Dynamic Peripheral Blood Lymphocyte Subsets as Predictive Biomarkers for Langerhans Cell Histiocytosis in Children

Abstract

Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm, immune system dysfunction may attribute to the cause of LCH. There is no standard prognosis evaluation system for LCH in children. We investigated the prognosis predictive value of peripheral lymphocyte subsets in childhood LCH patients.Methods: A cohort of 79 childhood LCH patients was retrospectively studied. The prognosis predictive significance of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, NK cells, B cells and CD4/CD8 ratio were analyzed.Results: After 6-week induction therapy, the percentage of CD3+ T cells, CD3+CD4+ T cells and CD4/CD8 ratio were significantly increased, while CD3+CD8+ T cells and B cells were decreased. CD3+CD8+ T cells and B cells were closely related to BRAF V600E and MAP2K1 mutation. ∆CD3+ T cells, ∆CD3+CD4+ T cells, ∆CD3+CD8+ T cells, ∆NK cells and ∆B cells were related to treatment efficacy. As for organ involvements, ∆CD3+ T cells and ∆CD3+CD8+ T cells were related to liver involvement, ∆CD4/CD8 ratio was related to CNS involvement ∆CD3+ T cells and ∆B cells were related to BRAF V600E mutation, while ∆CD3+CD4+ T cells was related to MAP2K1 mutation. Furthermore, increased ∆CD3+ T cells, decreased ∆CD3+CD4+ T cells, decreased ∆CD3+CD8+ T cells, decreased ∆NK cells and increased ∆B cells were predictors for superior PFS, while increased ∆CD3+ T cells, decreased ∆CD3+CD8+ T cells and decreased ∆NK cells were predictors for superior OS. In addition, multivariate Cox regression analysis showed that ∆CD3+ T cells and ∆CD3+CD8+ T cells were independent prognostic factors for PFS.Conclusions: The peripheral lymphocyte subsets including CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, NK cells and B cells might be promising predictive indicators for LCH in children.