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. 2023 Oct 21:14:20406207231205406.
doi: 10.1177/20406207231205406. eCollection 2023.

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

Ling Xue  1   2 , Lin Song  1   3 , Xun Yu  1 , Xiao Yang  4 , Fan Xia  1 , Xiaoliang Ding  1 , Chenrong Huang  1 , Depei Wu  5 , Liyan Miao  6
Affiliations

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

Ling Xue et al. Ther Adv Hematol. .

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.

Keywords: acute graft-versus-host disease; cyclosporine; hematopoietic stem cell transplantation; proportional odds model; risk factor.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Flow chart of patient selection.
Figure 2.
Figure 2.
Logistic regression of the probability of different grades of aGVHD versus HLA for the visual predictive check. The median (circle) and 95% CIs (shaded area) obtained from 500 simulations are shown. In addition, the actual observations with 95% CIs are shown. aGVHD, acute graft-versus-host disease; CI, confidence interval; HLA, human leukocyte antigen.
Figure 3.
Figure 3.
Logistic regression of the probability of different grades of aGVHD versus average CON_CsA14 for the visual predictive check. The median (circle) and 95% CIs (shaded area) obtained from 500 simulations are shown. In addition, the actual observations with 95% CIs are shown. aGVHD, acute graft-versus-host disease; CI, confidence interval; CON_CsA14, CsA trough concentration of the first 14 days post HSCT.
Figure 4.
Figure 4.
Average CsA trough concentration in the first 14 days post-HSCT of different grades of aGVHD for different HLAs. aGVHD, acute graft-versus-host disease; CsA, cyclosporine; HLA, human leukocyte antigen; HSCT, hematopoietic stem cell transplantation.
See this image and copyright information in PMC

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