Donor-derived distinct neutrophil subsets in the G-CSF-mobilized peripheral blood grafts predict acute GVHD development.

Acute graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, although the diverse roles of neutrophils in inflammation and cancer have been recognized, the specific contributions of distinct neutrophil subsets to acute GVHD remain unclear. Herein, we performed a prospective clinical study to investigate the role of distinct neutrophil subsets in G-CSF-mobilized peripheral blood (PB) graft on acute GVHD and to establish statistical prediction models. Our study demonstrated that the early committed neutrophil progenitor (proNeu1) was a risk factor, whereas immature neutrophil (immatureNeu) was a protective factor for grade Ⅱ-Ⅳ acute GVHD. The prediction model based on donor age, proNeu1 and immatureNeu showed significant accuracy for Ⅱ-Ⅳ acute GVHD diagnosis, with an area under the curve (AUC) of 0.782 (95% CI, 0.67-0.88) for the training set and an AUC of 0.771 (95% CI, 0.63-0.91) for the validation set. In addition, Decision Curve Analysis (DCA) indicated that the prediction model possessed high clinical utility. High risk group based on the prediction model is correlated with higher 100-day cumulative incidence of acute GVHD and 1-year cumulative incidence of chronic GVHD. The prediction model based on proNeu1 and immatureNeu subsets provides a risk assessment tool for clinicians to better predict and manage the course of acute GVHD. Moreover, we demonstrated that donor-derived CD10-immature neutrophils in the G-CSF-mobilized PB grafts as an immunoregulatory neutrophil were associated with attenuated acute GVHD, potentially through increased Reactive Oxygen Species (ROS) levels.