Vitamin D Deficiency and Survival after Hematopoietic Stem Cell Transplantation

Background:  Vitamin D is involved in calcium and bone homeostasis and has immunomodulatory effects.  Vitamin D deficiency prior to HSCT has been associated with higher risk of chronic GVHD in adults with malignancies.  The significance of vitamin D deficiency on transplant outcomes in pediatric and young adult HSCT patients is not well understood.

Methods:  Serum samples from consecutive HSCT patients prospectively enrolled onto HSCT repository at our institution were tested for 25-hydroxy (25-OH) vitamin D levels  prior to starting HCST (baseline) and at 100 days after transplantation.  A 25-OH vitamin D level of <30 ng/ml was defined as vitamin D deficiency and <20 ng/ml as severe vitamin D deficiency. Continuous and categorical variables were compared using Wilcoxon Rank Sum test and Fisher's exact test, respectively. Survival and cumulative incidence curves were computed using Kaplan Meier and were tested using Log Rank and Gray's test, respectively.

Results:   Pre-transplant (baseline) serum samples were tested for 25-OH Vitamin D level in 135 consecutive HSCT patients; 21 % of whom were already receiving vitamin D supplementation.  Ninety-four of 135 (70%) patients had Vitamin D level <30ng/mL , despite supplemental therapy in 16% of subjects.  Post-transplant serum samples were available  in 129 patients who survived to day 100 post-HSCT. Vitamin D deficiency persisted in 66 of 87 patients (76%) who were already deficient at baseline and survived  to 100 days post-HSCT.  Twenty-four (57%) patients with normal vitamin D levels prior to transplant developed Vitamin D deficiency by 100 days after transplantation. Overall 70% of all patients surviving 100 days after transplantation  had low vitamin D levels,  with the third of them having severe Vitamin D deficiency ( <20ng/ml).  Low vitamin D levels at baseline prior to HSCT were not associated with development of either acute or chronic GVHD (p=0.8), contrary to reports in adults.  However, severe vitamin D deficiency (<20 ng/ml) at 100 days post- HSCT was associated with decreased overall survival after transplantation (p=0.044, Figure).

Conclusions:  Pediatric and young adult patients undergoing HSCT are at high risk for vitamin D deficiency, both before and after HSCT, more so than general population.  This places them at high risk for skeletal and nutritional complications.  Severe vitamin D deficiency at 100 days after-transplantation is associated with worse overall survival and likely represents ongoing chronic illness. Pre-transplant screening and aggressive vitamin D therapy is indicated in these patients to improve long term outcomes after HSCT.