Ferritin as a Pre-Transplant Biomarker for Post-Transplant Outcomes in Allogeneic Stem Cell Transplantation Using Post-Transplant Cyclophosphamide.

[BACKGROUND] Iron overload, indicated by elevated ferritin, is a potentially modifiable risk factor in allogeneic hematopoietic cell transplantation (allo-HCT); however, its prognostic value remains uncertain.

[OBJECTIVES] We evaluated whether pre-transplant ferritin (pre-TF) levels are associated with allo-HCT outcomes, including overall survival (OS), disease-free survival (DFS), relapse incidence, and GVHD incidence.

[STUDY DESIGN] We retrospectively analyzed 682 allo-HCT recipients transplanted between 2019 and 2022, with a median follow-up of 37 months. Pre-TF was measured at a median of 17 days before allo-HCT. A time-dependent receiver operating characteristic analysis for 2-year OS defined the optimal pre-TF cut-off of 2209 µg/L (AUC: 0.53, sensitivity 35%, specificity 75%). Propensity score matching (PSM) was performed at a 2:1 ratio (controls:cases, caliper 0.2), balancing pre-transplant characteristics to yield a matched cohort of 417 patients.

[RESULTS] The median pre-TF was 1159 µg/L. After PSM, 278 patients (66.7%, n = 278/417) had low pre-TF (< 2209 µg/L), and 139 (33.3%) had high pre-TF (≥ 2209 µg/L). High pre-TF was associated with a higher relapse incidence (HR: 1.484, 95% CI, 1.019 to 2.160, P = .039) and a lower incidence of moderate or severe chronic graft-versus-host disease (cGvHD) (HR: 0.501, 95% CI, 0.298 to 0.843, P = .009). OS did not differ after PSM, and was primarily influenced by HCT-CI and conditioning intensity. No differences were observed in graft dynamics, immune reconstitution, or infections. An exploratory AML-specific analysis (cut-off of 2885 µg/L) showed similar patterns for DFS and cGvHD.

[CONCLUSION] Elevated pre-transplant ferritin identifies allo-HCT patients at a higher relapse risk and lower risk of cGvHD. These results suggest that ferritin may be associated with immunomodulatory effects that attenuate the graft-versus-leukemia effect while reducing graft-versus-host disease, although this requires further investigation. Clinically, ferritin may serve as a simple and accessible risk biomarker, warranting prospective validation with disease-specific thresholds and integration of functional iron measures.