Assessment of risk factors for acute graft-versus-host disease post-hematopoietic stem cell transplantation: a retrospective study based on a proportional odds model using a nonlinear mixed-effects model

Abstract

Background: Acute graft- versus-host disease (aGVHD) is a major complication following hematopoietic stem cell transplantation (HSCT). Objective: This study aimed to explore the risk factors for the incidence of aGVHD in patients post-HSCT. Design: This was a retrospective study. Methods: A total of 407 patients were enrolled. The patients’ data were recorded from the medical records. The exposure of cyclosporine was estimated based on a population pharmacokinetics model. The occurrence of aGVHD was clinically graded and staged in severity from grades I to IV. A proportional odds model that estimated the cumulative probabilities of aGVHD was used to analyze the data using a nonlinear mixed-effects model. Then, the model parameters and plausibility were evaluated by bootstrap and visual predictive checks. Results: The typical probabilities were 18.9% and 17.9% for grade II and grades III–IV, respectively. The incidence of grade II and grade III–IV aGVHD for human leukocyte antigen (HLA) haplo sibling donor patients was higher than that for HLA-matched donor patients. The incidence of grade II and grade III–IV aGVHD decreased with increasing early cyclosporine trough concentration; however, cyclosporine exposure was not associated with the incidence of aGVHD. Conclusion: HLA matching and early cyclosporine trough concentration were important factors for the occurrence of aGVHD.