Hematopoietic cell transplantation from HLA-haploidentical related donors is increasingly used to treat hematologic cancers; however, characteristics of the optimal haploidentical donor have not been established. We studied the role of donor HLA mismatching in graft-versus-host disease (GVHD), disease recurrence, and survival after haploidentical donor transplantation with posttransplantation cyclophosphamide (PTCy) for 1434 acute leukemia or myelodysplastic syndrome patients reported to the Center for International Blood and Marrow Transplant Research. The impact of mismatching in the graft-versus-host vector for HLA-A, -B, -C, -DRB1, and -DQB1 alleles, the HLA-B leader, and HLA-DPB1 T-cell epitope (TCE) were studied using multivariable regression methods. Outcome was associated with HLA (mis)matches at individual loci rather than the total number of HLA mismatches. HLA-DRB1 mismatches were associated with lower risk of disease recurrence. HLA-DRB1 mismatching with HLA-DQB1 matching correlated with improved disease-free survival. HLA-B leader matching and HLA-DPB1 TCE-nonpermissive mismatching were each associated with improved overall survival. HLA-C matching lowered chronic GVHD risk, and the level of HLA-C expression correlated with transplant-related mortality. Matching status at the HLA-B leader and HLA-DRB1, -DQB1, and -DPB1 predicted disease-free survival, as did patient and donor cytomegalovirus serostatus, patient age, and comorbidity index. A web-based tool was developed to facilitate selection of the best haploidentical-related donor by calculating disease-free survival based on these characteristics. In conclusion, HLA factors influence the success of haploidentical transplantation with PTCy. HLA-DRB1 and -DPB1 mismatching and HLA-C, -B leader, and -DQB1 matching are favorable. Consideration of HLA factors may help to optimize the selection of haploidentical related donors.

中文翻译：

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HLA 可以为移植后环磷酰胺进行半相合干细胞移植后的风险预测提供信息。

来自HLA半相合相关供体的造血细胞移植越来越多地用于治疗血液癌症；然而，最佳单倍体供体的特征尚未确定。我们研究了向国际血液和骨髓移植中心报告的 1434 名急性白血病或骨髓增生异常综合征患者，在使用移植后环磷酰胺 (PTCy) 进行半相合供体移植后，供体 HLA 不匹配在移植物抗宿主病 (GVHD)、疾病复发和生存中的作用。骨髓移植研究。研究了移植物抗宿主载体错配对 HLA-A、-B、-C、-DRB1 和 -DQB1 等位基因、HLA-B 前导序列和 HLA-DPB1 T 细胞表位 (TCE) 的影响使用多变量回归方法。结果与各个位点的 HLA（错）匹配相关，而不是与 HLA 错配总数相关。HLA-DRB1 错配与较低的疾病复发风险相关。HLA-DRB1 不匹配与 HLA-DQB1 匹配与无病生存率改善相关。HLA-B 先导序列匹配和 HLA-DPB1 TCE 不允许的错配均与总体生存率的提高相关。HLA-C 匹配可降低慢性 GVHD 风险，并且 HLA-C 表达水平与移植相关死亡率相关。HLA-B 前导序列与 HLA-DRB1、-DQB1 和 -DPB1 的匹配状态可预测无病生存期，患者和供体巨细胞病毒血清状态、患者年龄和合并症指数也可预测无病生存期。开发了一种基于网络的工具，通过根据这些特征计算无病生存率来促进选择最佳的单倍体相关供体。总之，HLA 因素影响 PTCy 半相合移植的成功。HLA-DRB1 和-DPB1 不匹配以及HLA-C、-B 前导序列和-DQB1 匹配是有利的。考虑 HLA 因素可能有助于优化半相合相关供体的选择。