Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation
Nonpermissive HLA-DPB1 disparity is a significant independent risk factor for mortality after unrelated hematopoietic stem cell transplantation
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DOI：
10.1182/blood-2009-01-200378
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发表时间：
2009-08-13
期刊：
影响因子：
20.3
通讯作者：
Benedetti, F.
中科院分区：
文献类型：
--
作者：
Crocchiolo, Roberto;Zino, Elisabetta;Benedetti, F.
供体-受体人类白细胞抗原 (HLA)-DPB1 匹配对于无关造血干细胞移植 (HSCT) 临床结果的重要性存在争议。我们之前描述了一种基于 T 细胞同种异体反应模式的非许可 HLA-DPB1 差异算法，涉及 HLA-DPB1*0901、*1001、*1701、*0301、*1401、*4501。通过重新审视 HLA-DPB1*02 的免疫原性，开发了一种改进的算法，并在意大利肿瘤血液学成年患者登记处促进的 621 例无关 HSCT 中进行了回顾性测试。事实证明，修改后的算法比原始算法更能预测结果，与非许可移植相比，许可移植的 2 年生存 KaplanMeier 概率显着更高（55% vs 39%，P = .005）。这是非复发死亡风险增加的结果（风险比 [HR] = 1.74；置信区间 [CI]，1.19-2.53；P = .004），但不是复发风险增加（HR = 1.02；CI，0.73-1.42；P = .92）。在 10 例等位基因匹配移植中的 10 例（HR = 2.12；CI，1.23-3.64；P = .006）和 10 例等位基因匹配移植中的 9 例（HR = 2.21；CI，1.28-3.80；P = .004）中，无论是在早期阶段还是在晚期阶段，由于不允许的 HLA-DPB1 差异导致的总体死亡率风险的增加是相似的。疾病晚期。这些数据要求重新审视当前针对不相关 HSCT 的 HLA 匹配策略，表明搜索应直接针对 HLA-DPB1 允许的、10 中的 10 或 10 中的 9 匹配供体的识别。 （血。2009；114：1437-1444）
The importance of donor-recipient human leukocyte antigen (HLA)-DPB1 matching for the clinical outcome of unrelated hematopoietic stem cell transplantation (HSCT) is controversial. We have previously described an algorithm for nonpermissive HLA-DPB1 disparities involving HLA-DPB1*0901,*1001,*1701,*0301,*1401,*4501, based on T-cell alloreactivity patterns. By revisiting the immunogenicity of HLA-DPB1*02, a modified algorithm was developed and retrospectively tested in 621 unrelated HSCTs facilitated through the Italian Registry for onco-hematologic adult patients. The modified algorithm proved to be markedly more predictive of outcome than the original one, with significantly higher KaplanMeier probabilities of 2-year survival in permissive compared with nonpermissive transplantations (55% vs 39%, P = .005). This was the result of increased adjusted hazards of nonrelapse mortality (hazard ratio [HR] = 1.74; confidence interval [CI], 1.19-2.53; P = .004) but not of relapse (HR = 1.02; CI, 0.73-1.42; P = .92). The increase in the hazards of overall mortality by nonpermissive HLA-DPB1 disparity was similar in 10 of 10 (HR = 2.12; CI, 1.23-3.64; P = .006) and 9 of 10 allele-matched transplantations (HR = 2.21; CI, 1.28-3.80; P = .004), both in early-stage and in advanced-stage disease. These data call for revisiting current HLA matching strategies for unrelated HSCT, suggesting that searches should be directed up-front toward identification of HLA-DPB1 permissive, 10 of 10 or 9 of 10 matched donors. (Blood. 2009; 114:1437-1444)