次要组织相容性抗原（mHA）在异基因造血干细胞移植（alloHCT）后介导移植物抗白血病效应和移植物抗宿主病（GvHD）的作用得到了承认但尚未充分表征。本研究通过在两个大型患者队列中实现改进的mHA预测方法，旨在全面探讨mHA在alloHCT中的作用，即分析预测mHA的数量或个别mHA是否与临床结果相关。研究人群包括2249对由于急性髓性白血病和骨髓增生异常综合征接受alloHCT治疗的供受体。Cox比例风险模型显示，具有高于样本中数的I类mHA计数的患者具有较高的GvHD死亡危险性（风险比[HR] = 1.39，95％置信区间[CI] = 1.01，1.77，p = 0.046）。竞争风险分析确定类I mHA DLRCKYISL（GSTP）、WEHGPTSLL（CRISPLD2）和STSPTTNVL （SERPINF2）与增加的GVHD死亡（HR = 2.84，95％CI = 1.52，5.31，p = 0.01）、减少的白血病无病生存（LFS）（HR = 1.94，95％CI = 1.27，2.95，p = 0.044）和增加的与疾病相关的死亡（DRM）（HR = 2.32，95％CI = 1.5，3.6，p = 0.008）相关。一个II类mHA YQEIAAIPSAGRERQ（TACC2）与治疗相关死亡（TRM）风险增加相关（HR = 3.05，95％CI = 1.75，5.31，p = 0.02）。WEHGPTSLL和STSPTTNVL都存在于HLA单倍型B*40:01-C*03:04中，并显示出与增加的全因素死亡和DRM和降低的LFS呈正相关的剂量反应关系，表明这两个mHA以加性方式增加了死亡的风险。我们的研究报告了预测mHA多肽与alloHCT后临床结果相关性的首个大规模调查。© 2023 The Authors. 由Wiley Periodicals LLC出版的American Journal of Hematology。

The role of minor histocompatibility antigens (mHAs) in mediating graft versus leukemia and graft versus host disease (GvHD) following allogeneic hematopoietic cell transplantation (alloHCT) is recognized but not well-characterized. By implementing improved methods for mHA prediction in two large patient cohorts, this study aimed to comprehensively explore the role of mHAs in alloHCT by analyzing whether (1) the number of predicted mHAs, or (2) individual mHAs are associated with clinical outcomes. The study population consisted of 2249 donor-recipient pairs treated for acute myeloid leukemia and myelodysplastic syndrome with alloHCT. A Cox proportional hazard model showed that patients with a class I mHA count greater than the population median had an increased hazard of GvHD mortality (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.01, 1.77, p = .046). Competing risk analyses identified the class I mHAs DLRCKYISL (GSTP), WEHGPTSLL (CRISPLD2), and STSPTTNVL (SERPINF2) were associated with increased GVHD mortality (HR = 2.84, 95% CI = 1.52, 5.31, p = .01), decreased leukemia-free survival (LFS) (HR = 1.94, 95% CI = 1.27, 2.95, p = .044), and increased disease-related mortality (DRM) (HR = 2.32, 95% CI = 1.5, 3.6, p = .008), respectively. One class II mHA YQEIAAIPSAGRERQ (TACC2) was associated with increased risk of treatment-related mortality (TRM) (HR = 3.05, 95% CI = 1.75, 5.31, p = .02). WEHGPTSLL and STSPTTNVL were both present within HLA haplotype B*40:01-C*03:04 and showed a positive dose-response relationship with increased all-cause mortality and DRM and decreased LFS, indicating these two mHAs contribute to the risk of mortality in an additive manner. Our study reports the first large-scale investigation of the associations of predicted mHA peptides with clinical outcomes following alloHCT.© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.