Impact of Vitamin D Level After Allogeneic Hematopoietic Stem Cell Transplant

Vitamin D (VD) deficiency can cause osteomalacia, aching bone pain, muscle weakness, fatigue, increase risk of fracture and precipitate or exacerbate osteopenia/osteoporosis. Allogeneic hematopoietic stem cell transplant (HCT) patients are susceptible to low VD level secondary to poor oral intake, decreased exposure to sunlight and treatment related malabsorption. VD level has been correlated to cancer incidence and VD metabolites have been used in the treatment of myeloid leukemia. VD shows promising immunomodulatory properties and correction of low VD level may mitigate manifestations of graft versus host disease (GVHD). Reports have suggested that low VD level appears to increase the incidence of GVHD. We hypothesize that there is a relationship between low VD level and morbidity (specifically incidence of acute GVHD), mortality and relapse incidence after HCT. We therefore studied VD levels pre- and post-HCT to determine if VD level impacts these outcomes.

241 patients underwent myeloblative or non-myeloablative HCT between January 1, 2009 and January 31, 2011 at our institution. Baseline demographic data, disease characteristics, transplant variables and outcomes data were obtained from the transplant database. These data were supplemented by retrospective chart review for pre- and post-transplant VD level. Categories for VD level included normal (>30 ng/ml) or abnormal (<30 ng/ml).

131 (54%) of patients who underwent myeloblative or non-myeloablative HCT had their VD level evaluated either pre-transplant, post-transplant or both. Pre-HCT 57 (56%) patients, 100 days post-HCT 55 (59%) patients and 365 days post-HCT 12 (32%) patients had a low VD level. 51 (38%) of patients had a reduced intensity HCT and 80 patients (62%) had an ablative conditioning regimen. 11 (8.4%) patients had acute GVHD. Comparison of VD level among those with acute GVHD did show a higher incidence of acute GVHD between those with a low or normal VD level (HR=3.14, 95% CI: 0.35–28.33) however this association was not statistically significant (p=0.3079). Survival analysis in those with a low VD level pre-HCT showed there was not a higher risk of mortality (HR=1.14, 95% CI: 0.18–7.38) after adjusting for post- VD level, and this association was not statistically significant (p=0.8921). Survival analysis in those with a low VD level post-HCT did show a higher risk of mortality (HR=2.59, 95% CI: 0.26–25) after adjusting for pre-HCT VD level, however, this association was not statistically significant (p=0.4155). The relationship between VD level and relapse at 1 year post-HCT was not able to be examined because the VD level for patients who relapsed was not available.

Half of patients undergoing HCT had VD testing pre- or post- HCT. Just over half of the patients tested had a low VD level pre- and 100 days post-HCT. It is notable that 365 days post HCT the number of patients with low VD level had decreased. This could be attributable to less time in the hospital thus increasing sun exposure, increasing performance status allowing better ingestion and absorption of VD in the gastrointestinal tract or proper supplementation of a low level noted previously. There was no significant difference in incidence of acute GVHD by VD level though there was a trend for increased risk. Pre- and post-HCT VD level did not significantly impact mortality but there was a trend toward higher risk in those with a low VD level post-HCT. This is the first study, to our knowledge, to evaluate the impact of VD level on mortality post-HCT. Our study confirms that many patients have a low VD level pre-and post-HCT. These findings, especially the trend towards a higher mortality risk and higher incidence of acute GVHD in those who have a low VD level post-HCT, warrant further prospective investigation. VD supplementation may be a low cost, easy to implement addition to routine post HCT care that might reduce HCT associated mortality.

Reeder:Celgene: Research Funding.