Differential Expression of Immunity Related Genes Can Predict Moderate-Severe Chronic GvHD Early after Myeloablative Hematopoietic Stem Cell Transplantation.

Introduction Chronic graft versus host disease is the major cause of poor outcomes after allogeneic hematopoietic cell transplantation (HCT). Clinically significant moderate-severe chronic GvHD (cGvHD) rarely shows a sustained complete response to immunosuppressive drugs and non-responders either die or suffer long-term. Early and accurate prediction of ensuing cGvHD can help identify high risk patients to make preemptive treatment possible. In the present study, we retrospectively analyzed the transcriptome of immunity related genes at one month post-transplant with the aim to identify a potential early and accurate predictor of clinically significant cGvHD. Methods An adult retrospective cohort of 73 human leukocyte antigen (HLA) matched myeloablative allogeneic HCT recipients were included. All patients received 4.5 mg/kg antithymocyte globulin as GvHD prophylaxis. Diagnosis of cGvHD was based on National Institutes of Health consensus criteria with the median day of diagnosis being 126 days. Total RNA extracted from cryopreserved peripheral blood mononuclear cells at one month post-transplant was used to run a gene expression CodeSet profiling of 594 immunity related genes including 15 internal reference genes using Nanostring Technology. Benjamini Hochberg procedure was used to calculate the P value and the false discovery rate (FDR) of differentially expressed genes. Results A set of 12 differentially expressed genes with a Benjamini Hochberg P-value (BHP) of 7 in this panel of 12 genes was able identify patients with high risk of developing mod-severe cGVHD with a sensitivity of 79% and specificity of 88% (AUC = 0.88, P Conclusion The robust and rapid technique of Nanostring based transcriptome profiling identified a gene panel consisting of 12 genes for an early prediction of moderate-severe cGVHD (one month) with high sensitivity and specificity. A precision medicine approach of preemptive treatment of cGVHD can be possible using this study leading to improved outcomes of HCT.