Nelarabine (Arranon) for ALL causes neurotoxicity

Nelarabine is a nucleoside analog approved by the FDA for treatment of patients with refractory T-cell ALL and T-cell lymphoblastic lymphoma (T-LBL). These diseases are usually treated aggressively with combination chemotherapy (vincristine, prednisone, anthracycline, asparaginase, cyclophosphamide and cytarabine). It is demythylated to ara-G (ara-GTP) which is incorporated into dna, causing apoptosis and fragmentation. 18 % of refractory patients (5/28) has a complete response. Median survival was 20 weeks. Among children, 9/39 (23%) had a CR with median survival of 13 weeks. The most common AE's are anemia, leukopenia, thrombocytopenia, HA, somnolence and GI effects, dyspnea and peripheral neuropathy. Neurotoxicity, which can be fatal, is dose limiting; paresthesia, ataxia, ocnfusion, convulsions, and coma.