Vitamin D Supplementation Decreases Grade 3-4 Acute Gvhd in Allogeneic Transplants with Normal Baseline Levels

Background: Previous studies have shown that patients receiving AHSCT are likely to have sub-optimal Vit D levels. Vit D has also been shown to have significant immunomodulatory effects, including polarization of T cell population towards Th2 expression and decreasing allogeneic T-cell proliferation while increasing T-reg cell function. Alloreactive T cells upregulate the Vit D receptor and repletion of Vit D in vitro significantly reduces this response. Thus it is hypothesized that patients with VIT D deficiency at onset of AHSCT would have greater incidence and severity of GVHD and that early replacement may lessen the risk of GVHD. In this study we examine this relationship.

Methods: A retrospective evaluation of 290 adult AHSCT at the University of Michigan between January 2007-December 2010. All patients had Serum 25-hydorxyvitamin D (25OHD) levels at admission for AHSCT. Deficient levels were defined to be below 29 ng/ml and normal levels as 30 ng/ml or higher. The incidence and grade of GVHD were defined as maximum overall grade and acute GVHD was defined as starting within the first 100 days. The primary standard GVHD prophylaxis regimens were Tacrolimus/MTX for full intensity and Tacrolimus /MMF for reduced intensity transplants.

Results: Of all AHSCT 77% had Vit D deficiency at onset of transplant with no difference between related donors (RD) and unrelated donors (UD). Vit D supplementation was started within the first week of transplant and occurred in 83% who were Vit D deficient at baseline and 36% of those having normal levels at baseline. In patients with baseline Vit D deficiency there did not appear to be an impact of Vit D supplementation on the incidence of Grade 2-4 GVHD (44% vs 46%) or Grade 3-4 GVHD (17% vs 19%).  However in patients who had baseline Vit D levels of 30 ng/ml or above there was a significant decrease in the incidence of Grade 3-4 GVHD in the group who received Vit D supplementation versus those who did not (9% vs 27%, X²=2.99, p=0.042) and a trend towards a decrease in Grade 2-4 GVHD (35% vs 54%, X²=2.11, p=0.073). This is despite having more Unrelated Donor transplants in the Vit D supplemented group (65% vs 46%).

Conclusion: AHSCT patients have high rates of Vit D deficiency. Ironically this study suggests that Vit D supplementation starting during transplant may significantly decrease the incidence of Grade 3-4 GVHD in patients who have baseline levels >30 ng/ml but not those severely deficient at baseline. This could imply that higher amounts of Vit D supplementation may be required to adequately effect T cell response. Future trials should evaluate the role of increasing Vit D supplementation and determine if an optimal Vit D level  is required to decrease the incidence and severity of acute GVHD.