Infused PMN-MDSCs from G-CSF–mobilized PBSCs protect against II–IV° acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells. Their role in modulating acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. This study aimed to investigate the impact of MDSC levels in granulocyte colony-stimulating factor (G-CSF)–mobilized peripheral blood stem cell (PBSC) grafts on the incidence of II–IV° aGVHD. We retrospectively analyzed 170 allo-HSCT recipients. Employing an exposure-based analytical framework, patients were stratified into high- and low-dose groups based on the infused dose of polymorphonuclear MDSCs (PMN-MDSCs). In Fine-Gray competing risk analyses, a high dose of PMN-MDSCs per kilogram (> 17.5 × 10⁶/kg) was an independent protective factor against aGVHD (subdistribution hazard ratio [sHR] 0.25, 95% CI 0.07–0.88, P = 0.039). A clinically applicable optimal cut-off was identified at 11.3 × 10⁶/kg. Patients receiving a PMN-MDSC dose > 11.3 × 10⁶/kg had significantly superior 300-day overall survival (92.4% vs. 74.9%, P = 0.005) and GVHD-free relapse-free survival (76.3% vs. 40.4%, P < 0.001) compared to the low-dose group. In the malignant disease subset (n = 147), a high dose of the activated LOX-1⁺ PMN-MDSC subset was associated with a markedly lower cumulative incidence of relapse (1.37% vs. 11.42%, P = 0.015). Longitudinal monitoring revealed that the peak incidence of aGVHD (median day + 29) closely followed the peak and subsequent decline of circulating MDSC levels. The absolute dose of PMN-MDSCs in G-CSF-mobilized grafts is an independent determinant of II–IV°aGVHD risk and survival outcomes, with a defined threshold of 11.3 × 10⁶/kg. These findings position PMN-MDSC dose as a promising biomarker for risk stratification and a potential lever for optimizing graft composition in allo-HSCT.