Peripheral immune indicators and their predictive value in disease progression or relapse of pediatric Langerhans cell histiocytosis.

OBJECTIVE

Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm in which the inflammatory microenvironment plays a crucial role in the development and progression of disease. The prognostic value of circulating lymphocyte subsets and cytokines remains uncertain.

METHODS

The authors retrospectively analyzed baseline peripheral lymphocyte subsets and serum cytokines in 330 consecutive pediatric patients. Immune profiles were compared across disease extent, clinical events, and biological features. Prognostic associations with progression-free survival (PFS) were tested using univariable and multivariable models.

RESULTS

Peripheral immune profiles varied with disease extent. Patients with multisystem risk-organ involvement (MS RO+) had fewer total T and Th1 cells, more CD4⁺ T and B cells, and higher IL-6, IL-10, and IFN-γ. Patients who progressed or relapsed showed a similar pattern, and non-survivors had particularly high IL-10. In the first-line cohort, the proportions of T, B, CD4⁺ T, CD8⁺ T, and Th1 cells, ratios of CD4/CD8 and Th1/Th2, and levels of IL-6, IL-10 predicted progression/relapse, and Youden-derived cut-offs dichotomized with distinct PFS. On multivariable Cox, IL-6, IL-10, Th1/Th2 ratio, RO status, and week-6 responses were independent predictors, and a nomogram model with good predictive capability was formed. IL-10 remained independently prognostic in multisystem LCH; the immune indices were not prognostic in single-system LCH. External validation in 103 patients confirmed risk stratification and model performance with well-calibrated PFS estimates.

CONCLUSION

Baseline peripheral lymphocyte subsets and cytokines carried prognostic information in pediatric LCH. The IL-6, IL-10, and Th1/Th2 profile supported risk stratification and may inform treatment planning.