Vitamin D May Affect GVHD Rates in Stem Cell Transplantation, Review Finds

Physicians ought to consider vitamin D supplementation in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) in order to reduce the risk of chronic graft-versus-host disease (GVHD), according to a new review article published in Biomedicines.

The authors noted that vitamin D deficiency has become a general global health concern, with as many as 1 in 5 people in India, Pakistan, and Afghanistan reported to be deficient in vitamin D and 13% of people deficient in Europe. However, the deficiency appears to be a particular problem in patients undergoing SCT.

“The incidence of vitamin D deficiency is even higher among patients undergoing allo-HSCT due to long-term hospitalizations or liver or renal toxicities, among other reasons,” they wrote.

Vitamin D is a secosteroid hormone, the authors noted, and it is most notably involved in calcium and phosphate homeostasis in bone formation. Yet, they said it also has other functions, which it carries out primarily by binding to the vitamin D receptor (VDR).

“Through the VDR, vitamin D exerts different functions that influence immune responses, as previously shown in different preclinical models,” the authors noted.

Given the links between vitamin D and the immune system, a number of studies have been undertaken to see whether vitamin D might affect GVHD rates in patients undergoing SCTs. However, the results of those studies have been varied.

In the largest such study, of 492 patients with myeloid malignancies, investigators found vitamin D deficiency was associated with inferior overall survival due to a higher risk of relapse. However, the same study did not find a link between vitamin D deficiency and the overall incidence of acute or chronic GVHD, the authors noted.

In discussing the difficulty in drawing clear conclusions about GVHD and vitamin D deficiency, the authors added that other factors, such as characteristics of the underlying malignancy and patient age, can confound study results. Yet, while the data linking vitamin D deficiency to GvHD incidence were mixed, other studies suggest that the inverse is true, the authors found: Vitamin D supplementation can reduce risk of chronic GVHD.

They examined one of their own trials to see whether individual factors might influence how vitamin D affects rates of chronic GVHD. They found that VDR genotypes made a difference, and they posited a theory as to why supplementation might affect GVHD risk.

“​​Some subtypes of dendritic cells from hosts persist after engraftments; therefore, vitamin D binding to the VDR would inhibit the cells’ differentiation and maturation and would decrease alloreactive T-cell activation at the same time as it would upregulate the tolerogenic properties selectively in myeloid dendritic cells,” they wrote.

In their conclusion, the authors said given vitamin D’s excellent toxicity profile and its apparent efficacy at least on certain cell subsets of the immune system, it makes sense to use vitamin D to reduce chronic GVHD risk in patients undergoing allo-HSCT. However, they said more study is needed to better understand how it works and to discern the best dosing and timing strategies for the intervention.

Reference

Rodríguez-Gil A, Carrillo-Cruz E, Marrero-Cepeda C, Rodríguez G, Pérez-Simón JA. Effect of vitamin D on graft-versus-host disease. Biomedicines. Published online April 24, 2022. doi:10.3390/biomedicines10050987