Ji Qi, Hu Yixin, Liu Minyuan, Liu Lixia, Zheng Jiajia, Du Zhizhuo, Gao Li, Xiao Peifang, Ling Jing, Fan Liyan, Bian Xinni, Lou Feng, Cao Shanbo, Li Jie, Tian Yuanyuan, Lu Jun, Qin Jiayue, Hu Shaoyan
Department of Hematology and Oncology, Children's Hospital of Soochow University, No. 92, Zhongnan Street, Suzhou, 215002, China.
Department of Medical Affairs, Acornmed Biotechnology Co., Ltd, Floor 18, Block 5, Yard 18, Kechuang 13 RD, Beijing, 100176, China.
BMC Cancer. 2024 Dec 18;24(1):1516. doi: 10.1186/s12885-024-13227-0.
Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) serves as an important option for patients without an HLA matched donor in treating hematological disorders, while patients may experience various complications after transplantation. Mycophenolate mofetil (MMF), a cornerstone drug for graft-versus-host disease (GvHD) prophylaxis, effectively reduces the incidence of acute GvHD, and the efficacy of MMF varies among individuals associated with MMF-related transporters and metabolic enzymes single nucleotide polymorphisms (SNPs). However, limited studies have systematically reported the correlations between the MMF-related SNPs and post-transplant complications.
Here, we conducted a retrospective study involving 90 pediatric patients with hematological disorders who underwent haplo-HSCT at a single center. All patients were subjected to MMF-related SNP testing, combined with common clinical characteristics, to be correlated with post-transplant complications.
We observed that all 15 MMF-related SNPs were in Hardy-Weinberg equilibrium. Based on multivariate Cox regression analysis of post-transplant complications, we discovered that SLCO1B1 (521T > C) variant genotype was an independent protective factor for chronic GvHD (HR = 0.25, 95% confidence interval (CI) (0.08-0.84)). For viral infection, CYP2C8 (1291 + 106T > C) variant genotype was an independent risk factor for cytomegalovirus infection (HR = 2.98, 95% CI (1.18-7.53)). As to hemorrhagic cystitis, SLCO1B1 (1865 + 4846T > C) variant genotype was an independent protective factor, while older age was considered as an independent risk factor (HR = 0.41, 95% CI (0.19-0.85); HR = 2.52, 95% CI (1.14-5.54), respectively). No statistical significance was discovered between common clinical characteristics and MMF-related SNPs with other complications, including grade II-IV/III-IV acute GvHD, Epstein-Barr virus infection, peri-engraftment syndrome, and capillary leak syndrome. We also discovered SLCO1B1 (597 C > T) and SLC29A1 (-162 + 228 A > C) variant genotypes are both independent factors for cumulative incidence of relapse after haplo-HSCT (HR = 4.02, 95% CI (1.42-11.44); HR = 0.18, 95% CI (0.07-0.43), respectively).
Our findings highlight the significance of MMF-related transporters and metabolic enzymes SNPs in the development of post-transplant complications, contributing to facilitating personalized risk assessment and improving the clinical management in haplo-HSCT patients.
单倍型相合造血干细胞移植（Haplo-HSCT）是治疗血液系统疾病且无HLA相匹配供者患者的重要选择，然而患者移植后可能会出现各种并发症。霉酚酸酯（MMF）是预防移植物抗宿主病（GvHD）的基石药物，可有效降低急性GvHD的发生率，且MMF的疗效因个体差异与MMF相关转运体和代谢酶单核苷酸多态性（SNP）有关。然而，有限的研究系统报道了MMF相关SNP与移植后并发症之间的相关性。
在此，我们进行了一项回顾性研究，纳入了90例在单一中心接受Haplo-HSCT的儿科血液系统疾病患者。所有患者均接受MMF相关SNP检测，并结合常见临床特征，以与移植后并发症进行相关性分析。
我们观察到所有15个MMF相关SNP均处于Hardy-Weinberg平衡。基于对移植后并发症的多因素Cox回归分析，我们发现SLCO1B1（521T＞C）变异基因型是慢性GvHD的独立保护因素（HR = 0.25，95%置信区间（CI）（0.08 - 0.84））。对于病毒感染，CYP2C8（1291 + 106T＞C）变异基因型是巨细胞病毒感染的独立危险因素（HR = 2.98，95%CI（1.18 - 7.53））。至于出血性膀胱炎，SLCO1B1（1865 + 4846T＞C）变异基因型是独立保护因素，而年龄较大被认为是独立危险因素（HR分别为0.41，95%CI（0.19 - 0.85）；HR = 2.52，95%CI（1.14 - 5.54））。在常见临床特征与MMF相关SNP和其他并发症之间未发现统计学意义，其他并发症包括II-IV/III-IV级急性GvHD、EB病毒感染、植入综合征和毛细血管渗漏综合征。我们还发现SLCO1B1（597 C＞T）和SLC29A1（-162 + 228 A＞C）变异基因型均是Haplo-HSCT后复发累积发生率的独立因素（HR分别为4.02，95%CI（1.42 - 11.44）；HR = 0.18，95%CI（0.07 - 0.43））。
我们的研究结果突出了MMF相关转运体和代谢酶SNP在移植后并发症发生中的重要性，有助于促进个性化风险评估并改善Haplo-HSCT患者的临床管理。
