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.
Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, and despite advances in cancer treatment, there are still cases of relapse and death secondary to resistance to chemotherapy or apoptosis. One of the mechanisms is the activation of the IKK/NF-κB signaling pathway that leads to the expression of genes that interfere with apoptosis. Pentoxifylline (PTX) can block phosphorylation of IκB, thus preventing the NF-κB activity, therefore the activation of anti-apoptotic genes. Procedure: Controlled versus placebo, randomized, double-blind clinical trial. Pediatric patients with ALL during induction therapy were assigned either to pentoxifylline or the placebo group. Bone marrow aspirates were performed on day-1, day-8, day-15, and day-22. We performed flow MRD, determination of apoptosis by annexin-V/propidium iodide test, and senescence by β-galactosidase activity. Results: PTX group had higher percentage of apoptotic cells on day-8 (41.3% vs 19.4%, p=0.029), and day-15 (35.0% vs 14.2%, p <0.01). No difference was observed in the senescence determinations. On day-8, the PTX group showed MRD of 0.25% vs 18.2% (p <0.01) in the placebo group; at day-15 the PTX group showed MRD of 0.09% vs 1.4% (p=0.02). Patients with MRD <0.01% at day-8 had 3-year OS of 81.6% vs 58.3% (p=0.03); at day-15 patients with MRD <0.01% at day-8 had 3-year OS of 77.9% vs 54.5% (p=0.03). Conclusion: PTX group showed a MRD <0.01% earlier, on day-8 and 15, and presented a higher percentage of apoptotic cells. In the entire cohort, patients with MRD <0.01% on day 8 or 15 showed better OS.