甲氨蝶呤（MTX）在同种异体造血干细胞移植（allo-HSCT）中作为预防移植物抗宿主病（GvHD）的药物已被证明能有效降低移植物与次植入综合征（Peri-ES）和急性GvHD（aGvHD）的发生率。MTX的药代动力学变化与编码药物代谢酶和转运蛋白基因的基因多态性密切相关。然而，当前的研究主要集中在白血病或自身免疫性疾病上，关于同种异体造血干细胞移植的研究报道有限。在这里，我们回顾性评估了在单个中心接受恶性肿瘤单倍型HSCT（haplo-HSCT）的57名儿科患者中，MTX相关转运蛋白和代谢酶基因多态性、临床特征和预后之间的关系。 我们发现在我们的队列中所有基因多态性都符合Hardy-Weinberg平衡。我们发现血小板恢复时间与ABCB1（1236C>T）之间存在显著相关性（p=0.042）。与SLCO1B1（1865+4846T>C）TT患者相比，SLCO1B1（1865+4846T>C）TC/CC患者的Peri-ES发病率增加（p=0.030）。根据多元Cox分析，我们发现SLCO1B1（1865+4846T>C）TT基因型是Peri-ES发病的独立保护因子（风险比（HR）=0.464，p=0.031），重新输注的单个核细胞剂量与II-IV级aGvHD显著相关（HR=2.604，p=0.039）。 总之，我们的研究结果证明宿主基因型可能调节Peri-ES的发病风险，有助于更好地理解个体差异的疗效，并促进个体化GvHD预防策略的发展。 版权所有 © 2023 Ji, Zhang, Hu, Liu, Cao, Gao, Li, Tian, Kong, Wu, Ling, Xiao, Lu, Li, Yao, Qin和Hu。

Methotrexate (MTX), utilized as a graft-versus-host disease (GvHD) prophylactic agent in allogeneic hematopoietic stem cell transplantation (allo-HSCT), has been proven to effectively decrease the occurrence of the peri-engraftment syndrome (Peri-ES) and acute GvHD (aGvHD). Changes in the pharmacodynamics of MTX are closely associated with gene polymorphisms in genes encoding drug-metabolizing enzymes and transporters. Nevertheless, the current studies mainly concentrate on leukemia or autoimmune diseases, and limited studies on allo-HSCT were reported.Here, we retrospectively assessed the relationship between MTX-related transporter and metabolizing enzyme gene polymorphisms, clinical characteristics, and outcomes in 57 pediatric patients who received haploid HSCT (haplo-HSCT) with malignant tumors at a single center.We discovered all gene polymorphisms were in the Hardy-Weinberg equilibrium in our cohort. We discovered a significant correlation between platelet recovery time and ABCB1 (1236C>T) (p = 0.042). Compared with patients with SLCO1B1 (1865+4846T>C) TT, patients with SLCO1B1 (1865+4846T>C) TC/CC had an increased incidence of Peri-ES (p = 0.030). Based on the multivariate Cox analysis, we discovered that SLCO1B1 (1865+4846T>C) TT genotype was an independent protective factor for Peri-ES morbidity (hazard ratio (HR) = 0.464, p = 0.031), and the dose of mononuclear cells reinfused was significantly correlated with II-IV aGvHD (HR = 2.604, p = 0.039).In summary, our findings prove that the host's genotypes might modify the risk of developing Peri-ES, contribute to a better understanding of the inter-individual difference in efficacy, and facilitate the development of individualized approaches to GvHD prophylaxis.Copyright © 2023 Ji, Zhang, Hu, Liu, Cao, Gao, Li, Tian, Kong, Wu, Ling, Xiao, Lu, Li, Yao, Qin and Hu.