儿童异基因造血干细胞移植后肠道急性移植物抗宿主病危险因素分析及风险预测模型的建立

Analysis and Modeling of Risk Factors for Children with Intestinal Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

目的:进行儿童异基因造血干细胞移植(allo-HSCT)后肠道急性移植物抗宿主病(a GVHD)相关因素分析,并建立儿童allo-HSCT后肠道a GVHD的预测模型。方法:回顾性分析2018年2月至2021年9月于新疆维吾尔自治区人民医院血液科就诊并行allo-HSCT的62例儿童患者的临床资料,按a GVHD国际联盟(MAGIC)分级标准评估肠道a GVHD,通过10折交叉验证LASSO回归筛选变量,建立儿童allo-HSCT后肠道a GVHD的预测模型。结果:62例患儿中共有33例(53.2%)发生肠道a GVHD,其中25例为II度,8例为Ⅲ-IV度。通过10折交叉验证LASSO回归筛选变量,结果显示:有意义的变量包括少数民族(OR=7.229;95%CI:2.337-22.354)、PLT(OR=0.971;95%CI:0.932-0.993)、UA(OR=0.971;95%CI:0.935-0.988)、CRP(OR=1.217;95%CI:1.053-1.545)、病毒感染(OR=10;95%CI:3.021-32.668)与儿童肠道a GVHD独立相关(均P<0.05)。根据上述变量构建预测模型,计算该模型的受试者工作特征曲线(ROC曲线)下面积AUC值为0.983(0.966-1),布里尔分数(Brier Score)为0.055,评估该模型具有较高的区分度及校准度。结论:少数民族、低PLT、低UA、高CRP、病毒感染与儿童肠道aGVHD独立相关,应早期对此类高风险患儿提高重视。

Objective:To analyze factors associated with intestinal acute graft-versus-host disease(aGVHD)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children and to develop a prediction model for intestinal aGVHD after allo-HSCT in children.Methods:The clinical data of 62 children who underwent allo-HSCT at the Department of Hematology of the People's Hospital of Xinjiang Uygur Autonomous Region from February 2018 to September 2021 were retrospectively analyzed.Intestinal aGVHD was evaluated according to the Mount Sinai Acute GVHD International Consortium(MAGIC)grading criteria,the variables were screened by LASSO(least absolute shrinkage and selection operator)regression analysis with 10-fold cross-validation,and developed a model for predicting intestinal aGVHD after allo-HSCT in children.Results:A total of 33(53.2%)of the 62 children developed intestinal aGVHD,of which 25 were degree II and 8 were degree III-IV.The results of screening variables by 10-fold crossvalidated LASSO regression showed that the significant variables included ethnic minorities(OR=7.229;95%CI:2.337-22.354),platelet(PLT)(OR=0.971;95%CI:0.932-0.993),uric acid(UA)(OR=0.971;95%CI:0.935-0.988),C-reactive protein(CRP)(OR=1.217;95%CI:1.053-1.545),and viral infection(OR=10;95%CI:3.021-32.668),and these variables were independently associated with intestinal aGVHD in children(all P<0.05).A prediction model was constructed based on above variables.The area under the receiver operating characteristic(ROC)curve(AUC)of the model was calculated,and the AUC value was 0.985(0.966-1),the Brier score was 0.055.The evaluation showed that the model has a high degree of discrimination and calibration.Conclusion:Ethnic minorities,low PLT,low UA,high CRP,and viral infections are independently associated with intestinal aGVHD in children,and early attention should be paid to these high-risk children.