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Variations in 1α,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 serum levels during allogeneic bone marrow transplantation

Bone Marrow Transplantation volume 33, pages 871–873 (2004)Cite this article

Besides its well-known effect on calcium homeostasis, the active form of vitamin D 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates the growth and differentiation of cancer cells and inhibits, alone or in combination with cyclosporin A, autoimmune disease and graft rejection in several experimental transplantation models. The immunosuppressive effect of 1,25(OH)2D3 is based on the modulation of immune cell differentiation and function.11,25(OH)2D3 positively influences the differentiation of monocytes into macrophages, whereas the function of lymphocytes and the differentiation of dendritic cells (DC) are suppressed.2 Vitamin D receptor (VDR) deficient mice show an unresponsiveness to 1,25(OH)2D3 and have increased numbers of DC in lymph nodes, suggesting a physiologically relevant inhibition of DC differentiation by 1,25(OH)2D3.3 As inactivation of host DC has been proposed to prevent graft–versus-host disease (GvHD) in allogeneic bone marrow transplantation (BMT), the inhibition of DC differentiation by 1,25(OH)2D3 could prevent T-cell activation in the course of alloreactions. Accordingly, it has been shown that vitamin D analogs prevent acute GvHD in rat BMT and that the VDR gene polymorphism associates with GvHD and survival.4,5 Up to now, no data are available on the endogenous serum levels of vitamin D metabolites during the course of BMT. In this study we measured 25-hydroxyvitamin D3 (25(OH)D3) and 1,25(OH)2D3 in consecutive serum samples of 48 patients before and after allogeneic BMT.

Patients received standard conditioning consisting of fractionated total body irradiation (8–12 Gy) followed by cyclophosphamide 2 × 60 mg/kg or reduced-intensity conditioning including fludarabin/BCNU and melphalan.6 Cyclosporin and a short course of methotrexate or mycophenolate mofetil were used for prevention of GvHD. Prednisolone at a dose of 2 mg/kg was used for first-line treatment of GvHD, monoclonal antibodies blocking IL-2 the receptor (ZenapaxR) or TNF-antagonists (etanercept) were given to patients with resistant or relapsing acute GvHD. Chronic GvHD was treated with CsA and prednisolone or extracorporal photopheresis. Besides creatinine, CsA levels and other routine parameters, analyses of 25(OH)D3 and 1,25(OH)2D3 were performed. Informed consent for collection of serum samples had been obtained from all patients.

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Authors and Affiliations

  1. Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany

    M Kreutz, G Eissner, J Hahn, R Andreesen & E Holler

  2. Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany

    W Drobnik

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  1. M Kreutz
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  2. G Eissner
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Kreutz, M., Eissner, G., Hahn, J. et al. Variations in 1α,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 serum levels during allogeneic bone marrow transplantation. Bone Marrow Transplant 33, 871–873 (2004). https://doi.org/10.1038/sj.bmt.1704448

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