Nelarabine-Induced Neurotoxicity: Reversible Damage not only on Peripheral Nerves

Nelarabine has a T-cell-specific action; neurotoxicity is an important dose-limiting toxicity. Rare, dramatic cases of peripheral neurotoxicity have been reported, also with features similar to Guillain-Barré syndrome (GBS). A 28-year-old man affected by T cell acute lymphoblastic leukaemia/lymphoma developed a severe neurotoxicity, after having being treated with nelarabine, obtaining a complete remission for a mediastinal relapse without bone marrow involvement. One month after treatment, he developed hypoesthesia in lower limbs and progressive gait imbalance: he was admitted to the Haematology ward. Haematologists decided to administer intravenous Immunoglobulin (IVIG), 0.4 mg/Kg per 5 days, in the hypothesis of a GBS. However, the clinical picture was not completely consistent with this hypothesis. There was mild bilateral inferior limb weakness, hypoesthesia with a L2-L3 sensory level bilaterally, increased deep tendon reflexes in lower limbs. Romberg’s signs was positive and gait imbalance worsened at eye closure. He underwent cerebrospinal fluid examination (mild hyperproteinorrachia, 52 mg/dL) with negative microbiological and virological tests. A nerve conduction study (NCS) was normal, except for mild conduction velocity reduction in the common peroneal nerve. Routine blood testing and onconeural antibodies were normal or negative. Gadolinium-enhanced brain and spinal cord MRI were normal. After IVIG administration the symptoms worsened. A neurological consult was obtained. Inability to stand, walk unattended for a severe sensory ataxia, and bladder dysfunction were observed. A subsequent MRI showed an altered pattern in the dorsal columns from the cervical to the dorsal spinal cord. Somatosensory evoked potentials (SSEP) revealed intraspinal sensory ascending pathways damage. NCS now evidenced a peripheral, mainly motor, involvement with diminished conduction velocities, augmented distal latencies and augmented F waves in lower limb nerves; these findings were stable during subsequent NCS monitoring. A bone marrow biopsy and positron emission tomography (PET) excluded a relapse. The neurological disturbance was then regarded as iatrogenic so no other specific treatment for neurological symptoms than long-term physiotherapy was performed and immunotherapy with donor lymphocytes infusion (DLI) was allowed, to maintain the oncological remission status. One year after the patient was asymptomatic and in complete remission. Only minor alterations were still present on MRI and SSEP. Nelarabine neurotoxicity can cause a severe neuropathy/myelopathy, still potentially reversible, provided prolonged physiotherapy, since no medical treatment is available. Thus, for nelarabine-treated patients, neurological monitoring should be suggested. DLI was performed without any worsening of neurological outcome, different from what was previously reported