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Vitamin D levels and busulphan kinetics in patients undergoing hematopoietic stem cell transplantation, a multicenter study
Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Suez Canal Univ, Egypt.
Karolinska Inst, Sweden; Karolinska Univ Hosp Huddinge, Sweden; Karolinska Univ Hosp Huddinge, Sweden.
Karolinska Inst, Sweden; Karolinska Univ Hosp Huddinge, Sweden; Karolinska Univ Hosp Huddinge, Sweden.
Karolinska Inst, Sweden; Karolinska Univ Hosp Huddinge, Sweden; Karolinska Univ Hosp Huddinge, Sweden.
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2021 (English)In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 56, p. 807-817Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
SPRINGERNATURE , 2021. Vol. 56, p. 807-817
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Hematology
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URN: urn:nbn:se:liu:diva-171539DOI: 10.1038/s41409-020-01091-yISI: 000581834100001PubMedID: 33087877OAI: oai:DiVA.org:liu-171539DiVA, id: diva2:1502716
Note

Funding Agencies|Swedish Cancer SocietySwedish Cancer Society [CAN2014/759]; Swedish Childhood Cancer Foundation [PR2017-0083]; KI funds [2018-02377, 2018-02344]; Radiumhemmets Research Funding [161082]

Available from: 2020-11-20 Created: 2020-11-20 Last updated: 2022-05-25

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El-Serafi, AhmedLotfi, Kourosh

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El-Serafi, AhmedLotfi, KouroshEl-Serafi, Ibrahim
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Division of Surgery, Orthopedics and OncologyFaculty of Medicine and Health SciencesDepartment of HaematologyDivision of Clinical Chemistry and Pharmacology
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Bone Marrow Transplantation
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