ABSTRACT
Acute lymphoblastic leukemia (ALL), the most common hematologic malignancy in children, also occurs in adults and is characterized by uncontrolled proliferation of immature lymphoid cells. Chemotherapy, while improving survival, generates high levels of reactive oxygen species (ROS), causing oxidative stress that can damage lipids, proteins, and DNA, potentially affecting treatment response, toxicity, and outcomes. Evaluating oxidant and antioxidant status in ALL patients is therefore essential.
This study included a total of 64 individuals: 21 newly diagnosed ALL (ND-ALL) patients (median age 10 years, interquartile range (IQR) 3–27.5), 23 patients on maintenance chemotherapy (median age 13 years, IQR 5–23), and 20 healthy controls (median age 11.5 years, IQR 5–23) in a cross-sectional study. ND-ALL patients were also reassessed following remission induction (RI) therapy in a longitudinal study. Oxidative stress markers, including malondialdehyde (MDA), 8-hydroxy-2’-deoxyguanosine (8-OHdG), and protein carbonyl (PC), along with antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC), were measured using enzyme-linked immunosorbent assay (ELISA), while complete blood count (CBC) and biochemical tests like alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total serum bilirubin (TSB), lactate dehydrogenase (LDH), uric acid, creatinine, and urea were analyzed to assess hematopoietic and organ functions.
Data were analyzed using GraphPad Prism 9.0.0 with appropriate parametric or non-parametric tests, Receiver Operating Characteristic (ROC) curve analysis was performed using MedCalc Statistical Software version 18.11.3, and significance was set at p ≤ 0.05.
In the cross-sectional study, MDA p-value ≤ 0.05 and 8-OHdG p-value 0.001 were significantly higher in ND-ALL patients. SOD demonstrated a considerable decline p-value ≤0.001, the antioxidants GSH-Px and T-AOC also decreased significantly p-value ≤ 0.01. There were no significant differences between the maintenance group and the controls. Significant increases in MDA, 8-OHdG, and PC (p≤ 0.05, 0.01, 0.01, respectively), and decreases in GSH-Px, SOD, and T-AOC (p ≤ 0.01, 0.05, 0.01, respectively) were observed following treatment. Among oxidative stress biomarkers, 8-OHdG (>370.43 pg/mL) showed the highest sensitivity (95.24%) for distinguishing ND-ALL from RI groups, while SOD (≤2.47 ng/mL) demonstrated good diagnostic performance with 80.95% sensitivity and 66.67% specificity p-value 0.05. White blood cell (WBC) and lymphocytes were elevated in ND-ALL, whereas red blood cell (RBC), hemoglobin (Hb), hematocrit (HCT), platelet (Plt), and granulocytes decreased with a p-value 0.001; following remission induction (RI) chemotherapy, WBC and lymphocytes decreased with a p-value 0.001, Plt increased with a p-value ≤ 0.001, minimal residual disease (MRD) analysis using 8-color flow cytometry (BD Biosciences) showed that 86% of patients achieved complete remission, 9% achieved partial remission, and 5% achieved no remission. Biochemically, AST and ALT increased with a p-value ≤ 0.001 after chemotherapy, while LDH decreased p-value 0.001.
Chemotherapy significantly alters the oxidant–antioxidant balance and hematological and biochemical parameters in ALL. Therefore, monitoring oxidative stress and MRD, along with hematological and biochemical parameters, are important to evaluate the impact of these parameters on treatment response and to help optimize therapy outcomes.
