Predictive Value of Early Measurement of ST2 and REG3 alpha in the Outcome of Haploidentical Stem-Cell Transplantation with Post-Transplant Cyclophosphamide

Context Recent studies have described the importance of Suppressor of Tumorigenicity-2 (ST2) and Regenerating islet-derived 3a (REG3a) serum biomarkers in allogenic stem-cell-transplantation. Only two studies have focused on haploidentical stem-cell-transplantation with post-transplant-cyclophosphamide (haplo-SCT-PCy). Objective Perform an early weekly analysis of ST2 and REG3a biomarkers after haplo-STC-PTCy and study their association with transplant outcomes. Patients Prospective study of 101 consecutive patients who underwent Haplo-SCT-PTCy between 2012-2019 at University Hospital of Salamanca. Design Serial serum samples were collected on days 0, +3, +7, +14, and +21 in 81 patients. ST2 and REG3a serum concentration was stablished by Luminex XMap. The median luminescence levels between groups were compared using the Wilcoxon-Mann-Whitney test. Cut-off points for each cytokine were estimated using the Cutoff Finder application in R. Multivariate Cox proportional hazard models were performed including the most relevant clinical variables. Results Recipient median age 50 years. 70% were performed with reduced intensity conditioning. With a median follow up of 35 months, cumulative incidence of aGVHD III-IV at +180 was 11% and transplant-related mortality at 1-year (TRM-1y) 25%. Overall survival (OS) and progression-free survival (PFS) at 2 years was 64% and 62%. GVHD-free-relapse-free survival at 2 years (GRFS-2y) was 49%. ST2 levels were higher in patients with aGVHD III-IV (day +14), and were associated with higher TRM at 1 year (+7, + 14), lower PFS-2y (+7, +14, +21), lower GRFS-2y (+7, +14, +21), and lower OS-2y (0, +7, +14, +21). Higher levels of REG3a were associated with higher TRM-1y (+7, +14), aGVHD III-IV (+14), lower GRFS (+14), and lower OS-2y (+7). In multivariate analysis for TRM, higher levels of ST2 (+7, +21) and REG3a (+14, +21), prior auto-SCT, and HCT-CI ≥ 3 were statistically significant, while OS was independently related to ST2 (+7, +14) levels and HCT-CI ≥ 3. ST2 (+14) and REG3a (+14) levels were the only variables independently associated to aGVHD III-IV, PFS, and GRFS. Conclusions Our results confirm the significant role of ST2 and REG3a in haplo-SCT-PTCy outcome. We demonstrate, for the first time, its prognostic impact on days +7 and +14. Confirmation in prospective and larger series is required.