Mixed Evidence on the Role of Vitamin D in Hematopoietic Stem Cell Transplantation
Recent research suggests that vitamin D deficiency may negatively influence outcomes after hematopoietic stem cell transplantation.
Vitamin D plays an important role in supporting the growth and maintenance of the skeleton. Recent research suggests a beneficial link between vitamin D and other nonskeletal health outcomes, including immune function, cardiovascular health, and cancer. There is also increasing evidence that vitamin D has immunoregulatory properties and may play a role in the course and outcome of patients who undergo hematopoietic stem cell transplantation (HSCT).
Now a standard therapeutic modality for a number of malignant, hematologic, immunologic, and genetic diseases, HSCT can often improve survival outcomes and may sometimes be the only curative treatment available. Patients undergoing HSCT receive an intravenous infusion of hematopoietic progenitor cells after myeloablative preparation to reestablish marrow function. The success of this procedure is dependent on a variety of factors. Because patients may be nutritionally compromised and may have experienced long periods of hospitalization or lack of sun exposure in general, vitamin D deficiency has been explored as an easily correctable risk factor.
However, the evidence regarding the role of vitamin D in HSCT is decidedly mixed. In a review article published in Bone Marrow Transplantation, Jose Ros-Soto, MD, of the Anthony Nolan Research Institute in the United Kingdom, and colleagues evaluated the current literature regarding the role of vitamin D and its deficiency in relation to immunity for both allogeneic and autologous HSCT.
First discovered in 1919, vitamin D and its relationship to the immune system have been extensively studied. Vitamin D is a steroid hormone that is synthesized in the skin and undergoes 2 consecutive hydroxylations to become fully activated. It exerts its biological function via the vitamin D receptor, which in turn enables the transcription of speciﬁc genes. The authors noted that patients may be at risk for vitamin D deficiency after undergoing HSCT due to factors such as decreased skin synthesis, decreased oral intake or impaired absorption, and altered metabolism of vitamin D.
The current deﬁnition of vitamin D deﬁciency is based on the patient's level of 25(OH)D3, which is the main circulating metabolite of vitamin D in serum. The cutoff value for vitamin D deﬁciency in the general population has not been unanimously agreed upon, although the Endocrine Society Task Force on Vitamin D in the UK and the US Institute of Medicine identify vitamin D deﬁciency as a 25(OH)D level of 50 nmol/L serum.
Definitively linking vitamin D levels to complications following HSCT has been difficult due to the heterogeneity in studies on this topic. The threshold for deficiency varies considerably across studies, and although most do consider 20 ng/mL (50 nmol/L) to be the most reliable cutoff, other values such as 10 ng/mL and 30 ng/mL (25 and 75 nmol/L, respectively) have also been considered. Research focused on this topic is limited and primarily addresses allogeneic HSCT; only 2 of the studies reviewed in this article included some patients who underwent autologous HSCT. Even though most studies agree that 1,25(OH)2D3 activity declines after HSCT, 1 prospective study including 102 adults did not show any signiﬁcant difference in vitamin D serostatus before and after allogeneic HSCT.
When looking at outcomes after HSCT and the relationship to vitamin D serostatus, studies again had mixed results. One retrospective study in 166 adults found that 2 year overall survival was 13% lower in patients with vitamin D deﬁciency. Similarly, a prospective study with 123 pediatric patients found lower overall survival and higher relapse rates in patients with lower 25(OH)D3 levels prior to HSCT. Another study found that vitamin D supplementation enhanced bone marrow recovery by 34%, and CD34+ umbilical cord cells treated with 1,25(OH)2D3 showed longer survival, proliferation, and maturation. Conversely, the authors pointed out that other papers have failed to demonstrate any association between vitamin D status and overall survival, progression-free survival, 2 year disease-free survival, or relapse rate.