Prehematopoietic Stem Cell Transplantation Tear Cytokines As Potential Susceptibility Biomarkers For Ocular Chronic Graft-Versus-Host Disease

PURPOSE. To determine if cytokine tear levels before hematopoietic stem cell transplantation HSCT) can help anticipate the occurrence of ocular chronic graft-versus-host disease (cGVHD).METHODS. In this pilot study, 25 patients undergoing HSCT were followed prospectively for <= 43 months. After ocular examinations, tears were collected before HSCT. Levels of 19 cytokines (epidermal growth factor [EGF], eotaxin 1/CCL11, fractalkine/CX3CL1, IL-1R alpha, IL1 beta, IL-2, IL-4, IL-5, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-13, IL-17A, IP-10/CXCL10, IFN-c, VEGF, TNF-alpha, and RANTES/CCL5) were measured by multiplex bead assay. A multistate model (MSM) based on four states (HSCT, systemic cGVHD, ocular cGVHD, and death) was developed to identify cytokines associated with each transition probability. Molecules included in the final multivariable model were selected by a supervised principal components analysis. Bootstrap resampling internally validated the final MSM. Model discriminatory ability was determined by time-dependent receiver operating characteristic curves and the corresponding area under the curve (AUC).RESULTS. The final model, based on fractalkine, IL-1R alpha, and IL-6 tear levels, accurately influenced the transition between the four different states. The AUC for this model, based on a new variable built upon the combination of these three molecules, was 67% to 80% throughout follow-up and, thus, had good discriminatory ability.CONCLUSIONS. In this prospective study, a model based on pre-HSCT tear levels of the inflammatory molecules fractalkine, IL-1R alpha, and IL-6 had good prognostic ability for the development of ocular cGVHD after HSCT. These cytokines potentially could act as susceptibility biomarkers for the development of this disease after HSCT.