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Percentage of CD56+ Monocytes at Neutrophil Engraftment is Associated with the Incidence of Acute Graft-versus-host Disease

Researchers at Nagoya University Graduate School of Medicine and collaborating hospitals in Japan have identified a peripheral blood monocyte subset that may serve as an early cellular biomarker for acute graft-versus-host disease after allogeneic HSCT. In this study, published in Annals of Hematology, the investigators show that CD56-positive monocytes rise transiently around neutrophil engraftment and that higher levels at this time point are associated with a greater subsequent incidence of acute GVHD. The main finding is that these CD56-positive monocytes appear to represent a distinct pro-inflammatory myeloid population that emerges before clinical GVHD and could help risk-stratify patients earlier than symptom-based diagnosis alone.

Acute GVHD remains a major cause of non-relapse mortality after allogeneic transplantation, and although serum biomarkers such as ST2 and REG3α have been studied, reliable early cellular predictors are still lacking. To address this, the authors first analyzed a public single-cell RNA sequencing dataset of peripheral blood mononuclear cells from patients with and without acute GVHD and identified monocyte-enriched clusters with an NCAM/CD56-associated interaction signature. The authors then conducted a prospective flow cytometry study in 28 enrolled transplant recipients, of whom 24 were evaluable after excluding 4 with engraftment failure or early death before neutrophil engraftment.

Clinically, receiver operating characteristic analysis identified a CD56-positive monocyte cutoff of 6.3% at neutrophil engraftment for predicting later acute GVHD, with an AUC of 0.65 (95% CI 0.42–0.88). Patients below this threshold had a significantly lower cumulative incidence of acute GVHD (P=0.047), and the same pattern held for grade II–IV acute GVHD (P=0.039). The median interval from monocyte assessment at engraftment to GVHD onset was 10 days, with a range of 2–65 days. Transcriptionally, CD56-positive monocytes showed higher NCAM1 expression with a log2 fold change of 5.04 and enrichment of TNFα signaling, inflammatory response, lipopolysaccharide-treated monocyte, and Toll-like receptor signaling gene sets, supporting a pro-inflammatory phenotype. Among the 24 evaluable patients, median age was 41.5 years, 95.8% received myeloablative conditioning, and graft sources included bone marrow (37.5%), peripheral blood (33.3%), and cord blood (29.2%). These findings demonstrate that a simple flow cytometric measurement at engraftment could identify patients at higher risk of acute GVHD before symptoms develop, potentially allowing earlier surveillance or pre-emptive intervention.

Reference:

Hashimoto K, Sato T, Ishikawa Y, et al. Percentage of CD56+ monocytes at neutrophil engraftment is associated with the incidence of acute graft-versus-host disease. Ann Hematol. 2026;105(4):153. Published 2026 Mar 2. http://doi.org/10.1007/s00277-026-06897-2