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 the vitamin D receptor is expressed in the mucosa and that a relation exists between low vitamin D levels and an increased inflammatory mucosal state and impaired mucosal tissue barriers. We examined the prevalence of vitamin D deficiency and the change in vitamin D levels in children with ALL during high-dose methotrexate (HD-MTX) treatment and studied the association between vitamin D levels and MTX-induced oral mucositis.


We assessed 25(OH)D2, 25(OH)D3 and 24,25(OH)2D3 levels in 99 children with ALL before start of 4x 5g/m2 HD-MTX (T0) and in 81/99 children after discontinuation of HD-MTX (T1). Two cut-off values for Vitamin D deficiency exist: 25(OH)D3 levels <30 nmol/L and <50 nmol/L. Oral mucositis was defined as grade ≥ 3 according to the National Cancer Institute Criteria.


Vitamin D deficiency occurred in respectively 8% (<30 nmol/L) and 33% (<50 nmol/L) of patients at T0, and more frequently in children >4 years of age as compared to children between 1-4 years of age. A decrease in 25(OH)D3 levels during HD-MTX therapy was associated with the development of 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 oral mucositis.


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 associated with a higher chance of developing oral mucositis in children with ALL.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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