CD52+ cells are associated with faster short-term neutrophil recovery in mobilized hematopoietic stem cell transplant

Introduction Delayed neutrophil recovery after peripheral blood hematopoietic stem cell transplantation (PBHSCT) remains a leading driver of post-transplant infections and is closely associated with adverse outcomes. Current graft potency assessments rely on bulk CD34+ cell counts, which fail to resolve functional heterogeneity within the CD34+ compartment and poorly predict short-term engraftment outcomes.Objectives We aimed to identify a CD34+ subpopulation that robustly predicts accelerated neutrophil recovery, define its biological basis, and evaluate its clinical utility for optimizing PBHSCT management.Methods We profiled G-CSF-mobilized CD34+ grafts from 30 paired HLA-matched healthy donors and acute leukemia recipients across discovery (n = 9) and validation (n = 21) cohorts using single-cell RNA sequencing (scRNA-seq) and multicolor flow cytometry. Findings were validated via in vitro multi-lineage differentiation, single-cell cloning, xenotransplantation, and rigorous statistical approaches including bootstrap resampling and robust regression.Results We identified Lin-CD34+ CD52+ cells as a myeloid-primed subpopulation whose dose correlated strongly with shortened interval to neutrophil recovery (INR) than bulk CD34+ or canonical HSPC subsets (R = -0.87, p 9/L) 2 days earlier than low-dose counterparts. Mechanistically, Lin-CD34+ CD52+ cells exhibited hyperactivated SPI1/PU.1 signalling and a G-CSF-induced pro-migratory signature absent in steady-state bone marrow CD34+ cells. Crucially, CD52 blockade did not alter progenitor function, confirming CD52 as a passive surrogate marker of myeloid priming rather than an active differentiation driver.Conclusion Our findings establish CD52 as a novel, clinically actionable biomarker for PBHSCT graft potency, supporting potency-informed graft selection and individualized transplant planning to accelerate neutrophil recovery and improve patient outcomes.