Vitamin D Deficiency and Oral Mucositis in Hematopoietic Stem Cell Transplantation: A Cross-Sectional Observation
Backgrounds: One of the most frequent complications of high-dose chemotherapy regimen before hematopoietic stem cell transplantation (HSCT) is oral mucositis (OM). Vitamin D (VD) has well-known immunoregulatory, anti-inflammatory, and antioxidant properties.
Objectives: This study aimed to evaluate the association of baseline VD levels with OM as well as neutrophil and platelet engraftments in patients with multiple myeloma, Hodgkin’s and non-Hodgkin’s lymphoma after autologous HSCT.
Methods: A sample of 71 patients was included after obtaining informed consent. Serum samples were collected in the morning prior to the administration of conditioning regimen to measure the baseline 25-OH-D. OM was examined daily during hospital stay. The WHO scale was used for scoring the OM. Absolute neutrophil count and platelet count were determined daily from transplantation until engraftment.
Results: Patients aged between 18 to 65 years. Mean length of hospital stay was 15.8±5.7 days. OM was detected in 44/71 (62.0%) of patients. Mean time to the engraftment of neutrophils and platelets were 11.8±4.0 and 17.2±7.3 days, respectively. Mean level of baseline 25-OH-D was 17.5±14.0 ng/ml. VD deficiency (<20 ng/ml) was diagnosed in 51/71 (71.8%) of patients. No association between baseline 25-OH-D levels and the incidence of OM (P=0.69) or OM grade 3-4 (P=0.46) was found. No significant correlations were detected between the baseline 25-OH-D and engraftment time of neutrophils (P=0.46) or platelets (P=0.17).
Conclusions: The prevalence of VD deficiency was high among adult HSCT patients at the time of transplantation. No association was found between low baseline VD with post-HSCT OM and engraftment time.
2. Worthington HV, Clarkson JE, Bryan G, Furness S, Glenny AM, Littlewood A, et al. Interventions for preventing oral mucositis for patients with cancer receiving treatment. Cochrane Database of Systematic Reviews. 2011(4).
3. Sonis ST. The pathobiology of mucositis. Nature Reviews Cancer. 2004;4:277.
4. Di Rosa M, Malaguarnera M, Nicoletti F, Malaguarnera L. Vitamin D3: a helpful immuno-modulator. Immunology. 2011;134(2):123-39.
5. Medrano M, Carrillo-Cruz E, Montero I, Perez-Simon JA. Vitamin D: effect on haematopoiesis and immune system and clinical applications. Int J Mol Sci. 2018;19(9):2663.
6. Hopkins MH, Owen J, Ahearn T, Fedirko V, Flanders WD, Jones DP, et al. Effects of supplemental vitamin D and calcium on biomarkers of inflammation in colorectal adenoma patients: a randomized, controlled clinical trial. Cancer Prevention Research. 2011;4(10):1645-54.
7. Duncan CN, Vrooman L, Apfelbaum EM, Whitley K, Bechard L, Lehmann LE. 25-Hydroxy vitamin D deficiency following pediatric hematopoietic stem cell transplant. Biology of Blood and Marrow Transplant. 2011;17(5):749-53.
8. Hansson ME, Norlin A-C, Omazic B, Wikström A-C, Bergman P, Winiarski J, et al. Vitamin D levels affect outcome in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(10):1537-43.
9. Campos DJ, Biagini GLK, Funke VAM, Bonfim CMS, Boguszewski CL, Borba VZC. Vitamin D deficiency in children and adolescents submitted to hematopoietic stem cell transplantation. Revista brasileira de hematologia e hemoterapia. 2014;36(2):126-31.
10. von Bahr L, Blennow O, Alm J, Björklund A, Malmberg KJ, Mougiakakos D, et al. Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation. Bone Marrow Transplant. 2015;50(9):1217-23.
11. Wallace G, Jodele S, Howell J, Myers KC, Teusink A, Zhao X, et al. Vitamin D deficiency and survival in children after hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2015;21(9):1627-31.
12. Wallace G, Jodele S, Myers KC, Dandoy CE, El-Bietar J, Nelson A, et al. Vitamin D deficiency in pediatric hematopoietic stem cell transplantation patients despite both standard and aggressive supplementation. Biol Blood Marrow Transplant. 2016;22(7):1271-4.
13. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-81.
14. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know. The Journal of Clinical Endocrinology & Metabolism. 2011;96(1):53-8.
15. Rosenblatt J, Bissonnette A, Ahmad R, Wu Z, Vasir B, Stevenson K, et al. Immunomodulatory effects of vitamin D: implications for GvHD. Bone Marrow Transplant. 2010;45(9):1463-8.
16. Hamidieh AA, Sherafatmand M, Mansouri A, Hadjibabaie M, Ashouri A, Jahangard-Rafsanjani Z, et al. Calcitriol for oral mucositis prevention in patients with Fanconi anemia undergoing hematopoietic SCT: a double-blind, randomized, placebo-controlled trial. Am J Ther. 2016;23(6):e1700-e8.
17. Nejatinamini S, Debenham BJ, Clugston RD, Mawani A, Parliament M, Wismer WV, et al. Poor Vitamin Status is Associated with Skeletal Muscle Loss and Mucositis in Head and Neck Cancer Patients. Nutrients. 2018;10(9):1236.
18. Oosterom N, Dirks NF, Heil SG, de Jonge R, Tissing WJE, Pieters R, et al. A decrease in vitamin D levels is associated with methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2019;27(1):183-90.
19. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911-30.
20. Bensinger W, Schubert M, Ang K, Brizel D, Brown E, Eilers J, et al. NCCN task force report: prevention and management of mucositis in cancer care. Journal of the National Comprehensive Cancer Network: JNCCN. 2008;6:S1-21.
21. Ros-Soto J, Anthias C, Madrigal A, Snowden JA. Vitamin D: is it important in haematopoietic stem cell transplantation? a review. Bone Marrow Transplant. 2018(DOI: 10.1038/s41409-018-0377-0).
22. Sun J. Vitamin D and mucosal immune function. Current opinion in gastroenterology. 2010;26(6):591-5.
23. Lim WC, Hanauer SB, Li YC. Mechanisms of disease: vitamin D and inflammatory bowel disease. Nat Clin Pract Gastroenterol Hepatol. 2005;2(7):308-15.
24. Zhang YG, Wu S, Sun J. Vitamin D, vitamin D receptor, and tissue barriers. Tissue Barriers. 2013;1(1).
25. Zhang YG, Wu S, Lu R, Zhou D, Zhou J, Carmeliet G, et al. Tight junction CLDN2 gene is a direct target of the vitamin D receptor. Sci Rep. 2015;5:10642.
26. Kitchen D, Hughes B, Gill I, O'Brien M, Rumbles S, Ellis P, et al. The relationship between vitamin D and chemotherapy-induced toxicity - a pilot study. Br J Cancer. 2012;107(1):158-60.