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We describe a case of a massive acute leukoencephalopathy after only one TIT, in a 5 year-old child with an early isolated CNS relapse of ALL (26 months after the first diagnosis), rapidly proceeding to comatose status.

At admission for disease restaging at the end of first-line trial, the child showed physical and neurological examination completely negative, such as haematological, bioumoral and ultrasound findings. The cerebrospinal fluid (CSF) appeared turbid and liquoral pressure increased. CSF count showed 8100 cells/µl; morphology and flow citometry confirmed an early isolated CNS relapse. Due to the abnormal pleocytosis, TIT administration associated with oral dexamethasone was suddenly performed without any other concomitant chemotherapy. To prevent acute toxicities from tumor lysis syndrome, the patient received hydratation, allopurinol, acetazolamide and prophylaxis of seizures with levetiracetam. After few hours from TIT, the child developed severe headache followed by skin urticarial rash, high blood pressure and hallucinations, rapidly evolving in flaccid paralysis of lower extremities. A brain resonance (MRI) showed diffuse areas of hyperintensity of white matter, particularly cortical and subcortical areas, cerebellar region, optic chiasm and brainstem in T2-Flair sequences; spinal cord shower massive edema, especially in lombar region. The MRI pattern was interpreted as diffuse grade IV leukoencephalopathy of probable toxic nature. The child, 30 h after TIT, was transferred to intensive care unit for progressive ascending paralysis and respiratory distress that required intubation. During the following days, other three diagnostic lumbar puncture were performed that showed significant reduction of blasts cells (20, 10 and 0 cells /µL, respectively).

Although leukoencephalopathy following IT MTX or ARA-C administration are described, the severity and rapidity of event’s onset, associated with CSF remission after a single TIT administration, suggests us that neurotoxicity could be related to massive blast cytolysis with subsequent cytokine release syndrome causing an inflammatory leukoencephalopathy. This syndrome is a frequent complication of blinatumomab or chimeric antigen receptor T-cells administrations. The CSF IL-6 dosing could clarify the pathogenesis of the event.