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

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.