Shakeel Laiba, Khaliq Nawal, Shaukat Ayesha, Khan Afsheen, Riaz Rumaisa, Batool Um E Abiha, Zia Muhammad Twaha, Akilimali Aymar
Internal Medicine, Dow University of Health Sciences (DUHS), Karachi, Pakistan.
Department of Research, Medical Research Circle, Goma, 73 Gisenyi, Democratic Republic of the Congo.
Ann Hematol. 2025 Feb;104(2):1139-1155. doi: 10.1007/s00277-024-06121-z. Epub 2025 Jan 10.
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.
T细胞急性淋巴细胞白血病（T-ALL）是急性淋巴细胞白血病的一种亚型，其特征是异常T细胞前体的增殖。奈拉滨，一种嘌呤类似物，已被批准作为难治性或复发性T-ALL患者的靶向治疗药物。本研究旨在评估奈拉滨单药治疗或与其他疗法联合治疗T-ALL的疗效和安全性。按照PRISMA指南进行了系统评价和荟萃分析。我们检索了截至2024年8月的Cochrane CENTRAL、PubMed和谷歌学术，以查找评估奈拉滨在T-ALL患者中的疗效和安全性的研究。主要结局是完全缓解（CR），次要结局集中在不良事件（AE）。使用随机效应模型分析数据，设定统计学显著性为p≤0.05。纳入了16项涉及1865例患者的研究，其中1345例接受了奈拉滨治疗。汇总分析显示，奈拉滨单药治疗的CR率为37.9%（95%CI：20.5-55.4%，p<0.001）。显著不良事件包括中性粒细胞减少，发生率为29.1%（95%CI：9.1-49.1%，p<0.001）；血小板减少，发生率为32.4%（95%CI：14.8-50.0%，p<0.001）；周围运动神经病变，发生率为17.1%（95%CI：4.2-30.1%，p=0.001）；周围感觉神经病变，发生率为15.3%（95%CI：5.8-24.9%，p=0.003）。对于联合治疗，65.0%（95%CI：27.1-103.0%，p<0.001）的患者发生感染，48.7%（95%CI：-8.8-106.3%，p<0.001）的患者发生发热性中性粒细胞减少，10.5%（95%CI：7.9-13.0%，p<0.001）的患者发生周围运动神经病变，23.1%（95%CI：10.6-35.7%，p<0.001）的患者发生周围感觉神经病变。奈拉滨在治疗难治性或复发性T-ALL方面显示出显著疗效，CR率显著。然而，其单药治疗和联合治疗均与相当多的不良事件相关，特别是神经毒性和血液学毒性，需要仔细监测。需要进一步研究以优化其在不同患者群体中的应用，并更好地管理其相关毒性。
