Vitamin D, an essential hormone with function ranging from mediating bone hemostasis to immune modulation, has been reported to be deficient in the majority of myeloablative allogeneic hematopoietic cell transplant (HCT) recipients and associated with diagnosis of chronic graft versus host disease (GVHD). There are two types of GVHD (acute and chronic) which carries a high mortality rate of 34% (Grade II-IV).
Current studies continue to support the finding that there is a high prevalence of vitamin D deficiency within HCT recipients. Rosenblatt et al  has shown vitamin D deficiency may increase the risk of acute GVHD due to the loss of known immunomodulatory effects of vitamin D. Ganetsky  reported that vitamin D deficiency measured at 30 days post-HCT was associated with increased risk of grade II-IV cutaneous acute GVHD (p=0.05). Ganetsky proposed that vitamin D might confer a protective effect against cutaneous acute GVHD via reduction in CCR4 expression. The concept of a protective effect may be best illustrated by Glotzbeker  who reported an incidence of chronic GVHD of 63.8% at two years post transplant in HCT recipients with a vitamin D level <25ng/ml, compared to an incidence of 23.8% in recipients with higher vitamin D levels (>25ng/ml, p= 0.009).
We tested the hypothesis that vitamin D deficiency is associated with acute GVHD within 90 days after HCT.
Fifty consecutive allogeneic recipients were selected from the HCT database based on blood samples available pre-transplant, 30 days, and 90 days post HCT over two years. To gauge the impact of vitamin D levels in the HCT, we assessed vitamin D levels at three time points, pre-transplant, day +30 and day +90, for a total of 150 samples. The bio-samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for 25-OH vitamin D (D2, D3 and total). For analytical purposes vitamin D deficiency was defined as a vitamin D 25-OH level of less than 25 ng/ml. Clinical data was abstracted from the medical record with acute GVHD scoring system (already completed in patient records).
Of the 50 patients, 74% had vitamin D deficiency (median 20±8 ng/ml) pre-HCT, 86% had vitamin D deficiency at 30 days (median 16±8 ng/ml, p=.048), and remained vitamin D deficient at 90 days post HCT (median 16±10 ng/ml). Thirty percent of these 50 patients were diagnosed with Grade II-IV acute GVHD by 90 days post transplant. All patients with grade II-IV acute GVHD by 90 days had vitamin D deficiency (median 12±6 ng/ml, range 5-23ng/ml, p=.08).
Given our findings as well as other recent research, it has compelled our Blood and Marrow Transplant (BMT) program to adopt a standard of care for monitoring and supplementing vitamin D. In developing our standard of care, we polled six BMT Centers across the US to identify their practice for monitoring and supplementing vitamin D. We learned that although many BMT centers were supplementing their patients, there were widely varying protocols among the centers. The frequency of vitamin D level checks were often inconsistent and the dosing for supplementation covered a wide range, and limited follow-up was reported. Implementation of the standard of care involved multiple forms of communication such as faculty meetings and updates, RN, APP and fellow in-services, RN coordinator meetings, newsletters, MD guidebook update, EPIC charting templates and smart phrases, communication between inpatient and outpatient teams, inclusion in pre and post transplant letter to referring MD. A vitamin D EPIC report was also developed to assess compliance outcomes and data analysis of adequate dosing.
Our implementation of the standard of care for monitoring and supplementing vitamin D occurred 18 months ago. We will continue to collect the data for two years to evaluate the impact of adequate vitamin D levels and its potential buffering of acute GVHD. Our hypothesis is that this new data will provide the needed evidence to elucidate the benefits of adequate vitamin D levels for the allogeneic HCT recipient population.
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