人类白细胞抗原（HLA）不匹配会降低造血细胞移植（HCT）后血癌患者的生存率。 HCT 实践的最新进展，特别是移植后环磷酰胺 (PTCy) 预防移植物抗宿主病 (GVHD) 如何影响 HLA 风险关联尚不清楚。该研究包括 17,292 例具有 6 位点高分辨率 HLA 分型的不相关 HCT 2016年至2020年间，主要针对急性白血病或相关髓系肿瘤进行了1,523例移植手术，其中包括1,523例PTCy移植。通过多变量 Cox 回归模型评估 HLA 风险关联，以总生存 (OS) 作为主要终点。与完全匹配的移植相比，HLA 不匹配的 OS 较低（风险比 [HR]，1.23 [99% CI，1.14 至 1.33] ; P < .001)。这是由 I 类 HLA-A、HLA-B、HLA-C 驱动的（HR，1.29 [99% CI，1.19 至 1.41]；P < .001），但不是由 II 类 HLA-DRB1 和 HLA-DQB1 驱动（HR， 1.07 [99% CI，0.93 至 1.23]；P = .19）。 I 类抗原水平错配与等位基因水平错配相比，与较差的 OS 相关（HR，1.36 [99% CI，1.24 至 1.49]；P < .001），I 类移植物抗宿主肽结合基序也是如此（ PBM) 错配与匹配相比 (HR, 1.42 [99% CI, 1.28 至 1.59]; P < .001)。与 HLA 匹配移植中的常规预防相比，使用 PTCy 改善了 GVHD、无复发生存率（HR，0.77 [0.66 至 0.9]；P < .001）。 HLA 不匹配增加了 PTCy 移植的死亡率（HR，1.32 [1.04 至 1.68]；P = .003），与非 PTCy 移植相似（交互作用 P = .43）。I 类 HLA 不匹配，但不是 II 类不匹配，尤其是在抗原上和 PBM 水平，与当代不相关的 HCT 中的较差生存率相关。与 PTCy 移植相比，非 PTCy 移植的这些效果没有显着差异。现代 HCT 中仍应考虑优化 HLA 匹配。

Human leukocyte antigen (HLA) mismatching can reduce survival of patients with blood cancer after hematopoietic cell transplantation (HCT). How recent advances in HCT practice, in particular graft-versus-host disease (GVHD) prophylaxis by post-transplantation cyclophosphamide (PTCy), influence HLA risk associations is unknown.The study included 17,292 unrelated HCTs with 6-locus high-resolution HLA typing, performed mainly for acute leukemia or related myeloid neoplasms between 2016 and 2020, including 1,523 transplants with PTCy. HLA risk associations were evaluated by multivariable Cox regression models, with overall survival (OS) as primary end point.OS was lower in HLA mismatched compared with fully matched transplants (hazard ratio [HR], 1.23 [99% CI, 1.14 to 1.33]; P < .001). This was driven by class I HLA-A, HLA-B, HLA-C (HR, 1.29 [99% CI, 1.19 to 1.41]; P < .001) but not class II HLA-DRB1 and HLA-DQB1 (HR, 1.07 [99% CI, 0.93 to 1.23]; P = .19). Class I antigen-level mismatches were associated with worse OS than allele-level mismatches (HR, 1.36 [99% CI, 1.24 to 1.49]; P < .001), as were class I graft-versus-host peptide-binding motif (PBM) mismatches compared with matches (HR, 1.42 [99% CI, 1.28 to 1.59]; P < .001). The use of PTCy improved GVHD, relapse-free survival compared with conventional prophylaxis in HLA-matched transplants (HR, 0.77 [0.66 to 0.9]; P < .001). HLA mismatching increased mortality in PTCy transplants (HR, 1.32 [1.04 to 1.68]; P = .003) similarly as in non-PTCy transplants (interaction P = .43).Class I but not class II HLA mismatches, especially at the antigen and PBM level, are associated with inferior survival in contemporary unrelated HCT. These effects are not significantly different between non-PTCy compared with PTCy transplants. Optimized HLA matching should still be considered in modern HCT.