Efficacy of Melatonin for the Treatment of Moderate to Severe Vincristine-Induced Neuropathy in in Children with Acute Lymphoblastic Leukemia: A Randomized Controlled Trial

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, accounting for 26% of pediatric blood malignancies. Vincristine is a widely used chemotherapy agent for ALL, but vincristine-induced peripheral neuropathy (VIPN) is the most prevalent and significant side effect associated with its administration. Objectives: This study aims to evaluate the efficacy of melatonin in treating VIPN in children with ALL. Methods: This randomized controlled trial included children aged 5 to 12 years with ALL who were clinically diagnosed with VIPN using the pediatric-modified total neuropathy score. Patients were randomly assigned to either a control or treatment group. The vincristine dose for each of the four treatment phases (induction, consolidation, maintenance, and intensification) was 1.5 mg/m², administered intravenously. Baseline and one-month post-treatment measurements included the CTCAE score (to assess VIPN), PedsQL child and parent scores (to evaluate quality of life), and pediatrics-modified total neuropathy (PEDs MTNs) scores. Patients received either 3 - 5 mg of melatonin or a placebo daily for one month. Results: A total of 20 patients (mean age: 7.45 ± 2.31; 55% female) were included, with 60% allocated to the treatment group. Baseline clinical and demographic data showed no significant differences between groups. The study found that melatonin administration at a dose of 3 mg daily for one month did not significantly improve VIPN in children with ALL. However, a significant difference was observed in pain scores after the intervention, with children in the placebo group reporting a significantly higher mean pain score compared to the treatment group (4 ± 2.39 vs. 2 ± 2.26, P = 0.041). Melatonin had a substantial and statistically significant impact on the quality of life of the children and their parents, as well as on the children’s pain scores. Conclusions: Although the CTCAE score was reduced, no significant difference was observed between the melatonin and placebo groups. However, melatonin demonstrated a positive effect on health-related quality of life and pain reduction in children with ALL diagnosed with VIPN.