对急性GVHD的协同作用显著。发现HLA-A和/或HLA-B等位基因错配是慢性GVHD发生的重要因素。HLA I类（A、B和/或C）等位基因不匹配导致移植失败的发生率明显高于HLA匹配。HLA-C等位基因失配与白血病复发无显著相关性。作为这些事件的结果，HLA-A和/或HLA-B等位基因错配显著降低了标准风险和高风险白血病病例的总生存率，而HLA-C错配或hla - 11类（DRB1和/或DQB1）错配则没有。此外，发现HLA位点的多重错配会降低白血病患者的生存率，从而阐明了HLA I类等位基因在非相关骨髓移植中的作用。值得注意的是，HLA-C等位基因与HLA-A或-B等位基因在急性GVHD和生存中的模式不同。(C) 2002年由美国血液病学会出版。
To improve the clinical outcome of allogeneic hematopoietic stem cell transplantation from an unrelated donor, the identification of human leukocyte antigen (HLA) alleles responsible for immunologic events such as graft-versus-host disease (GVHD), engraftment failure, and graft-versus-leukemia effect is essential. Genomic typing of HLA-A, -B, -C, -DRB1, and -DQB1 was retrospectively performed in 1298 donor-patient pairs in cases where marrow was donated from serologically HLA-A, -B, and -DR compatible donors. Single disparities of the HLA-A, -B, -C, or -DRB1 allele were independent risk factors for acute GVHD, and the synergistic effect of the HLA-C allele, mismatch with other HLA allele mismatches on acute GVHD was remarkable. HLA-A and/or HLA-B allele mismatch was found to be a significant factor for the occurrence of chronic GVHD. HLA class I (A, B, and/or C) allele mismatch caused a significantly higher incidence of engraftment failure than HLA match. Significant association of HLA-C allele mismatch with leukemia relapse was not observed. As the result of these events, HLA-A and/or HLA-B allele mismatch reduced overall survival remarkably in both standard-risk and high-risk leukemia cases, whereas the HLA-C mismatch or HILA-class 11 (DRB1 and/or DQB1) mismatch did not. Furthermore, multiple mismatch of the HLA locus was found to reduce survival in leukemia cases, Thus, the role of the HLA class I allele In unrelated bone marrow transplantation was elucidated. Notably, HLA-C alleles had a different mode from HLA-A or -B alleles for acute GVHD and survival. (C) 2002 by The American Society of Hematology.