A panel of ST2, Reg3α, Elafin, and TNFR1: Predictive value for acute GvHD and outcomes in hematological malignancy patients post allo-HSCT

Allogeneic hematopoietic cell transplantation (allo-HSCT) is an essential therapeutic modality hematological malignancies, but acute graft-versus-host disease (aGvHD) persists as a leading cause of non-relapse mortality (NRM) . Cytokine biomarkers have already been used to predict aGvHD and outcomes. However, the standard guidelines for aGvHD biomarker panels remain controversial. We retrospectively analyzed the association of a biomarker panel (suppressor of tumorigenesis 2 [ST2], regenerating islet-derived 3 α [REG3α], Elafin, and tumor necrosis factor 1 [TNFR1]) in serum with the onset of 100-day aGvHD, 12-month NRM, and overall survival (OS) in 141 hematological malignancies patients at 19 ± 5 days after allo-HSCT from January 2022 to August 2023. Multivariable analysis showed that ST2 (P < .001) were strongly correlated with aGvHD, and TNFR1 was significantly associated with 12-month NRM and OS (P < .001). The panel of ST2, REG3α, Elafin, and TNFR1 demonstrated the best performance in diagnosis of 100-day aGvHD (area under the curve [AUC] = 0.79) and in the prediction of 12-month NRM (AUC = 0.74) and OS (AUC = 0.71). The 4-biomarker panel's risk classification predicted the 12-month cumulative incidence of NRM (43% vs 11%, P < .001) and 12-month OS (51% vs 82%, P < .001) for the high-risk and low-risk groups, respectively. Our results suggest that a combination of ST2, REG3α, Elafin, and TNFR1 is an excellent biomarker predictive panel for aGvHD diagnosis and outcomes after allo-HSCT.