High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation
High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation
复制标题
DOI：
10.1182/blood-2007-06-097386
复制
发表时间：
2007-12-15
期刊：
影响因子：
20.3
通讯作者：
Anasetti, Claudio
中科院分区：
文献类型：
--
作者：
Lee, Stephanie J.;Klein, John;Anasetti, Claudio
各种人类白细胞抗原（HLA）基因座的相对重要性和它们匹配的分辨率水平尚未完全确定无关供体移植。为了解决这个问题，我们分析了1988年至2003年在美国进行的3857例移植的国家骨髓捐献者计划数据。对患者-供体对进行HLA-A、-B、-C、-DRB 1、-DQB 1、-DQA 1、-DPB 1和-DPA 1等位基因的完全分型。HLA-A、-B、-C和-DRB 1的高分辨率DNA匹配（8/8匹配）是与最高存活率相关的最低匹配水平。在HLA-A、-B、-C或-DRB 1上通过低分辨率或高分辨率DNA检测发现的单一错配（7/8匹配）与较高的死亡率（相对风险，1.25; 95%CI，1.13-1.38; P <0.001）和43%的1年生存率相关，而8/8匹配对的1年生存率为52%。HLA-B或HLA-C的单一错配似乎比HLA-A或HLA-DRB 1的错配更好地耐受。两个或两个以上位点的错配增加了风险。HLA-DP或-DQ位点的错配和HLA类型以外的供体因素与生存率无关。在多变量模型中，患者年龄、种族、疾病分期和巨细胞病毒状态与供者HLA配型一样预测生存。HLA-A、-B、-C和-DRB 1等位基因的高分辨率DNA匹配与较高的存活率相关。
The relative importance of various human leukocyte antigen (HLA) loci and the resolution level at which they are matched has not been fully defined for unrelated donor transplantation. To address this question, National Marrow Donor Program data from 3857 transplantations performed from 1988 to 2003 in the United States were analyzed. Patient-donor pairs were fully typed for HLA-A, -B, -C, -DRB1, -DQB1, -DQA1, -DPB1, and -DPA1 alleles. High-resolution DNA matching for HLA-A, -B, -C, and -DRB1 (8/8 match) was the minimum level of matching associated with the highest survival. A single mismatch detected by low- or high-resolution DNA testing at HLA-A, -B, -C or -DRB1 (7/8 match) was associated with higher mortality (relative risk, 1.25; 95% Cl, 1.13-1.38; P < .001) and 1-year survival of 43% compared with 52% for 8/8 matched pairs. Single mismatches at HLA-B or HLA-C appear better tolerated than mismatches at HLA-A or HLA-DRB1. Mismatching at 2 or more loci compounded the risk. Mismatching at HLA-DP or -DQ loci and donor factors other than HLA type were not associated with survival. In multivariate modeling, patient age, race, disease stage, and cytomegalovirus status were as predictive of survival as donor HLA matching. High-resolution DNA matching for HLA-A, -B, -C, and -DRB1 alleles is associated with higher rates of survival.