Toxic Rapidly Progressive Myelopathy Induced by Nelarabine in an Adolescent with Relapsed Pre-T-ALL

Background: The purine analogue Nelarabine has been used as a chemotherapeutic agent to treat refractory acute T-lymphoblastic leukemia (T-ALL) since 2007. Neurotoxic adverse drug reactions (ADR), mostly manifesting as polyneuropathy, are well known. In addition, individual cases of myelopathy with flaccid paralysis or even paraplegia have been reported. These symptoms are suggested to be a result of potentia toxic effects on mitochondrial metabolism. We report the rapid progression of a myelopathy caused by Nelarabine in an adolescent with relapsed pre-T-ALL.

Case Report: A 14-year-old adolescent presented for neuropediatric clarification of a distal polyneuropathy after previous intensive oncological treatment including second allogeneic stem cell transplantation and a recent Nelarabine-containing chemotherapy cycle. Three weeks after treatment was completed, the boy presented with distal paresthesia and beginning distal paresis. Within a few days, these symptoms were followed by flaccid paralysis and neurogenic bladder dysfunction. Quadriplegia, oropharyngeal dysphagia, and respiratory insufficiency requiring invasive ventilation occurred upon further progress within 6 weeks.

Diagnostics: Spinal MRI in T2w demonstrated a pathological increase of signal intensity almost within the completely spinal cord, primarily affecting the dorsal and lateral column as a sign of medullary edema. No indications for metabolic, infectious, or malign causes were found in comprehensive biochemical diagnostic testing. 7S-IVIG and steroids did not provide any therapeutic effect.

Conclusion: The rapid progression of a toxic myelopathy induced by Nelarabine represents a severe ADR. Characteristic spinal MRI findings with initially isolated affection of the dorsal and lateral column could point the way toward this diagnosis.