Severe, Fatal Methotrexate-related Neurotoxicity in 2 Adolescent Patients With ALL

J Pediatr Hematol Oncol. 2020 Nov;42(8):e839-e844. doi: 10.1097/MPH.0000000000001706.


Neurotoxicity is a well-documented adverse effect of methotrexate in the treatment of pediatric cancers. The spectrum of symptoms is broad, can include stroke-like episodes and seizures, and classically resolves within days. The majority of patients tolerate subsequent doses without recurrence of symptoms. The population of patients who experience persistent and irreversible neurologic symptoms is poorly described, with the existing literature suggestive of a relationship with radiation therapy. The authors present a case series of 2 patients with pre-B-cell acute lymphoblastic leukemia who developed severe and ultimately fatal methotrexate-related neurotoxicity in the absence of radiation.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Antimetabolites, Antineoplastic / adverse effects*
  • Fatal Outcome
  • Female
  • Humans
  • Methotrexate / adverse effects*
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Retrospective Studies
  • Severity of Illness Index*
  • Young Adult


  • Antimetabolites, Antineoplastic
  • Methotrexate