Table_4_Impact of HLA Epitope Matching on Outcomes After Unrelated Bone Marrow Transplantation.xlsx

The significance of antibody-identified epitopes stimulating humoral alloimmunity is not well understood in the identification of non-permissive human leukocyte antigen (HLA) mismatching patterns in hematopoietic stem cell transplantation (HSCT). This was a retrospective study in a cohort of 9,991 patients who underwent their first HSCT for hematologic malignancies from unrelated bone marrow donors in the Transplant Registry Unified Management Program (TRUMP). HLA eplet mismatches (EMM) were quantified using HLAMatchmaker (HLAMM). The median age of patients was 48 years (range, 16 to 77). The number of EMM in recipient-donor pairs in our study population ranged from 0 to 37 in HLA class I (median, 0) and 0 to 60 in HLA class II (median, 1). In addition to the known high-risk mismatch patterns in the Japanese cohort, HLA-C EMM in the GVH direction was associated with a significantly higher risk for grade III-IV aGVHD, leading to a higher risk of non-relapse mortality and lower overall survival (compared with HLA-C matched patients, HR 1.67, 95% CI 1.44–1.95; HR 1.39, 95% CI 1.25–1.54; HR 1.20, 95% CI 1.10–1.30, respectively). HLAMM-based epitope matching might be useful for identifying patients who are at high risk for serious complications after HSCT from HLA mismatched unrelated donors.

在造血干细胞移植（hematopoietic stem cell transplantation, HSCT）中非容许性人类白细胞抗原（human leukocyte antigen, HLA）错配模式的识别中，抗体识别表位激发体液同种异体免疫的意义尚未得到充分阐释。本研究依托移植登记统一管理项目（Transplant Registry Unified Management Program, TRUMP），针对9991例首次接受无关骨髓供者造血干细胞移植治疗血液系统恶性肿瘤的患者队列开展回顾性研究。采用HLAMatchmaker（HLAMM）量化HLA表位错配（eplet mismatches, EMM）情况。本研究纳入患者的中位年龄为48岁（范围16~77岁）。研究人群中受体-供体对的HLA表位错配数在HLA I类中为0~37（中位值为0），HLA II类中为0~60（中位值为1）。除日本队列中已明确的高风险错配模式外，移植物抗宿主方向的HLA-C表位错配与Ⅲ-Ⅳ级急性移植物抗宿主病（acute graft-versus-host disease, aGVHD）的发生风险显著升高相关，进而导致更高的非复发死亡率及更差的总生存期（相较于HLA-C匹配患者，风险比（hazard ratio, HR）分别为1.67、95%置信区间（confidence interval, CI）1.44~1.95；1.39、95%CI 1.25~1.54；1.20、95%CI 1.10~1.30）。基于HLAMatchmaker的表位匹配策略或可用于识别HLA错配无关供者造血干细胞移植后发生严重并发症的高风险患者。