Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis.
Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis.
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在HLA A，B，C和DRB1匹配的供体 - 辅助HLA对白血病和骨髓增生综合征的脐带血液移植后结果的影响：回顾性分析。
DOI：
10.1016/s1470-2045(11)70260-1
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发表时间：
2011-12
期刊：
影响因子：
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通讯作者：
Center for International Blood and Marrow Transplant Research
中科院分区：
文献类型：
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作者：
Eapen M;Klein JP;Sanz GF;Spellman S;Ruggeri A;Anasetti C;Brown M;Champlin RE;Garcia-Lopez J;Hattersely G;Koegler G;Laughlin MJ;Michel G;Nabhan SK;Smith FO;Horowitz MM;Gluckman E;Rocha V;Eurocord-European Group for Blood and Marrow Transplantation;Netcord;Center for International Blood and Marrow Transplant Research
在人类白细胞抗原（HLA）C位点匹配的重要性还没有很好地定义无关的脐带血移植。脐带血单位的选择算法通常考虑A和B的中等分辨率HLA分型，以及DRB 1的等位基因水平。我们的目的是确定除了当前的选择标准之外，HLA-C匹配的相对重要性。我们采用考克斯回归分析方法回顾性研究了供受者HLA配型对803例单次脐带血移植治疗白血病（N=727）和骨髓增生异常综合征（N=76）的结局的影响。主要终点是移植相关死亡率。使用分子技术进行HLA分型，HLA-A、-B和-C的最小中间分辨率和DRB 1的等位基因水平。与HLA-A、-B、-C、-DRB 1匹配的移植相比（N=69; HR 1.00），HLA-A、-B、-DRB 1匹配和HLA-C不匹配的移植后移植相关死亡风险更高（N=23;HR 3.97，95%CI 1.27 - 12.40，p=0.018）。与HLA-C匹配且HLA-A、-B或-DRB 1单次错配的移植相比，HLA-A或-B或-DRB 1单次错配且HLA-C错配的移植后移植相关的死亡风险也更高（N=234; HR 1.70 95%CI 1.06 - 2.74，p=0.029）A、-B或-DRB 1（N=127; HR 1.00）。检查HLA不一致对移植相关死亡率的总体影响，两个单位不匹配的风险更高，（N=259; HR 3.27 95% CI 1.42 - 7.54，p=0.006），3例（N=253; HR 3.34 95% CI 1.45 - 7.71，p=0.005）或4个（N=75; HR 3.51 95% CI 1.44 - 8.58，p=0.006）位点。这些数据表明，我们重新评估了目前的策略，脐带血单位的选择，考虑匹配的单位在HLA-A，-B，-DRB 1或在HLA-A，-B或DRB 1存在一个单一的基因座错配HLA-C，以尽量减少死亡风险。国家癌症研究所、国家心肺和血液研究所和国家过敏和传染病研究所;白血病和淋巴瘤协会临床研究奖学者;卫生资源和服务管理局;美国海军部海军研究办公室;儿童白血病研究协会;卫生部医学研究所赠款TGIR。
The importance of matching at the human leukocyte antigen (HLA) C locus has not been well defined for unrelated umbilical cord blood transplantation. The selection algorithm for umbilical cord blood units generally considers intermediate resolution HLA typing at A and B, and allele-level at DRB1. We aimed to determine the relative importance of matching at HLA-C in addition to current selection criteria. We used Cox regression to retrospectively examine for the effect of donor-recipient HLA matching on outcomes of 803 single umbilical cord blood transplantations for leukemia (N=727) and myelodysplastic syndrome (N=76). The primary endpoint was transplant-related mortality. HLA typing was performed using molecular techniques with a minimum of intermediate resolution for HLA-A, -B and -C and allele-level for DRB1. Compared to transplantations matched at HLA-A, -B, -C, -DRB1 (N=69; HR 1.00), transplant-related mortality risks were higher after transplantations matched at HLA-A, -B, -DRB1 and mismatched at HLA-C (N=23;HR 3.97, 95% CI 1.27 – 12.40, p=0.018). Transplant-related mortality risk were also higher after transplantations with a single mismatch at HLA-A or -B, or -DRB1 and mismatched at HLA-C (N=234; HR 1.70 95% CI 1.06 – 2.74, p=0.029) compared to transplantations matched at HLA-C with a single mismatch at HLA-A, -B, or -DRB1 (N=127; HR 1.00). Examining for an overall effect of HLA disparity on transplant-related mortality, risks were higher with units mismatched at two (N=259; HR 3.27 95% CI 1.42 – 7.54, p=0.006), three (N=253; HR 3.34 95% CI 1.45 – 7.71, p=0.005) or four (N=75; HR 3.51 95% CI 1.44 – 8.58, p=0.006) loci compared to matched units (N=69; HR 1.00). These data suggest that we re-evaluate the current strategy for umbilical cord blood unit selection, by considering matching at HLA-C for units that are matched at HLA-A, -B, -DRB1 or in the presence of a single locus mismatch at HLA-A, -B or DRB1 to minimize mortality risks. National Cancer Institute, National Heart Lung and Blood Institute and National Institute for Allergy and Infectious Diseases; Scholar in Clinical Research Award, the Leukemia and Lymphoma Society; Heath Resources and Services Administration; Office of Naval Research, United States Department of Navy; Children’s Leukemia Research Association; INSERM grant TGIR.