N-acetylcysteine vs placebo as adjunctive treatment in paediatric leukaemia: A single blind, randomized controlled trial

Abstract

Background: Acute lymphoblastic leukaemia (ALL) accounts for about 25% of all cancer types in children. Many chemotherapeutic agents have been shown to be related to increased oxidative stress and hepatotoxicity which affect the survival rate. N-acetylcysteine (NAC) has been used as adjunctive treatment in malignancy. Objectives: To analyse the effect of NAC administration towards blood oxidant, transaminase enzyme, and bilirubin level in ALL children undergoing induction phase of chemotherapy. Method: This is a single-blind placebo-controlled randomized clinical trial carried out from August to December 2020 in Cipto Mangunkusumo National Hospital, Jakarta, Indonesia. Subjects were randomized consecutively into 2 groups treated with NAC or placebo. Inclusion criteria were newly diagnosed ALL-standard risk (SR) children undergoing chemotherapy induction. Exclusion criteria were subjects contraindicated to NAC, already diagnosed with liver dysfunction, and already taken antioxidants. Data were analysed using SPSS 21. Normality test was conducted followed by data analysis with unpaired t-test. Results: A total of 18 subjects were included in study and 2 of them were excluded. Malondialdehyde levels showed an increase of 0.17nmoL in the NAC group and a decrease of 0.19nmoL in the placebo group. Aspartate transaminase (AST) level increased in mean of 11.40 U/L in the NAC group compared to placebo group 5.67 U/L. Alanine transaminase (ALT) level in the NAC group showed an increase in mean of 23.24 U/L compared to placebo group which showed a decrease in mean of 3.5 U/L. Bilirubin level in the NAC group showed an increase of 0.7 mg/dL compared to placebo group 0.17 mg/dL. There was no significant difference in MDA levels, AST, ALT, and bilirubin levels in the 2 groups (p=0. 186; p=0.638; p=0.164; p=0.352, respectively). Conclusions: Higher malondialdehyde level was shown as a trend in subjects in both groups before chemotherapy was done. N-acetyl cysteine administration showed no significant difference in reducing MDA levels, transaminase enzymes, and bilirubin levels in ALL-SR patients compared to placebo.