Immunophenotypic Profiling of Lymphocyte Subsets in Children and Adolescents With Acute Lymphoblastic Leukaemia: Immune Dysregulation Before and After Remission.

BACKGROUND: Acute lymphoblastic leukaemia (ALL) in children is often associated with immune dysfunction, including alterations in regulatory T cells (Treg), impaired T-cell activation, and disrupted natural killer (NK) cell function. ALL comprises immunophenotypically heterogeneous entities, primarily B-cell ALL (B-ALL) and T-cell ALL (T-ALL). However, the dynamics of Treg subsets and their relationship with broader immune alterations across treatment stages remain insufficiently characterised.

METHODS: In this prospective case-control study, peripheral blood samples were analysed from 31 children with newly diagnosed ALL (pre-remission), 20 patients in remission and 24 healthy controls (HCs). Multiparameter flow cytometry was used to assess T-cell receptor (TCR) αβ+/γδ+ T cells, CD4+/CD8+ T-cell subsets, B cells, NK and NKT-cell populations, CD69 activation markers, and classical and memory Treg subsets.

RESULTS: At diagnosis, patients showed significant reductions in TCR αβ+ and γδ+ T cells, CD4+ T-helper cells and CD69 activation, alongside increased CD8+ T cells and NKT cells. Classical and memory Treg cells were significantly expanded in the pre-remission group. Following remission, TCR expression and CD3+ T-cell frequencies approached levels observed in HCs, and CD4+CD69+ activation improved. However, CD56bright NK cells remained reduced, and B-cell depletion persisted in both ALL groups.

CONCLUSION: Paediatric ALL is characterised by marked immune dysregulation involving expanded Treg populations and impaired lymphocyte activation. Although partial immune recovery occurs after remission (AR), persistent abnormalities in NK-cell and B-cell compartments suggest incomplete immune reconstitution.