Acute Graft-Versus-Host Disease (aGVHD, Non-Relapse Mortality) Risk Prediction Assay: Validation and Initial Reference Lab Experience

Abstract

Introduction aGVHD affects 40% to 60% of hematopoietic cellular transplant (HCT) patients, targeting the skin, liver, and gastrointestinal tract with a median onset approximately 1 month after transplant. In 2017, an interpretive algorithm based on serum ST2 and REG3α levels was clinically validated (JCI Insight 2017;2(3):e89798). Objectives This report details validation, inter-lab correlation and initial results from clinical analysis. Methods ST2 and REG3α levels were analyzed in serum using enzyme immunoassays. ST2 and REG3α values are analyzed through an equation to provide an index value that can be used for predicting non-relapse mortality and aGVHD risk for pre-symptomatic (low/high risk), symptomatic onset (low/medium/high risk) and post treatment (low/high risk) HCT patients. Results were compared with the research lab where the equation was established (Mount Sinai Medical Center, MSMC). Results The inter-assay precision ranged from 12 to 26 %CV for ST2 and REG3a, while those for the calculated indices ranged from 17 to 18%. Accuracy was compared against biomarker values and indices reported by MSMC for 106 serum samples. Among samples with biomarker concentrations within the assays' measuring range, the relative error was Conclusions The aGVHD index and its component input assays, ST2 and REG3a, were validated for clinical use. Notably, excellent concordance was observed on a large sample set (106 sera) with MSMC. In addition, initial results indicate that the aGVHD index may prove useful for risk-stratifying HCT patients.