Clinico-radiological profile, management and follow-up of methotrexate induced neurotoxicity in children with acute lymphoblastic leukemia

Abstract

Methotrexate-induced neurotoxicity is a well-defined side-effect of high-dose and intrathecal methotrexate with characteristic clinico-radiological findings and transient nature. Our experience in managing this entity in children with acute lymphoblastic leukemia(ALL) is reported here. All children with de novo ALLregistered from January 2016 through December 2021 who developed methotrexate-induced neurotoxicity were included. Of children with ALL treated during the study period, thirty-three experienced methotrexate induced neurotoxicity with an incidence of 1.25%. Stroke-like symptoms(36.36%; 12/33) were the most common clinical manifestation followed by seizures(30.3%, 10/33). Twenty-three patients had radiological features consistent with methotrexate-induced leukoencephalopathy. With emerging evidence, thirty-one patients were re-challenged with methotrexate (IV/IT), of whom 4 patients had recurrence of symptoms. No long-term neurological sequalae were noted in our cohort, despite rechallenging. Therefore in our study, methotrexate induced neurotoxicity is a self-limiting toxicity and methotrexate can be re-challenged safely without compromising theintensity of CNS-directed therapy.

Keywords:

• Methotrexate
• neurotoxicity
• leukoencephalopathy
• leukemia
• child

Acknowledgements

PediatricHemato-lymphoid disease management group at the Tata Memorial Hospital, Mumbai

Disclosure statement

No potential conflict of interest was reported by the author(s).

Table 1. Clinical characteristics of patients with methotrexate induced neurotoxicity in de novo ALL(N = 33).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.