Vitamin D Deficiency in Pediatric Hematopoietic Stem Cell Transplantation Patients Despite Both Standard and Aggressive Supplementation

Abstract

We recently reported that more than 70% of pediatric and young adult patients had a vitamin D (VD) deficiency at the time of their hematopoietic stem cell transplantation (HSCT). Moreover, VD deficiency was associated with inferior survival at 100 days after transplantation. The goal of the present study was to evaluate the VD requirements needed to maintain an optimal VD level (30 to 60 ng/mL) during the first 3 months after transplantation using real-time VD monitoring and personalized VD supplementation. We examined 2 cohorts in this study: cohort 1, the “preintervention” cohort (n = 35), who were treated according to National Kidney Foundation guidelines for VD therapy, and cohort 2, the “intervention” cohort (n = 25) who were treated with high-dose VD with an aggressive dosage increase in those who remained VD-insufficient. Results from cohort 1 showed that despite aggressive monitoring and VD supplementation, therapeutic vitamin D levels were difficult to achieve and maintain in HSCT recipients during the early post-transplantation period. Only 43% of cohort 1 achieved a therapeutic VD level, leading to our intervention in cohort 2. Outcomes improved in cohort 2, but still only 64% of cohort 2 patients achieved a therapeutic VD level despite receiving >200 IU/kg/day of VD enterally. The median VD level in patients who did achieve sufficient levels was 40 ng/mL, with only 1 patient in each cohort achieving a supratherapeutic but nontoxic level. These data indicate that standard guidelines for VD replacement are inadequate in HSCT recipients, and further work is needed to define more appropriate dosing in this clinical setting.

Vitamin D deficiency and outcomes in pediatric hematopoietic stem cell transplantation

“…Despite high levels of year‐round sunlight, a high prevalence of suboptimal vitamin D levels (56%) was detected in children presenting for HSCT at our institution (Phoenix, AZ 33°N latitude). This finding further extends previous pediatric reports that the majority of pediatric patients have suboptimal vitamin D levels at time of HSCT 17–22 . Our data also showed an association between very low (<20 ng/ml) levels of vitamin D and reduced survival (see Fig.…”

“…Wallace et al. recently reported that despite giving a much higher than recommended vitamin D dose, more than 50% of their patients remained deficient …”

“…Despite growing numbers of publications describing the effects of vitamin D in adult HSCT patients and its impact on GVHD and infection rates, few publications describe the prevalence of vitamin D and its effect on clinical outcomes in pediatric HSCT . These studies report prevalence of low vitamin D levels pre‐HSCT ranging from 23 to 70% with varying survival outcomes in this population.…”

“…14,15 Some individuals develop altered gastrointestinal absorptive capacity following HSCT as a result of gastrointestinal GVHD, intestinal bile-salt deficiency, pancreatic enzyme insufficiency, and/or bacterial overgrowth. Consequently, these individuals have difficulty absorbing dietary fat and fat-soluble vitamins such as vitamin D. 16 Despite growing numbers of publications describing the effects of vitamin D in adult HSCT patients and its impact on GVHD and infection rates, few publications describe the prevalence of vitamin D and its effect on clinical outcomes in pediatric HSCT. [17][18][19][20][21][22] These studies report prevalence of low vitamin D levels pre-HSCT ranging from 23 to 70% with varying survival outcomes in this population. The aim of this study is to describe the prevalence of suboptimal vitamin D levels in our pediatric patients undergoing allogenic HSCT and its association with 1-year overall survival.…”

Healthcare Burden, Risk Factors, and Outcomes of Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infections after Stem Cell Transplantation

“…The frequency of TA-TMA (and perhaps MBI-LCBI) in high-risk patients could be reduced by use of alternative transplant regimes (eg, reduced use of sirolimus and calcineurin inhibitors) or careful screening for TA-TMA and early institution of complement blockade [23]. In alternative strategies, we are currently studying dietary approaches to improve gut permeability and reduce MBI-LCBIs, including vitamins A and D, use of nondigestible oligosaccharides to maintain bowel microbiome diversity, and human behavior strategies to improve compliance with mouth care, another potential site of translocation [24,25]. …”