Day-30 IL1RL1, CXCL9 and REG3α are prognostic for survival after mismatched unrelated donor transplantation

While plasma-derived proteins have emerged as potential biomarkers for prognosis after haematopoietic stem cell transplantation (HSCT), there are insufficient data assessing if established proteins interleukin 1 receptor-like 1 (IL1RL1), chemokine ligand 9 (CXCL9) and regenerating islet-derived 3-α (REG3α) retain their utility in the mismatched unrelated donor (MMUD) setting. We assessed their prognostic ability in 53 subjects who received MMUD HSCT from 2016 to 2023 with Day 14 or Day-30 post-HSCT samples in batch using sequential enzyme-linked immunosorbent assay. Elevated Day-30 biomarker concentrations held more prognostic value than Day 14 concentrations. Day-30 CXCL9 value showed association for overall survival (OS) with a hazard ratio of 5.86 (95% confidence interval [CI] 1.21, 28.3, p = 0.03). When stratified by high or lower threshold concentrations, Day-30 concentration revealed differences in 2-year OS for IL1RL1 (p = 0.027), CXCL9 (p = 0.011) and REG3α (p = 0.044). Day-30 area under the curve (AUCt) performance for risk of death by 2 years was 0.86 (95% CI 0.71, 1) for the combination of CXCL9 and IL1RL1, which was superior to any individual biomarker value. In this pilot analysis, Day-30 biomarkers are discriminative for OS at 2 years post-HSCT and may be able to guide future pre-emptive intervention and monitoring.