Pre-treatment Monocytosis in Pediatric H3K27M-Mutant Gliomas

Abstract Background Systemic immune dysregulation is well-characterized in adult high-grade gliomas but remains underexplored in pediatric population. Among these, H3K27M-mutant diffuse midline gliomas are biologically and clinically distinct, with limited therapeutic options and poor prognosis. While prior studies in medulloblastoma suggest tumor-induced lymphopenia at diagnosis, the immune profile of H3K27M gliomas has not been systematically evaluated. Methods We performed a multicenter retrospective analysis of pretreatment complete blood counts (CBCs) in pediatric patients (≤18 years) with H3K27M-mutant gliomas (n = 37), comparing them to a control cohort with pilocytic astrocytoma (n = 61). Absolute neutrophil count (ANC), monocyte count (AMC), lymphocyte count (ALC), neutrophil-to-lymphocyte count ratio (NLCR), and monocyte-to-lymphocyte ratio (MLR) were evaluated. Patients receiving corticosteroids prior to CBC collection were excluded. Results No significant differences were observed in ANC, ALC, or NLCR between groups. However, the H3K27M group demonstrated significantly elevated AMC (0.70 vs. 0.50 K/μL; p = 0.012) and MLR (0.20 vs. 0.19; p = 0.021) compared to controls. Monocytosis, defined by AMC above age-adjusted means, was present in 78.4% of H3K27M patients versus 46.7% of controls (OR = 4.14, p = 0.003). These findings suggest a distinct pre-treatment immune signature in H3K27M gliomas. Conclusions This is the first study to identify pre-treatment monocytosis and elevated MLR in pediatric H3K27M-mutant gliomas, highlighting a novel systemic immune phenotype with potential implications for biomarker discovery and immunotherapeutic targeting. These results underscore the need for further mechanistic studies and prospective validation in larger, mutation-stratified cohorts.