Original Article

High Prevalence of Vitamin D Deficiency in Newly Diagnosed Acute Myeloid Leukemia Patients and Its Adverse Outcome


Background: Although several studies have supported a preventive and therapeutic role of vitamin D (Vit D) for different types of cancers, we face insufficient documentation in acute myeloid leukemia (AML). So, we examined whether the serum calcidiol (25(OH)D) levels at the time of induction therapy have any impact on response and relapse in AML patients.
Subjects and Methods: Blood samples were collected from 65 patients on days 0 and 28th of treatment to evaluate serum concentration of 25(OH)D and its effects on complete remission (CR) achievement, relapse rate and hospitalization length.
Results: Of the 65 patients who were included in the study, 38 were male (58.5%) and 27 were female (41.5%). Median age at the time of treatment was 37 years (range 15-68). 6% of the participants were older than 60 years. In regard to 25(OH)D levels, 81.5% of AML patients were deficient (levels <20 ng/ml). There was a significant difference in CR between patients with sufficient and deficient level of 25(OH)D. Deficient patients had longer length of hospitalization than those with sufficient levels. Also Vitamin D deficient patients had higher serum ALP levels. The mean level of 25(OH)D on treatment day 28th in our study was significantly lower than the baseline value.
Conclusion: The results of the study showed that serum 25(OH)D levels deficiency was highly prevalent among Iranian AML patients. Furthermore, higher Vit D levels in AML patients were associated with better outcome in these patients.

Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453-74.

Meyers CA, Albitar M, Estey E. Cognitive impairment, fatigue, and cytokine levels in patients with acute myelogenous leukemia or myelodysplastic syndrome. Cancer. 2005;104(4):788-93.

Weber L, Stricker S, Williams C, et al. Adult hematologic malignancies. In: Kirstein M, editor. Applied therapeutics: the clinical use of drugs. 10th ed: Wolters Kluwer/Lipincot William & Wilkins; 2013. p. 2172-96.

Bennett JM, Catovsky D, Daniel MT, et al. Proposed revised criteria for the classification of acute myeloid leukemia: a report of the French-American-British Cooperative Group. Ann Intern Med. 1985;103(4):620-5.

Sekeres MA, Elson P, Kalaycio ME, et al. Time from diagnosis to treatment initiation predicts survival in younger, but not older, acute myeloid leukemia patients. Blood. 2009;113(1):28-36.

Bertoli S, Bérard E, Huguet F, et al. Time from diagnosis to intensive chemotherapy initiation does not adversely impact the outcome of patients with acute myeloid leukemia. Blood. 2013;121(14):2618-26.

Wallen H, Gooley TA, Deeg HJ, et al. Ablative allogeneic hematopoietic cell transplantation in adults 60 years of age and older. J Clin Oncol. 2005;23(15):3439-46.

Gyurkocza B, Storb R, Storer BE, et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J Clin Oncol. 2010:JCO. 2009.27. 1460.

Bertz H, Potthoff K, Finke J. Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia. J Clin Oncol. 2003;21(8):1480-4.

Christakos S, Dhawan P, Verstuyf A, et al. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 2016;96(1):365-408.

Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-81.

Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab. 2009;94(1):26-34.

Herrmann M, Farrell C-JL, Pusceddu I, et al. Assessment of vitamin D status–a changing landscape. Clin Chem Lab Med. 2017; 55(1):3-26.

Holick MF, editor High prevalence of vitamin D inadequacy and implications for health. Mayo Clin Proc. 2006; 81(3):353-73.

Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48-54.

Timonen T. A hypothesis concerning deficiency of sunlight, cold temperature, and influenza epidemics associated with the onset of acute lymphoblastic leukemia in northern Finland. Ann Hematol. 1999;78(9):408-14.

Hassan IB, Islam SI, Alizadeh H, et al. Acute leukemia among the adult population of United Arab Emirates: an epidemiological study. Leuk Lymphoma. 2009;50(7):1138-47.

Boscoe FP, Schymura MJ. Solar ultraviolet-B exposure and cancer incidence and mortality in the United States, 1993–2002. BMC cancer. 2006;6(1):1.

Miyaura C, Abe E, Kuribayashi T, et al. 1α, 25-Dihydroxyvitamin D 3 induces differentiation of human myeloid leukemia cells. Biochem Biophys Res Commun. 1981;102(3):937-43.

Drake MT, Maurer MJ, Link BK, et al. Vitamin D insufficiency and prognosis in non-Hodgkin's lymphoma. J Clin Oncol. 2010:JCO. 2010.28. 6674.

Shanafelt TD, Drake MT, Maurer MJ, et al. Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia. Blood. 2011;117(5):1492-8.

Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. The Am J Clin Nutr. 2008;87(4):1080S-6S.

