nelarabine and Spinal-Cord-Diseases

Nelarabine is one of the newer and novel drugs approved by the USA Food and Drug Administration for treatment of relapsed and resistant acute lymphoblastic leukemia. Although there are a few accounts of the neurologic toxicity of nelarabine in the oncological literature, it has never been discussed from a radiologic stand point to our knowledge. We describe a case of nelarabine-induced myelopathy and review the existing literature in an attempt to characterize the MRI features helpful in making an early diagnosis of this elusive entity.

Topics: Adult; Antineoplastic Agents; Arabinonucleosides; Female; Humans; Magnetic Resonance Imaging; Neuroimaging; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Spinal Cord Diseases; United States

Nelarabine is an effective treatment for T-cell acute lymphoblastic leukemia/lymphoma. Myelopathy is a rare but serious adverse event associated with this drug. Three patients who received nelarabine at the National Cancer Center Hospital from December 2014 to March 2021 developed myelopathy 20 days before, 12 days after, and 29 days after allogeneic hematopoietic cell transplantation (allo-HCT), respectively. Magnetic resonance imaging showed that two of the patients had lesions in the dorsal column or medulla oblongata, and one had no abnormalities in the head or spine. Despite treatment with intravenous immunoglobulin and methylprednisolone, all patients became unable to walk. One patient died on day 101 after allo-HCT due to progressive neurotoxicity. The other two patients showed spontaneous improvement in neurological symptoms, but one died of mucormycosis on day 476. Autopsy revealed spongiosis in the posterior funiculus in both patients who died, and also in the medulla oblongata in one patient. In the surviving patient, positron emission tomography on day 84 showed abnormal accumulation, suggesting continued inflammation. These cases demonstrated pathophysiological features of nelarabine-induced myelopathy and indicate that allo-HCT may worsen the condition. It is necessary to elucidate the underlying mechanism and establish diagnostic methods and therapies.

Topics: Arabinonucleosides; Hematopoietic Stem Cell Transplantation; Humans; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Spinal Cord Diseases

Nelarabine is a nucleoside analog critical for the treatment of patients with T-cell acute lymphoblastic leukemia/lymphoma. However, clinical peripheral and central neurologic adverse events associated with nelarabine administration have been reported. Neuroimaging of brain neurotoxicity has only been described in very few reports in pediatric patients so far. Six children with diagnosed T-cell acute lymphoblastic leukemia who clinically experienced possible, probable, or definite nelarabine-induced toxicity and underwent spine and/or brain MR imaging were reviewed. Neuroimaging findings showed a mixture of patterns including features of acute toxic leukoencephalopathy (seen in 6 cases), posterior reversible encephalopathy syndrome (2 cases), involvement of deep gray structures (1 case) and brainstem (2 cases), cranial and spinal neuropathy (2 cases each), and myelopathy (2 cases). Even though neuroimaging findings are nonspecific, the goal of this article was to alert the pediatric neuroradiologists, radiologists, and clinicians about the possibility of nelarabine-induced neurotoxicity and its broad neuroimaging spectrum.

Topics: Arabinonucleosides; Child; Humans; Posterior Leukoencephalopathy Syndrome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Spinal Cord Diseases

Topics: Arabinonucleosides; Humans; Injections, Spinal; Methotrexate; Spinal Cord Diseases

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.. 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.. Rehabilitation and pharmacological treatments were initiated early, but no evidence of a significant clinical change was obtained.. 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.

Topics: Adult; Arabinonucleosides; Female; Humans; Neurotoxicity Syndromes; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Spinal Cord Diseases

Topics: Antineoplastic Agents; Arabinonucleosides; Child; Fecal Incontinence; Female; Humans; Paraplegia; Peripheral Nervous System Diseases; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Spinal Cord Diseases; Thoracic Vertebrae

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Arabinonucleosides; Combined Modality Therapy; Humans; Magnetic Resonance Imaging; Male; Neurotoxicity Syndromes; Peripheral Nervous System Diseases; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Spinal Cord; Spinal Cord Diseases; Treatment Outcome

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Arabinonucleosides; Disease Progression; Fatal Outcome; Humans; Injections, Spinal; Male; Mediastinal Neoplasms; Mercaptopurine; Methotrexate; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Quadriplegia; Spinal Cord; Spinal Cord Diseases