Ultra-high dose vitamin D in pediatric hematopoietic stem cell transplantation: A nonrandomized controlled trial.

Abstract

BACKGROUND\nVitamin D is essential for bone health and has immunomodulatory properties. Most pediatric patients are vitamin D insufficient (<30ng/mL) prior to hematopoietic stem cell transplantation (HSCT). Standard supplementation strategies fail to achieve vitamin D sufficiency in the acute post-transplant period, and there is scarce data to support optimal vitamin D supplementation in this patient population.\n\n\nOBJECTIVES\nThis study aimed to evaluate whether a single, oral, weight-based ultra-high dose of vitamin D (Stoss dosing) was more effective than standard supplementation to achieve pre-HSCT vitamin D sufficiency and reduce the incidence of HSCT-related complications (acute graft-versus-host disease, veno-occlusive disease, and/or transplant-associated thrombotic microangiopathy) that are associated with immune-mediated endothelial damage. Secondary endpoints examined the immunomodulatory properties of vitamin D.\n\n\nSTUDY DESIGN\nWe conducted a nonrandomized controlled clinical trial of Stoss dosed vitamin D in pediatric patients receiving HSCT. The study prospectively enrolled 33 patients, 29 of whom successfully received Stoss dosed vitamin D and were compared to 136 patients in a historical control. Patient characteristics were compared using Fisher s exact test or t-test. The one-sided Fisher s exact test was utilized for cohort comparison of the primary endpoints. Logistic regression was utilized to examine the association between patient-specific factors and total 25-hydroxy vitamin D (25-OHD) levels and the compiled HSCT complications.\n\n\nRESULTS\nIn the Stoss cohort, 97% (n=28/29) of patients achieved pre-HSCT vitamin D sufficiency compared to 67% (n=10/15) of patients in the historical control who were on standard supplementation at the time the total 25-OHD level was assessed (p=0.013). The mean total 25-OHD level in the Stoss cohort was significantly higher than patients in the historical control who received standard supplementation (72.2ng/ml versus 35.8ng/mL, p<0.001). Nine patients in the Stoss cohort maintained vitamin D sufficiency throughout the first 100 days post HSCT, and the remaining 19 patients maintained sufficiency for a median of 63 days (range 6-105 days) from the Stoss dose. Patients receiving Stoss dosed vitamin D developed a lower combined incidence of HSCT-related complications than the historical control (25% [n=7/28] vs 42% [n=57/136], p=0.055). Following Stoss dosing, immunophenotyping studies found a significant decrease in subsets of CD8+ T cells and mononuclear cells (p=0.040 and 0.013, respectively) and, in a subset of cells, larger decreases in phosphoprotein expression were seen with greater increases in total 25-OHD levels. Inflammatory cytokines did not change significantly following Stoss dosing.\n\n\nCONCLUSIONS\nStoss dosing is therefore a safe and effective approach to maintain vitamin D sufficiency in the immediate post-HSCT period and may be associated with decreased HSCT-related complications. Randomized studies are warranted to further investigate the efficacy of Stoss dosed Vitamin D to improve bone health and reduce complications in pediatric patients receiving HSCT.