Human leukocyte antigen (HLA) haplotype matching in unrelated single HLA allele mismatch bone marrow transplantation
Human leukocyte antigen (HLA) haplotype matching in unrelated single HLA allele mismatch bone marrow transplantation
复制标题
无关单 HLA 等位基因错配骨髓移植中的人类白细胞抗原 (HLA) 单倍型匹配
DOI：
10.1038/s41409-021-01552-y
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发表时间：
2022
影响因子：
4.8
通讯作者：
HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation
中科院分区：
文献类型：
--
作者：
Kawajiri Akihisa;Kawase Takakazu;Tanaka Hidenori et al.;HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation
匹配人类白细胞抗原(HLA)单倍型在非亲缘异基因骨髓移植(allo-BMT)中的作用尚不清楚。在这里，我们用数学方法推算了3657例接受了不相关的单个HLA等位基因不匹配的allo-BMT的患者的HLA单倍型，这些患者来自日本的造血移植登记程序--移植登记统一管理计划(Trump)数据库。我们成功地推测了1365例(37.3%)患者和供者的人类白细胞抗原单倍型，≥概率为90%。单倍型匹配组1326例(97.1%)，非单倍型匹配组39例(2.9%)。在非单倍型匹配的组中，无病生存率明显较差。多变量分析显示，非单倍型匹配是降低无病生存率的独立危险因素(风险比，1.5 4[95%可信区间：1.0 1-2.36]；p= 0.047)。然而，两组之间的总体存活率没有显著差异。3-IV级急性和慢性移植物抗宿主病的发生率在两组之间没有显著差异。此外，两组之间复发和非复发死亡率的累积发生率没有显著差异。我们的发现表明，使用数学方法计算单倍型有助于避免将单倍型不匹配的捐赠者移植到患者身上，从而改善allo-BMT的结果。
The role of matching human leukocyte antigen (HLA) haplotypes in unrelated allogeneic bone marrow transplantation (allo-BMT) remains unclear. Here, we imputed the HLA haplotypes of 3657 patients who received unrelated single HLA allele-mismatched allo-BMT, included from the Transplant Registry Unified Management Program (TRUMP) database, the Japanese registry program for hematopoietic transplantation, using mathematical methods. We successfully imputed the HLA haplotypes of both patients and donors in 1365 cases (37.3%) with ≥90% probability. Of the patients, 1326 (97.1%) and 39 (2.9%) were categorized into one-haplotype-matched and no-haplotype-matched groups, respectively. Disease-free survival was significantly worse in the no-haplotype-matched group. Multivariate analyses revealed that no-haplotype-match was an independent risk factor for reducing disease-free survival (hazard ratio, 1.54 [95% confidence interval: 1.01–2.36];p= 0.047). However, the overall survival did not significantly differ between the groups. The incidence of grade III–IV acute and chronic graft-versus-host disease did not significantly differ between the groups. Furthermore, there were no significant differences in the cumulative incidences of relapse and non-relapse mortality between the groups. Our findings suggest that imputing haplotypes using a mathematical approach can help to avoid transplanting patients with donors who do not share matching haplotypes, thereby improving the outcome of allo-BMT.