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

PurposeChildren 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.MethodsWe assessed 25-hydroxyvitamin D (25(OH)D-3) and 24,25-dihydroxyvitamin D (24,25(OH)(2)D-3) levels in 99 children with ALL before the start of 4x5g/m(2) 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)D-3 levels <30 and <50nmol/L. Oral mucositis was defined as grade 3 according to the National Cancer Institute Criteria.ResultsVitamin D deficiency occurred in respectively 8% (<30nmol/L) and 33% (<50nmol/L) of the patients at T0, and more frequently in children >4years of age as compared to children between 1 and 4years of age. A decrease in 25(OH)D-3 levels during HD-MTX therapy was associated with developing severe oral mucositis (OR 1.6; 95% CI [1.1-2.4]). 25(OH)D-3 and 24,25(OH)(2)D-3 levels at T0 and the change in 24,25(OH)(2)D-3 levels during therapy were not associated with the development of severe oral mucositis.ConclusionsThis study showed that vitamin D deficiency occurs frequently in pediatric ALL patients above the age of 4years. A decrease in 25(OH)D-3 levels during MTX therapy was observed in children with ALL that developed severe oral mucositis.