The utility of biomarkers in acute GVHD prognostication.

The clinical severity of acute graft-versus-host disease (GVHD) at its onset is a modest predictor of long-term patient outcomes. Robin et al recently published a single-center study from Hopital Saint -Louis (HSL) evaluating the utility of blood biomarkers in acute GVHD prognostication.1 The authors also developed an HSL clinical model to predict outcomes that included 3 clinical variables: liver involvement, age >= 50 years, and grade 3 or 4 acute GVHD. They then evaluated the value of bio-markers when added to the HSL clinical model using several different techniques, including Delta C-index and decision curve analyses (DCAs). The authors concluded that the benefit of the addition of bio-markers to the HSL clinical model was marginal in predicting GVHD outcomes. We performed analyses, identical to those reported by Robin et al, among 710 patients who received hematopoietic cell transplantation (HCT) between January 2015 and December 2021, with data and samples from the Mount Sinai Acute GVHD International Consortium (MAGIC) database and bio-repository (supplemental Table 1; 44 of 710 patients [6%] were included in the original publication).2 The same eligibility criteria (aged 18-75 years, grade 1-4 acute GVHD systemically treated with at least 1 mg/kg of steroids daily) were used for both analyses (supplemental Table 2). We collected clinical data, measured the serum concentrations of suppression of tumorigenicity 2 (ST2) and regenerating islet-derived 3-alpha (REG3 alpha) (referred to as panel 2 by Robin et al1) at systemic treatment initiation, and computed the respective MAGIC algorithm probability (MAP) scores, as previously described.2,3 We followed the same statistical methodology used in the study by Robin et al to compute the C -index, Delta C-index with 1000 bootstrap resamples to derive confidence intervals, and DCAs.1 Patients who were classified to be at high risk based on the HSL clinical model (liver involvement or age >= 50 years old, with grade 3-4 acute GVHD [126 of 710 (18%)]) experienced a threefold increase in nonrelapse mortality (NRM) compared with patients at low risk (45% vs 14%; P < .001; Figure 1A); these results were in agreement with those reported by Robin et al (Figure 1A as previously