Nelarabine-associated myelopathy in a patient with acute lymphoblastic leukaemia: Case report

Abstract

Introduction Nelarabine is a purine analogue approved for the treatment of patients with T-cell lymphoblastic lymphoma and T-cell acute lymphoblastic leukaemia (T-ALL) that have relapsed or are refractory to two previous chemotherapy regimens. Adverse reactions to nelarabine include neurological toxicity, the pathophysiological mechanisms of which are unknown, although the administration of intrathecal therapy at therapeutic doses given concomitantly with high-dose systemic chemotherapy that crosses the blood–brain barrier may potentiate neurotoxicity. Case report We report a case of a 29-year-old woman with a diagnosis of relapsed T-ALL who developed severe myelopathy and polyneuropathy of toxic origin that led to paraplegia, upper-limb paresis, and dysautonomia after the first cycle of nelarabine. Management and outcome Rehabilitation and pharmacological treatments were initiated early, but no evidence of a significant clinical change was obtained. Discussion Neurotoxicity is a dose-dependent side effect of nelarabine. It is therefore important to consider previously administered neurotoxic drugs before using nelarabine and to monitor patients closely so as to be able to act promptly in case of toxicity. In accordance with the data obtained and based on the Naranjo algorithm, the adverse reaction could be considered possible.

A phase 1 study to evaluate the safety, pharmacology, and feasibility of continuous infusion nelarabine in patients with relapsed and/or refractory lymphoid malignancies

“…In previous reports by other groups, nelarabine led to clinically significant rates of seizures (5%–10%) when used as short duration infusions, 33,34 although some studies in adults have now shown lower rates of similar adverse events 4 . Anecdotal but important case reports of nelarabine‐induced irreversibly myelopathy have been reported, which can significantly limit its use 35–37 . However, in our study, with the use of continuous infusion of nelarabine, we did not encounter any central neurotoxicity unexplainable by CNS leukemic involvement, and this is a reassuring signal that should be confirmed in further studies.…”

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

“…12 Nelarabine is approved in 2005 for the treatment of patients with relapsed and refractory T-LBL and T-ALL. 10 Nelarabine generally causes both central and peripheral neurotoxicities dose-dependently which are self-limited. However, more serious (grade 3 or 4) neurotoxicities such as demyelination, spinal cord necrosis, GBS, and polyradiculoneuropathies are reported predominantly in the pediatric population.…”

“…However, more serious neurological adverse effects including necrosis of the spinal cord, demyelination, Guillain-Barre syndrome (GBS), and polyradiculoneuropathy have also been described. [3][4][5][6][7][8][9][10] Potentiation of neurological toxicity of nelarabine might likely be observed with the concomitant use of other neurotoxic agents such as high-dose or intrathecal methotrexate (MTX) or prior cranial radiotherapy. 8,10,11 Here, we report toxic leukoencephalopathy (TL) due to myelination damage; basal ganglia infarction due to secondary CNS vasculitis, or the predisposition to thrombogenicity in a male patient with T-ALL as a complication of nelarabine treatment.…”

Dorsal myelopathy after nelarabine and intrathecal methotrexate therapy

“…Timing of the neurological symptoms, distribution of the spinal lesions, and the dose of NEL overlapped between patients with good and poor outcomes. Plasma exchange, high‐dose steroids, or intravenous immunoglobulin therapies were not effective in many patients 2 . Kuhlen et al reported that age is associated with neurotoxicity in a multivariate analysis of patients with NEL, and young age can be the factor related to the good outcome in the present patient 1 …”

“…Amer‐Salas et al reviewed 15 patients, including their own case, with myelopathy after treatment with NEL (Table S1). 2 Nine patients had irreversible neurological abnormalities, and three patients experienced neurological recovery 2 . The prognostic factors for myelopathy remain to be clarified.…”