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Vitamin D levels and busulphan kinetics in patients undergoing hematopoietic stem cell transplantation, a multicenter study

El-Serafi, Ahmed ; He, Rui ; Zheng, Wenyi ; Benkossou, Fadwa ; Oerther, Sandra ; Zhao, Ying ; Mellgren, Karin ; Gustafsson, Britt ; Heilmann, Carsten and Kanerva, Jukka , et al. (2021) In Bone Marrow Transplantation 56(4). p.807-817
Abstract

Vitamin D (Vit-D), an essential nutrient, interacts with different drugs including chemotherapeutic agents like busulphan, an alkylating agent used for conditioning prior to stem cell transplantation. The correlation between Vit-D plasma levels and busulphan clearance was investigated in an uncontrolled prospective study in patients and mice. Plasma 25(OH)D levels were measured and busulphan pharmacokinetics calculated in 81 patients. Adults received oral busulphan (n = 34) while children received busulphan orally (n = 19) or intravenously (n = 28). Patients received no Vit-D supplementation. To confirm our findings, pharmacokinetics after a single dose of busulphan (oral or intravenous) were evaluated in two groups of mice (n = 60)... (More)

Vitamin D (Vit-D), an essential nutrient, interacts with different drugs including chemotherapeutic agents like busulphan, an alkylating agent used for conditioning prior to stem cell transplantation. The correlation between Vit-D plasma levels and busulphan clearance was investigated in an uncontrolled prospective study in patients and mice. Plasma 25(OH)D levels were measured and busulphan pharmacokinetics calculated in 81 patients. Adults received oral busulphan (n = 34) while children received busulphan orally (n = 19) or intravenously (n = 28). Patients received no Vit-D supplementation. To confirm our findings, pharmacokinetics after a single dose of busulphan (oral or intravenous) were evaluated in two groups of mice (n = 60) receiving high or standard-level Vit-D supplementation. Both busulphan clearance (P < 0.0001) and 25(OH)D levels (P = 0.0004) were significantly higher in adults compared to children. A significant negative correlation (P = 0.041) was found between busulphan clearance and 25(OH)D levels in children treated orally. No such correlation was observed in adults or in children receiving intravenous busulphan. In addition, no significant effect of Vit-D levels on busulphan pharmacokinetics in mice regardless of the administration route. In conclusion, 25(OH)D can affect oral busulphan pharmacokinetics in children and its level should be considered when personalizing oral busulphan treatment. Further studies are warranted to confirm the underlying mechanisms.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Bone Marrow Transplantation
volume
56
issue
4
pages
807 - 817
publisher
Nature Publishing Group
external identifiers
  • pmid:33087877
  • scopus:85093109884
ISSN
0268-3369
DOI
10.1038/s41409-020-01091-y
language
English
LU publication?
no
id
1955b100-b043-4c71-bd0f-a8ac32012401
date added to LUP
2020-11-12 14:10:24
date last changed
2024-03-20 19:40:46
@article{1955b100-b043-4c71-bd0f-a8ac32012401,
  abstract     = {{<p>Vitamin D (Vit-D), an essential nutrient, interacts with different drugs including chemotherapeutic agents like busulphan, an alkylating agent used for conditioning prior to stem cell transplantation. The correlation between Vit-D plasma levels and busulphan clearance was investigated in an uncontrolled prospective study in patients and mice. Plasma 25(OH)D levels were measured and busulphan pharmacokinetics calculated in 81 patients. Adults received oral busulphan (n = 34) while children received busulphan orally (n = 19) or intravenously (n = 28). Patients received no Vit-D supplementation. To confirm our findings, pharmacokinetics after a single dose of busulphan (oral or intravenous) were evaluated in two groups of mice (n = 60) receiving high or standard-level Vit-D supplementation. Both busulphan clearance (P &lt; 0.0001) and 25(OH)D levels (P = 0.0004) were significantly higher in adults compared to children. A significant negative correlation (P = 0.041) was found between busulphan clearance and 25(OH)D levels in children treated orally. No such correlation was observed in adults or in children receiving intravenous busulphan. In addition, no significant effect of Vit-D levels on busulphan pharmacokinetics in mice regardless of the administration route. In conclusion, 25(OH)D can affect oral busulphan pharmacokinetics in children and its level should be considered when personalizing oral busulphan treatment. Further studies are warranted to confirm the underlying mechanisms.</p>}},
  author       = {{El-Serafi, Ahmed and He, Rui and Zheng, Wenyi and Benkossou, Fadwa and Oerther, Sandra and Zhao, Ying and Mellgren, Karin and Gustafsson, Britt and Heilmann, Carsten and Kanerva, Jukka and Lotfi, Kourosh and Toporski, Jacek and Sundin, Mikael and Höglund, Martin and Mattsson, Jonas and El-Serafi, Ibrahim and Hassan, Moustapha}},
  issn         = {{0268-3369}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{807--817}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Bone Marrow Transplantation}},
  title        = {{Vitamin D levels and busulphan kinetics in patients undergoing hematopoietic stem cell transplantation, a multicenter study}},
  url          = {{http://dx.doi.org/10.1038/s41409-020-01091-y}},
  doi          = {{10.1038/s41409-020-01091-y}},
  volume       = {{56}},
  year         = {{2021}},
}