Dynamic Changes in Peripheral Blood Lymphocyte Subset Counts and Functions in Children with B-Cell Acute Lymphoblastic Leukemia during and after Chemotherapy

Background: B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignant tumor in children. This study aimed to investigate the lymphocyte subsets, their activities and dynamic changes during and after chemotherapy in children wiht B-ALL.

Methods: Peripheral blood samples were prospectively and cross-sectional collected from B-ALL children at different treatment time points (50 cases at initial diagnosis, 40 cases after induction, 20 cases at the beginning of maintenance, 15 cases at 61 weeks, the middle of maintenance, 20 cases at the end of treatment, 18 cases at 5-year follow-up) and healthy control children. T, B and NK lymphocyte subsets, immunophenotypes and functions were detected by flow cytometry.

Results: Compared with healthy controls, T cells in patients newly diagnosed with B-ALL were in a state of inhibition, senescence and exhaustion. The percentages of CD4⁺, CD4/CD8, γδ T, CD4⁺Tnaive as well as CD8⁺Tnaive were significantly decreased (P < 0.05). The percentages of CD8⁺, Tregs, CD4⁺Tcm, CD8⁺Tem, CD4⁺PD-1, CD4⁺TIM-3, CD8⁺PD-1 and CD8⁺TIM-3 were significantly increased (P < 0.05). The levels of IFN-γ, IL-4 and IL-2 were significantly lower. NK and NKT cells in B-ALL children were in a state of inhibition, which mainly showed that the percentage of NK and NKT was significantly decreased, and the activator receptor NKP46 and NKG2D were significantly decreased (P < 0.05). After induction therapy, the percentage of B cells decreased significantly (P=0.000), and T cells and NK cells had a partial recovery (P < 0.05). When entering to maintenance therapy, T, B, NK cell percentage and T cell function of patients were the most severely impaired, and then gradually recovered. Till to the end of treatment, the function of lymphocytewas inhibited. At 5 years follow-up, the counts and functions of B and NK cells recovered, but that of T cells did not recover completely.

Conclusions: The absolute counts and functions of T cells and NK cells, which were significantly lower in children with B-ALL, gradually recovered after chemotherapy. Detecting the counts and functions of peripheral blood lymphocytes is important for identifying new prognostic markers of ALL, guiding to prevent infection and administering effective immunotherapy.

No relevant conflicts of interest to declare.