The Role of Vitamin D in Hematopoietic Stem Cell Transplantation: Implications for Graft-versus-Host Disease-A Narrative Review

Overview

Journal Nutrients

Date 2024 Sep 14

PMID 39275291

Authors

Stefano Mancin

Giovanni Cangelosi

Sofia Matteucci

Sara Morales Palomares

Mauro Parozzi

Elena Sandri

Marco Sguanci

Michela Piredda

Affiliations

Soon will be listed here.

Abstract

Introduction/aim: Vitamin D plays a crucial role in immune modulation, which may influence the development of graft-versus-host disease (GvHD) in patients undergoing hematopoietic stem cell transplantation (HSCT). This study aims to evaluate the impact of vitamin D levels and supplementation on the incidence of GvHD in HSCT patients.

Methods: A narrative review was conducted across PubMed/Medline, Cochrane Library, CINAHL, and Embase databases.

Results: The reviewed studies indicated widespread vitamin D deficiency among HSCT patients, with baseline levels ranging from 12.8 to 29.2 ng/mL. Supplementation protocols varied significantly, with dosages ranging from 1000 IU/day to 60,000 IU/week. Post-supplementation levels improved in some studies. Studies exploring the relationship between vitamin D and GvHD showed mixed results. Lower baseline vitamin D levels were associated with an increased risk of acute GvHD in some studies, while others found no significant correlation. However, a significant association between low levels of vitamin D and the incidence of chronic GvHD was observed.

Conclusion: Vitamin D deficiency is prevalent in HSCT patients and may influence the risk of developing chronic GvHD. Future research should focus on larger and more rigorous studies to determine the optimal role of vitamin D as an adjuvant therapy in the context of HSCT.

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References

Ros-Soto J, Anthias C, Madrigal A, Snowden J . Vitamin D: is it important in haematopoietic stem cell transplantation? A review. Bone Marrow Transplant. 2018; 54(6):810-820. DOI: 10.1038/s41409-018-0377-0. View

Arain A, Matthiesen C . Vitamin D deficiency and graft-versus-host disease in hematopoietic stem cell transplant population. Hematol Oncol Stem Cell Ther. 2018; 12(3):133-139. DOI: 10.1016/j.hemonc.2018.08.001. View

Glotzbecker B, Ho V, Aldridge J, Kim H, Horowitz G, Ritz J . Low levels of 25-hydroxyvitamin D before allogeneic hematopoietic SCT correlate with the development of chronic GVHD. Bone Marrow Transplant. 2012; 48(4):593-7. DOI: 10.1038/bmt.2012.177. View

Funke V, Moreira M, Vigorito A . Acute and chronic Graft-versus-host disease after hematopoietic stem cell transplantation. Rev Assoc Med Bras (1992). 2016; 62 Suppl 1:44-50. DOI: 10.1590/1806-9282.62.suppl1.44. View

Zhang N, Wu J, Wang Q, Liang Y, Li X, Chen G . Global burden of hematologic malignancies and evolution patterns over the past 30 years. Blood Cancer J. 2023; 13(1):82. PMC: 10188596. DOI: 10.1038/s41408-023-00853-3. View

Beres A, Drobyski W . The role of regulatory T cells in the biology of graft versus host disease. Front Immunol. 2013; 4:163. PMC: 3690651. DOI: 10.3389/fimmu.2013.00163. View

Kostoglou-Athanassiou I, Athanassiou P, Lyraki A, Raftakis I, Antoniadis C . Vitamin D and rheumatoid arthritis. Ther Adv Endocrinol Metab. 2013; 3(6):181-7. PMC: 3539179. DOI: 10.1177/2042018812471070. View

Arai S, Arora M, Wang T, Spellman S, He W, Couriel D . Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2014; 21(2):266-74. PMC: 4326247. DOI: 10.1016/j.bbmt.2014.10.021. View

von Bahr L, Blennow O, Alm J, Bjorklund A, Malmberg K, Mougiakakos D . Increased incidence of chronic GvHD and CMV disease in patients with vitamin D deficiency before allogeneic stem cell transplantation. Bone Marrow Transplant. 2015; 50(9):1217-23. DOI: 10.1038/bmt.2015.123. View

10.

Pirsl F, Curtis L, Steinberg S, Tella S, Katic M, Dobbin M . Characterization and Risk Factor Analysis of Osteoporosis in a Large Cohort of Patients with Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2016; 22(8):1517-1524. PMC: 4949073. DOI: 10.1016/j.bbmt.2016.04.012. View

11.

Moreno D, Cid J . Graft-versus-host disease. Med Clin (Barc). 2018; 152(1):22-28. DOI: 10.1016/j.medcli.2018.07.012. View

12.

Arora M, Cutler C, Jagasia M, Pidala J, Chai X, Martin P . Late Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2015; 22(3):449-55. PMC: 4787270. DOI: 10.1016/j.bbmt.2015.10.018. View

13.

Lim Y, Baek K, Kim H, Lee S, Lee J, Kang M . Changes in trabecular bone score and bone mineral density following allogeneic hematopoietic stem cell transplantation. Bone. 2019; 124:40-46. DOI: 10.1016/j.bone.2019.04.004. View

14.

Li Pira G, Di Cecca S, Montanari M, Moretta L, Manca F . Specific removal of alloreactive T-cells to prevent GvHD in hemopoietic stem cell transplantation: rationale, strategies and perspectives. Blood Rev. 2016; 30(4):297-307. DOI: 10.1016/j.blre.2016.03.001. View

15.

Wang Y, He S, Calendo G, Bui T, Tian Y, Lee C . Tissue-infiltrating alloreactive T cells require Id3 to deflect PD-1-mediated immune suppression during GVHD. Blood. 2023; 143(2):166-177. PMC: 10797551. DOI: 10.1182/blood.2023021126. View

16.

Flamann C, Peter K, Kreutz M, Bruns H . Regulation of the Immune Balance During Allogeneic Hematopoietic Stem Cell Transplantation by Vitamin D. Front Immunol. 2019; 10:2586. PMC: 6848223. DOI: 10.3389/fimmu.2019.02586. View

17.

Charoenngam N . Vitamin D and Rheumatic Diseases: A Review of Clinical Evidence. Int J Mol Sci. 2021; 22(19). PMC: 8508879. DOI: 10.3390/ijms221910659. View

18.

Toenges R, Greinix H, Lawitschka A, Halter J, Baumgartner A, Simon A . Current practice in nutrition after allogeneic hematopoietic stem cell transplantation - Results from a survey among hematopoietic stem cell transplant centers. Clin Nutr. 2021; 40(4):1571-1577. DOI: 10.1016/j.clnu.2021.02.030. View

19.

Caprio M, Infante M, Calanchini M, Mammi C, Fabbri A . Vitamin D: not just the bone. Evidence for beneficial pleiotropic extraskeletal effects. Eat Weight Disord. 2016; 22(1):27-41. DOI: 10.1007/s40519-016-0312-6. View

20.

Sukhera J . Narrative Reviews: Flexible, Rigorous, and Practical. J Grad Med Educ. 2022; 14(4):414-417. PMC: 9380636. DOI: 10.4300/JGME-D-22-00480.1. View