Percentage of CD56⁺ monocytes at neutrophil engraftment is associated with the incidence of acute graft-versus-host disease

Acute graft-versus-host disease (GVHD) is one of the serious complications following allogeneic hematopoietic stem cell transplantation (HSCT) that leads to non-relapse mortality. Although several biomarkers for acute GVHD have been proposed, no definitive predictive markers are clinically available. Recent studies have shown that a specific subset of peripheral blood monocytes expresses CD56 (neural cell adhesion molecule [NCAM]), particularly under inflammatory conditions; however, their role in allogeneic HSCT remains unclear. Single-cell RNA sequencing of peripheral blood mononuclear cells from patients with acute GVHD identified a unique monocyte subset characterized by an NCAM signature. Prospective multicolor flow cytometry analysis of peripheral blood samples revealed a transient increase in CD56⁺ monocytes at the time of neutrophil engraftment. Gene set enrichment analysis demonstrated pro-inflammatory transcriptome signatures of the CD56⁺ monocyte fraction. Notably, a reduced frequency of CD56⁺ monocytes was significantly associated with a lower incidence of acute GVHD, suggesting their potential as novel predictive cellular biomarkers of acute GVHD.