Toxicity profile of high-dose methotrexate in young children with central nervous system tumors

Ashley N Chavana; Zachary L Taylor; Nicholas DeGroote; Holly B Lindsay; Hannah E Sauer; Emily J Mason; Eric S Schafer; Tamara P Miller; Sharon M Castellino; Lauren Pommert; Maureen M O'Brien; Laura B Ramsey; M Brooke Bernhardt; Austin L Brown

doi:10.1002/pbc.31213

Toxicity profile of high-dose methotrexate in young children with central nervous system tumors

Pediatr Blood Cancer. 2024 Oct;71(10):e31213. doi: 10.1002/pbc.31213. Epub 2024 Jul 22.

Authors

Ashley N Chavana¹, Zachary L Taylor^{2

3

4}, Nicholas DeGroote^{5

6}, Holly B Lindsay^{7

8}, Hannah E Sauer^{1

9}, Emily J Mason¹, Eric S Schafer^{1

9}, Tamara P Miller^{5

6}, Sharon M Castellino^{5

6}, Lauren Pommert^{3

4}, Maureen M O'Brien^{3

4}, Laura B Ramsey^{10

11}, M Brooke Bernhardt¹², Austin L Brown^{1

9}

Affiliations

¹ Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
² Division of Translational and Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
³ Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁴ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
⁵ Division of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
⁶ Aflac Cancer & Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
⁷ Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, Colorado, USA.
⁸ Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
⁹ Texas Children's Cancer and Hematology Center, Texas Children's Hospital, Houston, Texas, USA.
¹⁰ Division of Clinical Pharmacology, Toxicology & Therapeutic Innovation, Children's Mercy Kansas City, Kansas City, Missouri, USA.
¹¹ Department of Pediatrics, School of Medicine, University of Missouri Kansas City, Kansas City, Missouri, USA.
¹² Department of Pharmacy and Pharmaceutical Science, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

PMID: 39039774
DOI: 10.1002/pbc.31213

Abstract

High-dose methotrexate (HD-MTX) is used in the treatment of children with central nervous system (CNS) tumors; however, toxicity information is limited. We characterized toxicities following 102 administrations of HD-MTX (4.6-13.5 g/m²) infused over 4 or 24 h in 38 children with a CNS tumor before 6 years of age (2010-2020). Delayed clearance of methotrexate occurred following 24% of infusions. Common Terminology Criteria for Adverse Events v5 grade 2-3 mucositis was observed in 47% of individuals, Grade 4 neutropenia in 76%, and grade 3-4 thrombocytopenia in 58%. No neurotoxicity was observed. HD-MTX can be safely used with supportive care and monitoring.

Keywords: CNS tumors; children; methotrexate; toxicity.

MeSH terms

Antimetabolites, Antineoplastic* / administration & dosage
Antimetabolites, Antineoplastic* / adverse effects
Central Nervous System Neoplasms* / drug therapy
Child
Child, Preschool
Female
Follow-Up Studies
Humans
Infant
Male
Methotrexate* / administration & dosage
Methotrexate* / adverse effects
Mucositis / chemically induced
Neutropenia / chemically induced
Prognosis
Retrospective Studies

Substances

Methotrexate
Antimetabolites, Antineoplastic