Diverging effects of HLA-DPB1 matching status on outcome following unrelated donor transplantation depending on disease stage and the degree of matching for other HLA alleles
Diverging effects of HLA-DPB1 matching status on outcome following unrelated donor transplantation depending on disease stage and the degree of matching for other HLA alleles
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DOI：
10.1038/leu.2009.239
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发表时间：
2010-01-01
期刊：
影响因子：
11.4
通讯作者：
Madrigal, J. A.
中科院分区：
文献类型：
--
作者：
Shaw, B. E.;Mayor, N. P.;Madrigal, J. A.
疾病分期和受体/供体人类白细胞抗原（HLA）匹配是无亲属自愿供体（VUD）移植结果的重要决定因素。HLA-A, -B, -C, -DRB1， -DQB1的匹配是有益的，而DPB1匹配的重要性则更具争议。HLA匹配状态的影响可能因疾病分期而异。我们根据6个基因座的HLA匹配程度对488例白血病患者进行了研究，这些患者主要接受了t细胞耗尽的骨髓VUD移植。在早期白血病患者中，12/12匹配移植的生存率显著提高（5年：63年，10/10匹配的41%，P = 0.006），但没有晚期疾病。相反，在hla错配组（p9/10）中，DPB1错配组存在显著的生存优势（5年：39 vs DPB1匹配组21%，P = 0.008），特别是在晚期白血病（P = 0.01），在多变量分析中持续存在（优势比0.478；95%置信区间0.30,0.75;P = 0.001）。这些新发现表明，对于早期白血病患者来说，10/10匹配供体的最佳结果是通过匹配DPB1来实现的。相反，我们的结果表明，在接受hla不匹配移植的患者中，如果他们也不匹配DPB1，结果会明显更好。我们建议在独立的数据集中验证这些结果。白血病（2010）24,58-65；doi: 10.1038 / leu.2009.239;2009年11月19日在线发布
Disease stage and recipient/donor human leukocyte antigen (HLA) matching are important determinants of outcome in transplantation using volunteer-unrelated donors (VUD). Matching for HLA-A, -B, -C, -DRB1, -DQB1 is beneficial, whereas the importance of DPB1 matching is more controversial. The impact of HLA matching status may differ dependent on disease stage. We investigated the outcome according to the degree of HLA matching at 6 loci, in 488 recipients of predominantly T-cell depleted bone marrow VUD transplants for leukaemia. Survival was significantly better in 12/12-matched transplants in those with early leukaemia (5 years: 63 versus 41% in 10/10 matched, P = 0.006), but not late stage disease. Conversely, within the HLA-mismatched group (p9/10), there was a significant survival advantage to DPB1 mismatching (5 years: 39 versus 21% in DPB1 matched, P = 0.008), particularly in late leukaemia (P = 0.01), persisting in multivariate analysis (odds ratio 0.478; 95% confidence interval 0.30, 0.75; P = 0.001). These novel findings suggest that the best outcome for patients with early leukaemia, with a 10/10-matched donor, is achieved by matching for DPB1. Conversely, our results suggest that in patients receiving an HLA-mismatched graft, the outcome is significantly better if they are also mismatched for DPB1. We recommend validation of these results in independent datasets. Leukemia (2010) 24, 58-65; doi:10.1038/leu.2009.239; published online 19 November 2009