Donor Neutrophil Subsets in G-CSF Mobilized Peripheral Blood Stem Cell to Predict the Risk of Agvhd

Purpose: Recently, a few studies began to focus on the role of neutrophil subsets in the immune tolerance; however, the role of these subgroups in acute graft versus host disease (aGVHD) is unclear. In our study, we explore the effect of neutrophil subsets in G-CSF mobilized peripheral blood stem cell transplants on the occurrence of aGVHD and establish a prediction model for the occurrence of II-IV aGVHD within 100 days after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients and Methods: A prospective cohort trial was performed in our hospital from December 2023 to March 2024. The proportion of neutrophil subsets in the donor-derived G-CSF-mobilized peripheral blood stem cell grafts, including: neutrophil progenitor 1 (proNeu1), neutrophil progenitor 2 (proNeu2), neutrophil precursor cells (preNeu), immature neutrophils (immatureNeu), and mature neutrophils (matureNeu), were detected by flow cytometry. Univariate logistic regression and restricted cubic spline (RCS) were used to screen variables related to the onset of aGVHD. A multivariate logistic regression equation was constructed with the screened variables to establish a prediction model, and the prediction performance of the model was evaluated. This trial is registered with ClinicalTrials.gov (NCT 06394895) and is completed. Results: A total of 139 patients were enrolled in the study, of which 98 patients were randomly selected as the training cohort and 41 patients as the validation cohort. We found that the matureNeu ratio, proNeu2 ratio, donor type and donor age in the graft were independent influencing factors for II-IV aGVHD. Based on these four variables, we established a prediction model for the risk of II-IV aGVHD.In the prediction model,the area under the receiver operating characteristic (ROC) curve (AUC) of the model was 0.789 and 0.777 in the training set and validation set, respectively. The optimal cutoff value of this prediction scoring system was 0.4. A prediction score greater than 0.4 was defined as a high-risk population for II-IV aGVHD. The 100-day cumulative incidence of grade II-IV aGVHD was 19.1% (95% CI 9.2-27.9%) and 60.6% (95% CI 47.4-70.4%) in the high- and low-risk groups of this cohort, respectively (P < 0.0001). Conclusion: The proportion of matureNeu subgroup, proNeu2 subgroup, donor type and donor age in peripheral blood stem cell transplants are independent influencing factors for II-IV aGVHD after allo-HSCT. The prediction model based on these variables has good predictive ability and can intuitively and quickly identify the high-risk population for II-IV aGVHD.