Abstract
Introduction: Acute Myeloid Leukemia (AML) is a malignant hematologic neoplasm with an unfavorable prognosis. The Wilms’ tumor gene (WT1) is a key prognostic biomarker in AML, showing longitudinal patterns that may predict survival outcomes after transplantation. This study aimed to jointly model the longitudinal changes in the WT1 gene expression and the survival time of AML patients using a Bayesian approach.
Methods: This retrospective cohort study used data from 319 AML patients who underwent allo-HSCT and were followed up between 2008 and 2019 at the Hematology Clinic of Shariati Hospital in Tehran. For data analysis using Bayesian joint longitudinal and survival modeling, a random effects model was used for the longitudinal submodel, and a generalized hazard regression model with a Burr XII (BXII) baseline hazard function was used for the survival submodel.
Results: Results demonstrated that a higher baseline WT1 level was significantly associated with reduced survival, increasing the hazard of death by 47.4% (HR=1.474, 95% CI: 1.325-2.052). The longitudinal submodel revealed that WT1 expression significantly increased by 0.169 times in patients with acute Graft-versus-Host Disease (aGVHD) and by 1.103 times in those who relapsed. The survival submodel confirmed that increased age (HR=1.309), disease relapse (HR=1.955), and donor type other relative and unrelated compared to sibling (HR=1.975 and HR=1.479, respectively) were predictors of worse survival.
Conclusion: In conclusion, elevated WT1 expression at transplantation is a critical negative prognostic indicator in AML. Monitoring this biomarker helps identify high risk patients and can guide pre-transplant therapeutic strategies to improve survival outcomes.