A decrease in vitamin D levels is associated with methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia

N Oosterom, N F Dirks, S G Heil, R de Jonge, W J E Tissing, R Pieters, M M van den Heuvel-Eibrink, A C Heijboer, S M F Pluijm

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


PURPOSE: Children with acute lymphoblastic leukemia (ALL) are at increased risk of vitamin D deficiency, which might make them more susceptible to developing adverse events. Previous studies showed that low vitamin D levels were associated with an increased inflammatory mucosal state and impaired mucosal tissue barriers. We examined the prevalence of vitamin D deficiency and studied the association between vitamin D levels and methotrexate (MTX)-induced oral mucositis in pediatric ALL.

METHODS: We assessed 25-hydroxyvitamin D (25(OH)D3) and 24,25-dihydroxyvitamin D (24,25(OH)2D3) levels in 99 children with ALL before the start of 4 × 5 g/m2 high-dose methotrexate (HD-MTX) (T0) and in 81/99 children after discontinuation of HD-MTX (T1). Two cutoff values for vitamin D deficiency exist: 25(OH)D3 levels < 30 and < 50 nmol/L. Oral mucositis was defined as grade ≥ 3 according to the National Cancer Institute Criteria.

RESULTS: Vitamin D deficiency occurred in respectively 8% (< 30 nmol/L) and 33% (< 50 nmol/L) of the patients at T0, and more frequently in children > 4 years of age as compared to children between 1 and 4 years of age. A decrease in 25(OH)D3 levels during HD-MTX therapy was associated with developing severe oral mucositis (OR 1.6; 95% CI [1.1-2.4]). 25(OH)D3 and 24,25(OH)2D3 levels at T0 and the change in 24,25(OH)2D3 levels during therapy were not associated with the development of severe oral mucositis.

CONCLUSIONS: This study showed that vitamin D deficiency occurs frequently in pediatric ALL patients above the age of 4 years. A decrease in 25(OH)D3 levels during MTX therapy was observed in children with ALL that developed severe oral mucositis.

Original languageEnglish
Pages (from-to)183-190
Number of pages8
JournalSupportive Care in Cancer
Issue number1
Publication statusPublished - Jan 2019


  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Child
  • Child, Preschool
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant
  • Male
  • Methotrexate/administration & dosage
  • Netherlands/epidemiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood
  • Prevalence
  • Stomatitis/blood
  • Vitamin D/blood
  • Vitamin D Deficiency/blood
  • Withholding Treatment
  • Young Adult


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