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.