Effect of Vitamin D on Graft-versus-Host Disease

Abstract

The different cell subsets of the immune system express the vitamin D receptor (VDR). Through the VDR, vitamin D exerts different functions that influence immune responses, as previously shown in different preclinical models. Based on this background, retrospective studies explored the impacts of vitamin D levels on the outcomes of patients undergoing allogeneic hematopoietic stem-cell transplantation, showing that vitamin D deficiency is related to an increased risk of complications, especially graft-versus-host disease. These results were confirmed in a prospective cohort trial, although further studies are required to confirm this data. In addition, the role of vitamin D on the treatment of hematologic malignancies was also explored. Considering this dual effect on both the immune systems and tumor cells of patients with hematologic malignancies, vitamin D might be useful in this setting to decrease both graft-versus-host disease and relapse rates.

Pre‐transplantation vitamin D deficiency increases acute graft‐versus‐host disease after hematopoietic stem cell transplantation in thalassemia major patients

“…Despite conflicting results, pediatric studies often report that VDD is not associated with aGVHD, rather related with cGVHD and low survival rates 3,4,18 a statement with which the findings of this study conflict: where only one patient died (Table 1) and no association was found with cGVHD. One plausible explanation for this difference can be that all other studies 3,6,8,12,17 included patients with various malignant and non‐malignant conditions with different baseline problems such as leukemias and immunodeficiencies prior to HSCT.…”

“…As all our patients received vitamin D supplementation and the fact that low vitamin D 3 of the patients improved in the 3rd month after HSCT supports that vitamin D supplementation may have protective effect against cGVHD. Furthermore, in HSCTs with peripheral blood stem cell (PBSC) sources in patients with VDD, we observed aGVHD more frequently than in HSCTs with other sources which may possibly be explained by the absence of antiproliferative effect of vitamin D 3 on peripheral blood lymphocytes 3,22,23 in the early stages after HSCT. The reason why this association was not observed in other studies needs to be investigated comprehensively if this issue is only related with TM patients who have additional hormonal problems described above.…”

“…Evidence of an inverse association between vitamin D 3 and the development of several autoimmune diseases demonstrates the importance of the immunomodulatory characteristics of vitamin D 3 2 . Although there are many studies on the efficacy of vitamin D deficiency (VDD) in hematopoetic stem cell transplantation (HSCT) where immunomodulation is very important, outcomes have often reported conflicting results 3–6 . As graft‐versus‐host disease (GVHD) has similarities with autoimmune diseases, GVHD is one of the most striking issue in these studies with regards to the frequency of GVHD in patients with VDD prior to HSCT 3 .…”

“…Although there are many studies on the efficacy of vitamin D deficiency (VDD) in hematopoetic stem cell transplantation (HSCT) where immunomodulation is very important, outcomes have often reported conflicting results 3–6 . As graft‐versus‐host disease (GVHD) has similarities with autoimmune diseases, GVHD is one of the most striking issue in these studies with regards to the frequency of GVHD in patients with VDD prior to HSCT 3 . While some studies have shown a higher incidence of GVHD in patients with VDD, other studies have shown no such correlation 4,7–9 …”

“…[3][4][5][6] As graft-versushost disease (GVHD) has similarities with autoimmune diseases, GVHD is one of the most striking issue in these studies with regards to the frequency of GVHD in patients with VDD prior to HSCT. 3 While some studies have shown a higher incidence of GVHD in patients with VDD, other studies have shown no such correlation. 4,[7][8][9] One of the likely explanations as to why the reports of HSCT outcomes related to VDD were not correlated is that the patient populations included in these studies were not homogenous.…”