Development and Validation of a Nomogram Prediction Model for Subtherapeutic Voriconazole Concentrations in Allogeneic Hematopoietic Stem Cell Transplantation Recipients
10.3969/j.issn.1671-7414.2025.06.014
- VernacularTitle:异基因造血干细胞移植患者伏立康唑血药浓度监测不达标风险预测模型建立及验证
- Author:
Hongchun WANG
1
;
Meng LI
;
Wenli SUN
;
Rui LIU
;
Ying ZHAO
;
Jinyan GUO
;
Guangze LU
;
Yang XUE
;
Ruigeng YANG
;
Lei WANG
Author Information
1. 北京陆道培医院病理和检验医学科,北京 100176
- Publication Type:Journal Article
- Keywords:
allogeneic hematopoietic stem cell transplantation;
voriconazole;
boold drug level;
nomogram;
predic-tion model
- From:
Journal of Modern Laboratory Medicine
2025;40(6):74-79,85
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify determinants of subtherapeutic voriconazole(VRCZ)concentrations in allogeneic hematopoietic stem cell transplantation(allo-HSCT)recipients and to develop/validate a nomogram-based risk prediction model.Methods This study retrospectively analyzed 310 VRCZ therapeutic drug monitoring(TDM)measurements from allo-HSCT recipients at 310 patients who under went allo-HSCT surgery at Hebei Yanda Ludaopei Hospital from October 2022 to October 2024 and received VRCZ for the prevention and treatment of invasive fungal infections before transplantion were selected as the study subjects.Cases were stratified into target-concentration group(0.5～5.0μg/ml)and subtherapeutic group(<0.5μg/ml).Through single factor and multiple factor Logistic regression analysis,indeipendent predictive factors forvecz plasma concentration non-compliance were screened,and a column chart prediction model(NPM)was constructed.The performance of the model was evaluateding area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow(H-L)goodness-of-fit test,and decision curve analysis(DCA).Results Among 310 VRCZ-TDM measurements,71.61%(222/310)achieved target concentrations.Multivariate analysis showed that CYP2C19 intermediate metabolite,daily dose of cyclosporine A(CSA),daily dose of VRCZ,creatinine(Cr)>97 μmol/L,albumin(Alb)and C-reactive protein(CRP)were independent influencing factors for VRCZ blood drug concentration non-compliance(Wald χ2=4.046～13.221,all P＜0.05).The nomogram demonstrated excellent discrimination,calibration(H-L goodness of fit test χ2=2.663,P=0.954),and clinical utility with net benefit across 0.05～0.96 risk thresholds.Conclusion The nomogram incorporating CYP2C19 gene phenotype,daily CSA dosing,daily VRCZ dosing,Cr levels,Alb and CRP provides a validated tool for optimizing VRCZ therapy in allo-HSCT recipients,enabling precision dosing strategies.
