Central nervous system neurotoxicity associated with nelarabine in T-cell acute lymphoblastic leukemia

Abstract

Introduction Nelarabine, a prodrug of arabinosylguanine has lineage-specific toxicity for T lymphoblasts and is used to treat refractory or relapsed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma patients. The most commonly observed adverse effects associated with nelarabine are mainly hematological, i.e. neutropenia, anemia, and thrombocytopenia. Additionally, neurological, and gastrointestinal toxicities have been reported. Central nervous system neurotoxicity associated with nelarabine is very rare. Case description A 37-year-old man patient diagnosed with T-cell acute lymphoblastic leukemia had experienced generalized tonic-clonic seizure which lasted for a few seconds and upper extremity weakness after three weeks of the nelarabine infusion. Computed tomography and magnetic resonance imaging have shown periventricular and nucleus caudatus abnormalities. Radiological findings suggested toxic leukoencephalopathy and acute infarct of right nucleus caudatus. Management and outcome After high-dose steroids, intravenous immunoglobulin, and support treatment, his neurologic symptoms disappeared except for mild peroral numbness. However, radiological sequelae persisted despite clinical improvement. Conclusion Physicians involved in the care of these patients who use nelarabine should be aware of the fact that cerebral toxicity of the nelarabine may occur especially in the presence of predisposing factors. It is crucial to monitor closely those patients receiving nelarabine and also those who have additional predisposing factors for neurotoxicity.

Management of Nelarabine induced neurotoxicity in a child with T-cell acute lymphoblastic lymphoma

“…Pehlivan et.al was to our knowledge the first to demonstrate the improvement of symptoms following treatment. 7 The combination of steroids, intravenous immunoglobulin and aminophylline worked for the presented patient, but larger numbers are needed to validate this as an approved treatment regimen.…”

“…[4][5][6] Pehlivan et al have demonstrated successful management of the neurotoxicity of Nelarabine in their article, "Central Nervous System Toxicity associated with Nelarabine in T-Cell Acute Lymphoblastic Leukemia.". 7 We also encountered a similar case and would like to share our experience. Informed consent or permission to publish the case report was obtained from the family.…”

“…Given the reported poor outcomes of Nelarabine neurotoxicity, aminophylline was also added as per published literature supporting its role in methotrexate-induced neurotoxicity. 7,9 It was felt that it was unlikely to cause any harm and may be beneficial. Clinical improvement was noticed within 72 hours of the initiation of therapy, with complete resolution of symptoms barring swallowing difficulty by day 5.…”