Rowe JM, Neuberg D, Friedenberg W, et al. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. Blood. 2004;103(2):479-85.

Heshmat R, Mohammad K, Majdzadeh S, et al. Vitamin D deficiency in Iran: A multi-center study among different urban areas. Iran J Public Health. 2008;37(suppl).

Alizadeh N, Khalili H, Mohammadi M, et al. Serum Vitamin D levels at admission predict the length of intensive care unit stay but not in-hospital mortality of critically ill surgical patients. J Res Pharm Pract. 2015;4(4):193.

Lips P. Vitamin D status and nutrition in Europe and Asia. J Steroid Biochem Mol Biol. 2007;103(3):620-5.

Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62(1):10-29.

Sanaat Z, Nouri M, Hajipour B, et al. Evaluation of copper, zinc, Cu/Zn, and VEGF in patients with AML in Iran. Iran J Cancer Prev. 2011;4(4):151.

Ashrafi F, Shahnazari R, Samimi MA, et al. Results of treatment of acute myeloid leukemia in central part of Iran. Adv Biomed Res. 2013; 2:51.

Ma Y, Johnson CS, Trump DL. Chapter Sixteen-Mechanistic Insights of Vitamin D Anticancer Effects. Vitam Horm. 2016;100:395-431.

Radujkovic A, Schnitzler P, Ho AD, et al. Low serum vitamin D levels are associated with shorter survival after first-line azacitidine treatment in patients with myelodysplastic syndrome and secondary oligoblastic acute myeloid leukemia. Clin Nutr. 2017 Apr;36(2):542-551.

Lee HJ, Muindi JR, Tan W, et al. Low 25 (OH) vitamin D3 levels are associated with adverse outcome in newly diagnosed, intensively treated adult acute myeloid leukemia. Cancer. 2014;120(4):521-9.

Thompson T, Andreeff M, Studzinski GP, et al. 1, 25-dihydroxyvitamin D3 enhances the apoptotic activity of MDM2 antagonist nutlin-3a in acute myeloid leukemia cells expressing wild-type p53. Mol Cancer Ther. 2010;9(5):1158-68.

Jiang F, Bao J, Li P, et al. Induction of ovarian cancer cell apoptosis by 1, 25-dihydroxyvitamin D3 through the down-regulation of telomerase. J Biol Chem. 2004;279(51):53213-21.

Gocek E, Studzinski GP. Vitamin D and differentiation in cancer. Crit Rev Clin Lab Sci. 2009;46(4):190-209.

Nowak D, Stewart D, Koeffler HP. Differentiation therapy of leukemia: 3 decades of development. Blood. 2009;113(16):3655-65.

Hughes PJ, Brown G. 1α, 25‐dihydroxyvitamin D3‐mediated stimulation of steroid sulphatase activity in myeloid leukaemic cell lines requires VDRnuc‐mediated activation of the RAS/RAF/ERK‐MAP kinase signalling pathway. J Cell Biochem. 2006;98(3):590-617.

Krishnan AV, Feldman D. Mechanisms of the anti-cancer and anti-inflammatory actions of vitamin D. Annu Rev Pharmacol Toxicol. 2011;51:311-36.

McKinney JD, Bailey BA, Garrett LH, et al. Relationship between vitamin D status and ICU outcomes in veterans. J Am Med Dir Assoc. 2011;12(3):208-11.

Higgins DM, Wischmeyer PE, Sillau SH, et al. Relationship of vitamin D deficiency to clinical outcomes in critically ill patients. JPEN J Parenter Enteral Nutr. 2012;36(6):713-20.

Kempker JA, Han JE, Tangpricha V, et al. Vitamin D and sepsis: An emerging relationship. Dermatoendocrinol. 2012;4(2):101-8.

Ginde AA, Mansbach JM, Camargo CA. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009;169(4):384-90.

Ghashut RA, Talwar D, Kinsella J, et al. The effect of the systemic inflammatory response on plasma vitamin 25 (OH) D concentrations adjusted for albumin. PloS one. 2014;9(3):e92614.

Kennel KA, Drake MT, Hurley DL, editors. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010; 85(8):752-7

Fakih MG, Trump DL, Johnson CS, et al. Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal cancer. Int J Colorectal Dis. 2009;24(2):219-24.

IssueVol 11, No 3 (2017) QRcode
SectionOriginal Article(s)
Acute myeloid leukemia (AML) Vitamin D Remission Relapse

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Seyedalipour F, Mansouri A, Vaezi M, Gholami K, Hadjibabaie M, Ghavamzadeh A. High Prevalence of Vitamin D Deficiency in Newly Diagnosed Acute Myeloid Leukemia Patients and Its Adverse Outcome. Int J Hematol Oncol Stem Cell Res. 2017;11(3):209-216.