Vincristine-Induced Neurotoxicity in Acute Lymphoblastic Leukemia: A Comprehensive Systematic Review

Acute lymphoblastic leukemia (ALL) is one of the most common pediatric malignancies, with vincristine (VCR) being a key chemotherapeutic agent in its treatment. The present review aims to assess the risk factors, clinical manifestations, and management strategies of VCR-induced neurotoxicity in patients with ALL. A systematic search of the literature was performed using PubMed, Scopus, and CINAHL Ultimate. Inclusion criteria encompassed studies involving ALL patients treated with VCR, reporting neurotoxicity outcomes. The study was conducted following the PRISMA guidelines. From 4310 articles screened, 109 studies met the inclusion criteria. Neurotoxicity was predominantly characterized by peripheral neuropathy, cranial nerve involvement, and autonomic dysfunction. The severity of neurotoxicity was associated with cumulative vincristine exposure, with doses exceeding 25 mg/m² frequently linked to severe neuropathy. Age was a key factor, with older children and adolescents showing greater susceptibility. Genetic polymorphisms, particularly CEP72 rs924607 TT and ABCB1 variants, were identified as significant risk factors. Concurrent methotrexate use was found to exacerbate VCR-induced neurotoxicity. Sensory disturbances, motor impairment, and gastrointestinal autonomic dysfunction, including constipation and ileus, were among the most frequently reported symptoms. Management strategies primarily involved dose adjustments, drug discontinuation, and symptomatic treatments, including pyridoxine and pyridostigmine, though their efficacy remained inconsistent. Emerging strategies such as altered infusion methods showed promise in reducing toxicity severity. VCR-induced neurotoxicity remains a significant challenge in ALL therapy. Standardized neurotoxicity assessment tools and prospective studies are needed to improve early detection and optimize management strategies, ultimately balancing treatment efficacy with minimizing neurological morbidity.