The Impact Of SUFU Polymorphism On GVHD In Children With Thalassemia After Hematopoietic Stem Cell Transplantation

Objective: To explore the impact of suppressor of fused(SUFU)(rs17114808)single nucleotide polymorphism(SNP)on graft-versus-host disease(GVHD)in children with thalassemia after allogeneic hematopoietic stem cell transplantation(HSCT).Methods: Forty-four pediatric patients with thalassemia who underwent allogeneic hematopoietic stem cell transplantation in the Department of Hematology,Affiliated Zhongshan Hospital of Xiamen University from October 2018 to November 2020 were enrolled in this study.The peripheral blood samples were collected before pretreatment and the genomic DNA was extracted.The SNP genotype of SUFU was was analyzed using Taq Man SNP genotyping assay.Using SPSS software to analyze and compare the differences between different genotype groups after transplantation in hematopoietic reconstruction,implantation,total incidence of a GVHD and affected organs,c GVHD and affected organs,CMV and EBV viremia,urinary BK virus infection,bacterial and fungal infection,and overall survival(OS).Results: A total of 44 pediatric patients with thalassemia were included in this study.The deadline for follow-up was February 28,2021,and no data was missing.The median follow-up time lasted for 15 months(83 days ～ 29 months).The median transplant age of all patients was 4 years old(2-11 years old),the average transplantation age is(4.8±2.4)years old.The overall survival rate is 95.4%,and 2cases died in total,the transplant-related mortality rate(TRM)is 4.55%.Among the 44 pediatric patients,n= 13(29.55%)were CC homozygous,n=23(52.27%)were CT and n= 8(18.18%)were TT homozygous,which are significantly different from the genotype frequencies distribution of European individuals.The one-year survival rates of CC group and CT/TT group were 92.31% and 96.77%.Multivariate Logistic analysis showed that the incidence of grade II-IV a GVHD in the CC group was 46.15%,significantly higher than that in the CT/TT group(19.35%),and the difference was statistically significant(p<0.05).There were no significant differences between the two groups in hematopoietic reconstruction,transplanting time of blood cells,total incidence of a GVHD and affected organs,c GVHD and affected organs,CMV and EBV viremia,urinary BK virus infection,bacterial/fungal infection as p>0.05.Conclusion:(1)Allogeneic hematopoietic stem cell transplantation is currently the only cure for transfusion-dependent thalassemia,and the long-term survival rate is over 90%.(2)Among pediatric patients with thalassemia,the frequencies distribution of SUFU(rs17114808)locus genotype is quite different from that of European individuals,which may be related to race.(3)The differences of SUFU(rs17114808)single nucleotide polymorphism(SNP)genotype have no significant effect on the total incidence of GVHD after HSCT in children with thalassemia.Multivariate analysis showed that the presence of SUFU(rs17114808)polymorphism CC genotype in pediatric patients with thalassemia may be an adverse factor that increases the occurrence of grade II-IV a GVHD after transplantation.(4)The occurrence and severity of a GVHD,and different pretreatment regimen are the risk factors for increased urinary BKV replication.