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

• Published in: Supportive care in cancer Vol. 27; no. 1; pp. 183 - 190
• Main Authors: Oosterom, N., Dirks, N. F., Heil, S. G., de Jonge, R., Tissing, W. J. E., Pieters, R., van den Heuvel-Eibrink, M. M., Heijboer, A. C., Pluijm, S. M. F.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-01-2019; Springer; Springer Nature B.V
• Subjects: Adolescent; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Child; Child, Preschool; Cohort Studies; Dose-Response Relationship, Drug; Female; Humans; Infant; Leukemia; Male; Medicine; Medicine & Public Health; Methotrexate - administration & dosage; Methotrexate - adverse effects; Netherlands - epidemiology; Nursing; Nursing Research; Oncology; Original; Original Article; Pain Medicine; Pediatrics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - epidemiology; Prevalence; Rehabilitation Medicine; Stomatitis - blood; Stomatitis - chemically induced; Stomatitis - complications; Stomatitis - epidemiology; Vitamin D; Vitamin D - blood; Vitamin D Deficiency - blood; Vitamin D Deficiency - complications; Vitamin D Deficiency - epidemiology; Vitamin deficiency; Withholding Treatment; Young Adult; Netherlands; Oral mucositis; Vitamin D; Acute lymphoblastic leukemia; Methotrexate
• ISSN: 0941-4355; 1433-7339
• DOI: 10.1007/s00520-018-4312-0

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)D
3
) and 24,25-dihydroxyvitamin D (24,25(OH)
2
D
3
) levels in 99 children with ALL before the start of 4 × 5 g/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 < 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)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.
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)D
3
levels during MTX therapy was observed in children with ALL that developed severe oral mucositis.