The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
University of Colorado Blood Bank and Clinimmune Laboratory, Aurora, CO, USA.
Bone Marrow Transplant. 2024 Oct;59(10):1433-1439. doi: 10.1038/s41409-024-02341-z. Epub 2024 Jul 31.
Graft versus tumor relies on tumor-associated antigens (TAAs) that are presented to donor T cells via human leukocyte antigens (HLAs). The HLA evolutionary divergence (HED) between alleles of a single individual can dictate the ability to present TAAs. The impact of HED in haploidentical donor transplantation (HIDT) has not been studied. We studied the effect of HED on transplant outcomes following HIDT. We analyzed 322 consecutive recipient/donor pairs with a median follow-up of 57.2 months. Pairwise divergence of HLA class I and II showed that HLA-B, -DRB1, and -DQB1 contributing most to mean HED. The mean HED was class I 6.85 (HLA-A 7.08, -B 8.24, and -C 5.07), class II 8.58 (HLA-DRB1 10.97, -DQB1 10.06 and -DPB1 4.06). A high HED in class I mismatched recipient/donor haplotype (RD MM) was significant for worse DFS (HR 1.11, p = 0.020), and relapse (HR 1.11, p = 0.02). Also, a high HED in RD MM HLA-B haplotype had worse OS (HR 1.07, p = 0.02), DFS (HR 1.09, p = 0.002), higher relapse (HR 1.10, p = 0.003), and similar NRM to low HED. The multivariate analysis showed that high HED in RD MM HLA-B (≥7.8 vs <7.8) had worse DFS (HR 1.53, p = 0.01), higher relapse (HR 1.61, p = 0.024), and similar NRM and OS.
移植物抗宿主病依赖于肿瘤相关抗原（TAA），这些抗原通过人类白细胞抗原（HLA）递呈给供体 T 细胞。个体中单个等位基因的 HLA 进化差异（HED）可以决定递呈 TAA 的能力。HED 在单倍体相合供者移植（HIDT）中的影响尚未得到研究。我们研究了 HED 对 HIDT 后移植结果的影响。我们分析了 322 对连续的受者/供者对，中位随访时间为 57.2 个月。HLA Ⅰ类和Ⅱ类的成对差异表明，HLA-B、-DRB1 和 -DQB1 对平均 HED 的贡献最大。平均 HED 为Ⅰ类 6.85（HLA-A 7.08、-B 8.24 和 -C 5.07），Ⅱ类 8.58（HLA-DRB1 10.97、-DQB1 10.06 和 -DPB1 4.06）。Ⅰ类错配受者/供者单倍型（RD MM）的高 HED 与较差的DFS（HR 1.11，p=0.020）和复发（HR 1.11，p=0.02）显著相关。此外，RD MM HLA-B 单倍型的高 HED 与较差的 OS（HR 1.07，p=0.02）、DFS（HR 1.09，p=0.002）、更高的复发（HR 1.10，p=0.003）和类似的非复发死亡率（NRM）相关，与低 HED 相比。多变量分析显示，RD MM HLA-B 中的高 HED（≥7.8 与<7.8）DFS 较差（HR 1.53，p=0.01），复发率较高（HR 1.61，p=0.024），NRM 和 OS 相似。
