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Treatment of low-risk myelodysplastic syndromes with high-dose daily oral cholecalciferol (2000–4000 IU vitamin D3)

Leukemia volume 21, pages 1089–1092 (2007)Cite this article

The hormonally active form of vitamin D3, 1,25(OH)2D3, inhibits the proliferation and induces the differentiation of normal and leukemic myeloid cells.1 The synthesis of 1,25(OH)2D3 begins with the production of vitamin D3 (cholecalciferol) after 7-dehydrocholesterol in the skin is exposed to ultraviolet radiation (wavelength 290–315 nm). To become biologically active, vitamin D undergoes two hydroxylations: the first in the liver, forming 25-hydroxyvitamin D (25(OH)D), the prohormone and major circulating form of vitamin D; the second at the 1 α position, forming 1,25(OH)2D, the hormonal form of vitamin D. Although the kidney is the major source of serum 1,25(OH)2D, the enzyme that converts 25(OH)D to 1,25(OH)2D, 1α-hydroxylase, is also present in a number of nonrenal cells, for example, prostate cells and activated macrophages and monocytes. These cells use 1,25(OH)2D that is produced in a ‘micro-endocrine’ manner in which the hormone locally controls cell proliferation and differentiation. Numerous case reports and case series of patients with myelodysplastic syndromes (MDS) have reported beneficial effects of 1,25(OH)2D3 or analogues. The use of the 1,25(OH)2D3 prohormone in MDS had been investigated by Mellibovsky et al.,2 who used 266 μg 25(OH)D3 3 times a week in five patients. Three patients remained stable and one showed a major response. We hypothesized that by providing ample supply of cholecalciferol, the ‘pre-prohormone’, we might alter the phenotype of low-risk MDS.

We conducted an open-label clinical trial in patients with low- and intermediate-1-(INT-1) risk MDS with oral 2000–4000 IU cholecalciferol (vitamin D3) daily for up to 12 months. The primary outcome was hematological improvement as defined by the revised International Working Group criteria. Secondary outcomes were toxicity, serum levels of 25(OH)D and quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy, General Measures (FACT-G) and Functional Assessment of Chronic Illness Therapy, Fatigue Scale (FACIT-F) scales.

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References

  1. Abe E, Miyaura C, Sakagami H, Takeda M, Konno K, Yamazaki T et al. Differentiation of mouse myeloid leukemia cells induced by 1α,25-dihydroxyvitamin D3 . Proc Natl Acad Sci USA 1981; 78: 4990–4995.

    Article  CAS  PubMed  Google Scholar 

  2. Mellibovsky L, Diez A, Perez-Vila E, Serrano S, Nacher M, Aubia J et al. Vitamin D treatment in myelodysplastic syndromes. Br J Haematol 1998; 100: 516–520.

    Article  CAS  PubMed  Google Scholar 

  3. Chen TC, Turner AK, Holick MF . Methods for the determination of the circulating concentration of 25-hydroxyvitamin D. J Nutr Biochem 1990; 1: 315–319.

    Article  CAS  PubMed  Google Scholar 

  4. Brucker PS, Yost K, Cashy J, Webster K, Cella D . General population and cancer patient norms for the Functional Assessment of Cancer Therapy – General (FACT-G). Eval Health Prof 2005; 28: 192–211.

    Article  PubMed  Google Scholar 

  5. Cella D, Eton DT, Lai JS, Peterman AH, Merkel DE . Combining anchor and distribution-based methods to derive minimal clinically important differences on the Functional Assessment of Cancer Therapy (FACT) anemia and fatigue scales. J Pain Symptom Manage 2002; 24: 547–561.

    Article  PubMed  Google Scholar 

  6. Jorde R, Waterloo K, Saleh F, Haug E, Svartberg J . Neuropsychological function in relation to serum parathyroid hormone and serum 25-hydroxyvitamin D levels. J Neurol 2006; 253: 464–470.

    Article  CAS  PubMed  Google Scholar 

  7. Lansdowne ATG, Provost SC . Vitamin D3 enhances mood in healthy subjects during winter. Psychopharmacology 1998; 135: 319.

    Article  CAS  PubMed  Google Scholar 

  8. Vieth R, Kimball S, Hu A, Walfish PG . Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Nutr J 2004; 3: 8.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported, in part, by the Doug Coley Fund for Leukemia Research, The Leukemia Research Fund of Wake Forest University (to IM) and by a supplementary grant on Complementary and Alternative Medicine to the Comprehensive Cancer Center of Wake Forest University Core Grant 5 P30 CA 12197-27S1 (led by GGS).

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Authors and Affiliations

  1. Department of Internal Medicine, Section on Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    I Molnár, N Stark, B L Powell, J Cruz & D D Hurd

  2. Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    J Lovato

  3. Vitamin D, Bone & Mineral Laboratories, Boston University School of Medicine, Boston, MA, USA

    J S Mathieu, T C Chen & M F Holick

  4. Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC, USA

    I Molnár, N Stark, J Lovato, B L Powell, J Cruz, D D Hurd, S Cambra, R P McQuellon & G G Schwartz

  5. Department of Cancer Biology and Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    G G Schwartz

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  1. I Molnár
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Correspondence to G G Schwartz.

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Molnár, I., Stark, N., Lovato, J. et al. Treatment of low-risk myelodysplastic syndromes with high-dose daily oral cholecalciferol (2000–4000 IU vitamin D3). Leukemia 21, 1089–1092 (2007). https://doi.org/10.1038/sj.leu.2404601

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