Vitamin D Supplementation: Association With Serum Cytokines in Pediatric Hematopoietic Stem Cell Transplantation

Abstract

Vitamin D deficiency is prevalent in pediatric patients presenting for hematopoietic stem cell transplantation (HSCT) and has been linked to poor clinical outcomes. Using the data from a randomized control trial, in this paper we explore the effects of vitamin D supplementation on circulating cytokine levels during pediatric HSCT (www.clinicaltrials.gov as NCT03176849). A total of 41 children, 20 received Stoss therapy and 21 children received standard of care vitamin D supplementation. Levels of 25(OH)D and 20 cytokines were assessed at baseline and day +30. Significantly (P < 0.05) higher levels of mostly proinflammatory cytokines, FGF, GCSF, TNFα, IL-2, IL-6, IP10 were detected pre-transplant for patients with low compared to those with normal vitamin D levels. In sex stratified models that compare changes in cytokines between Stoss vs. standard of care, females in the Stoss group show greater changes in mostly pro -inflammatory cytokines- IP-10 (P = 0.0047), MIG (P = 0.009), and RANTES (P = 0.0047), IL-2R (P = 0.07) and IL-6(P = 0.069). Despite a small sample size, these findings suggest vitamin D deficiency affects the pre-transplant cytokine milieu and higher doses of vitamin D (Stoss therapy) appears to influence proinflammatory cytokine responses in a sex specific manner during pediatric HSCT. Larger clinical trials are warranted to validate these results.

Nutrition management of pediatric patients undergoing hematopoietic stem cell transplantation: Guidelines, gaps, and research

“…Cytokine levels that were significantly lower in high dose groups were IP10, monokine induced by gamma, and regulated upon activation, normal T cell expressed and secreted. 57 Bodea et al 58 assessed Stoss dose treatment in pediatric HSCT patients by randomized control and concluded that at day +30, 25-OHD levels were significantly higher (P = 0.04) in the Stoss cohort compared to the control. Their follow-up study (2022) compared vitamin D status and its impact on early (day +30) post-HSCT outcomes, specifically acute GVHD, immune recovery, infection rates, and survival.…”

“…Findings from this study also suggest that high doses (Stoss dose) of vitamin D diminished proinflammatory cytokine responses post‐HSCT. Cytokine levels that were significantly lower in high dose groups were IP10, monokine induced by gamma, and regulated upon activation, normal T cell expressed and secreted 57 . Bodea et al 58 assessed Stoss dose treatment in pediatric HSCT patients by randomized control and concluded that at day +30, 25‐OHD levels were significantly higher ( P = 0.04) in the Stoss cohort compared to the control.…”

Optimized vitamin D repletion with oral thin film cholecalciferol in patients undergoing stem cell transplant

“… 7 Perhaps even more worrisome is that the vitamin D deficiency uncovered in this vulnerable population was persistent and associated with decreased overall survival. 7 , 8 , 9 , 10 , 11 Compared with deficient vitamin D levels, normal vitamin D levels before transplant and in the early posttransplant period have been associated with a lower incidence of graft-versus-host disease (GVHD), lower levels of proinflammatory cytokines, and improved immune reconstitution. 11 , 12 , 13 With aggressive enteral supplementation, we have been able to significantly improve outcomes and quality of life for many of these children.…”