Treatment of two cases on the same day of intrathecal methotrexate overdose using cerebrospinal fluid exchange and intrathecal instillation of carboxypeptidase-G2

Pediatr Hematol Oncol. 2018 Aug-Sep;35(5-6):350-354. doi: 10.1080/08880018.2018.1524536. Epub 2019 Jan 23.

Abstract

Background: Two 14-year old boys with acute lymphocytic leukemia were treated according to the NOPHO-ALL-08 protocol with intrathecal methotrexate (MTX) on the same day. Due to a preparation error in the hospital pharmacy, they were both given 240 mg of MTX instead of the prescribed 12 mg. Treatment (or methods): Both patients developed acute neurotoxicity with confusion, pain and seizures. Intravenous dexamethasone and folinic acid (leucovorin) was given. Exchange of cerebrospinal fluid was performed. Intrathecal glucarpidase (carboxypeptidase-G2) was administered after 11 h.

Results: One patient developed a toxic arachnoiditis. Three years after the incident, one patient has no neurological or neuropsychological sequelae after the overdose, while the other reports some loss of short-term memory.

Conclusion: Fast recognition and treatment of intrathecal MTX overdose is critical to survival and outcome. Efforts to prevent such overdoses are of vital importance.

Keywords: Intrathecal; carboxypeptidase; chemotherapy; methotrexate; overdose; pediatric.

Publication types

  • Case Reports

MeSH terms

  • Acute Kidney Injury* / cerebrospinal fluid
  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / therapy
  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cerebrospinal Fluid
  • Drug Overdose / cerebrospinal fluid
  • Drug Overdose / therapy*
  • Humans
  • Injections, Spinal
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / cerebrospinal fluid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • gamma-Glutamyl Hydrolase / administration & dosage*

Substances

  • gamma-Glutamyl Hydrolase
  • Methotrexate