Alterations in CD8+ T cells, CD4+ subsets, NK cells, and immune checkpoint expression in Mexican children newly diagnosed with pre-B ALL, and their relationship with thrombocytopenia at diagnosis and myelotoxicities such as neutropenia, and infections during the induction phase of chemotherapy

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Background. Acute lymphoblastic leukemia (ALL) is the most common childhood cancer globally. While high-income countries report 5-year survival rates exceeding 80%, low- and middle-income countries (LMICs) face reduced rates due to treatment-related mortality (TRM). Chemotherapy-induced myelotoxicities are significant contributors, particularly during the induction phase. Immune parameters, including T-helper (Th) cells, regulatory T cells (Tregs), and natural killer (NK) cells, may influence TRM, yet their roles remain poorly understood in LMIC settings. Methods. This prospective study evaluated 10 children newly diagnosed with pre-B ALL at a tertiary care center in Mexico. Flow cytometry and cytokine bead arrays assessed CD8+ T cells, CD4+ subsets, NK cells, and immune checkpoint markers at diagnosis, during induction. Myelotoxicities and complications, including infections and thrombocytopenia, were documented. Statistical analyses examined associations between immune profiles, hematological abnormalities, myelotoxicities, and clinical outcomes. Results. CD8+ T cells increased significantly in neutropenic patients at the end of induction (p=0.028). Reduced Th9 frequencies were observed in patients with thrombocytopenia at diagnosis (p=0.011), while T follicular helper (Tfh) cells decreased in those with infections at the end of induction (p=0.032). CD56dimCD16neg/dim NK cells were elevated in infected patients (p<0.05). Th17 and Th9 subsets co-expressing BTLA, TIGIT, and PD-1 were increased in neutropenic patients, highlighting immune dysregulation. Conclusions. Immune cell profiles, particularly Th9, Tfh, and NK subsets, correlate with hematological abnormalities and complications in children with ALL. These findings underscore the need for further research on immune modulation as a potential strategy to improve outcomes in LMIC contexts.

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