Abstract
T-cell Acute Lymphoblastic Leukemia (T-ALL) is a subtype of acute lymphoblastic leukemia characterized by the proliferation of abnormal T-cell precursors. Nelarabine, a purine analog, has been approved as a targeted therapy for patients with refractory or relapsed T-ALL. This study aims to evaluate the efficacy and safety of Nelarabine, either as monotherapy or in combination with other therapies, in treating T-ALL. A systematic review and meta-analysis were conducted following PRISMA guidelines. We searched Cochrane CENTRAL, PubMed, and Google Scholar up to August 2024 for studies evaluating Nelarabine's efficacy and safety in T-ALL patients. The primary outcome was complete response (CR), with secondary outcomes focusing on adverse events (AEs). Data were analyzed using a random effects model, with statistical significance set at p ≤ 0.05. Sixteen studies involving 1,865 patients were included, with 1,345 receiving Nelarabine. The pooled analysis revealed a CR rate of 37.9% (95% CI: 20.5-55.4%, p < 0.001) for Nelarabine monotherapy. Significant adverse events included neutropenia at 29.1% (95% CI: 9.1-49.1%, p < 0.001), thrombocytopenia at 32.4% (95% CI: 14.8-50.0%, p < 0.001), peripheral motor neuropathy at 17.1% (95% CI: 4.2-30.1%, p = 0.001), and peripheral sensory neuropathy at 15.3% (95% CI: 5.8-24.9%, p = 0.003). For combination therapy, infections occurred in 65.0% (95% CI: 27.1-103.0%, p < 0.001) of patients, febrile neutropenia in 48.7% (95% CI: -8.8-106.3%, p < 0.001), peripheral motor neuropathy in 10.5% (95% CI: 7.9-13.0%, p < 0.001), and peripheral sensory neuropathy in 23.1% (95% CI: 10.6-35.7%, p < 0.001). Nelarabine shows significant efficacy in treating refractory or relapsed T-ALL, with notable CR rates. However, its use, both as monotherapy and in combination therapy, is associated with considerable adverse events, particularly neurotoxicity and hematologic toxicities, necessitating careful monitoring. Further research is needed to optimize its application across diverse patient populations and to better manage its associated toxicities.