Abstract
Purpose :
To develop a model based on tear levels of a panel of inflammatory mediators to predict the occurrence of ocular chronic Graft Versus Host Disease (cGVHD) before Hematopoietic Stem Cell Transplantation (HSCT).
Methods :
25 patients undergoing HSCT were prospectively followed for up to 3 years. Ocular examination results were recorded, and tears were collected before HSCT and after several time-points. Levels of 19 molecules (EGF, eotaxin 1/CCL11, fractalkine/CX3CL1, IL-1Ra, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-13, IL-17A, IP-10/CXCL10, IFN-γ, VEGF, TNF-α, and RANTES/CCL5) were measured by multiplex bead assay. Multistate models (MSM) considering four states (HSCT, systemic cGVHD, ocular cGVHD, and decease) were used to identify cytokine tear levels that may be associated with the progress of transplanted patients and predict patients’ risk of developing ocular cGVHD. Molecules included in the final multivariable model were reduced by a supervised Principal Components Analysis (PCA). For internal validation of the final MSM, bootstrap re-sampling was used. Model discriminatory ability was determined according to the time-dependent ROC curves, and the corresponding AUC.
Results :
A multistate model was constructed based on fractalkine/CX3CL1, IL-1Ra and IL-6 tear levels, which had a significant influence in the transition between the four different states. This model, based on a new variable built upon combination of these three molecules, displayed an AUC value between 67%-80% throughout follow up, which corresponds to a good discriminatory ability.
Conclusions :
Tear levels of several molecules before HSCT were relatedto individual risk of developing ocular cGVHD. The model based on fractalkine/CX3CL1, IL-1Ra, and IL-6 tear levels before HSCT may allow patient’ stratification according to risk of developing ocular cGVHD prior to transplantation, thus allowing clinicians to adequately manage those high-risk patients.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.