Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Eur J Haematol. 2017 Sep;99(3):275-282. doi: 10.1111/ejh.12916. Epub 2017 Jul 21.
HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution.
Retrospective HLA-DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 loci (10/10). Using the ImMunoGeneTics/HLA T-cell epitope matching algorithm, mismatch status was classified as permissive or non-permissive.
Of 153 donor-recipient pairs, 22 (14.4%) were HLA-DPB1 matches, 64 (42.8%) permissive mismatches, and 67 (43.8%) non-permissive mismatches. DPB1 mismatch increased risk of chronic graft-versus-host disease (cGVHD; RR 2.89 [1.19-9.53], P=.016) compared with DPB1-matched transplants, but there were no differences in overall mortality, risk of relapse, or acute GVHD (aGVHD). Combining matches and permissive mismatches and comparing to non-permissive mismatches, there was no significant difference in overall survival or relapse; however, patients receiving non-permissive mismatched transplants experienced greater risk of aGVHD overall and severe aGVHD (RR 1.66 [1.13-2.44], P=.010 and RR 1.97 [1.10-3.59], P=.024, respectively).
In this single-center study, HLA-DPB1 matching influenced outcomes of patients undergoing ASCT for hematologic malignancy.
HLA-DPB1 匹配可能影响异基因造血干细胞移植(ASCT)的结果;然而,该基因座与 HLA 基因的其余部分没有连锁不平衡。根据 T 细胞表位对 HLA-DPB1 错配进行分类后,避免非许可性错配可能会影响生存。我们在一个学术机构中检验了这一假设。
对 153 名接受 ASCT 和无关供体 HLA-A、B、C、DRB1 和 DQB1 位点(10/10)匹配的成年患者进行回顾性 HLA-DPB1 基因分型。使用 ImmunoGeneTics/HLA T 细胞表位匹配算法,错配状态被分类为许可性或非许可性。
在 153 对供受者中,22 对(14.4%)为 HLA-DPB1 匹配,64 对(42.8%)为许可性错配,67 对(43.8%)为非许可性错配。与 HLA-DPB1 匹配的移植相比,DPB1 错配增加了慢性移植物抗宿主病(cGVHD;RR 2.89 [1.19-9.53],P=.016)的风险,但在总死亡率、复发风险或急性移植物抗宿主病(aGVHD)方面没有差异。将匹配和许可性错配与非许可性错配相结合,并与非许可性错配进行比较,总生存或复发无显著差异;然而,接受非许可性错配移植的患者总体上发生 aGVHD 和严重 aGVHD 的风险更高(RR 1.66 [1.13-2.44],P=.010 和 RR 1.97 [1.10-3.59],P=.024)。
在这项单中心研究中,HLA-DPB1 匹配影响了接受血液恶性肿瘤 ASCT 的患者的结果。