A Single Ultra High Dose of Vitamin D is Safe and Feasible in Early Peri-Transplant Period to Prevent Vitamin D Deficiency in Pediatric HSCT Recipients

Background: Vitamin D (VD) deficiency is associated with inferior transplant survival at 100 days after transplantation. We have previously reported that 70% of pediatric and young adult patients are VD deficient at the time of hematopoietic stem cell transplant (HSCT). Achieving and maintaining therapeutic VD levels in HSCT recipients is extremely challenging, and requires as much as 200 IU/kg/day of VD to sustain adequate VD levels in the first 3-6 months after transplant (Wallace et al., BBMT 2016). Poor compliance in the setting of mucositis, and concomitant use of critical transplant drugs that interfere with VD absorption compound this challenge. The purpose of this prospective study was to evaluate the safety and efficacy of a single ultra-high dose (UHD) of VD prior to starting transplant. Methods: Ten consecutive HSCT recipients with a pre-transplant 25-OH VD level of <50 ng/mL were enrolled onto this study. A single oral UHD VD dose was administered based on patient weight and pre- transplant VD level prior to Day 0 (Figure 1). Peak blood VD level was defined as 2 consecutive levels in plateau or maximum level followed by subsequent decrease in measureable 25-OH VD. VD level of 30-150 ng/mL was counted as therapeutic. All patients received close monitoring of 25-OH VD levels, calcium, phosphate, PTH, urine calcium/creatinine ratio and n-telopeptide for safety assessment. Study subjects were monitored for 19 weeks. Number of days when therapeutic VD level was sustained after single VD dose was documented for each study subject. Results: Study subjects were an average of 6.6 years of age (range .75-17 years). Median pre-transplant 25-OH VD level was 27 (range 6.9-47.8). All patients were able to tolerate a single oral UHD of VD administration under direct medical supervision. No other oral VD supplements were administered. Three of 10 patients received 400 IU/day of VD in parenteral nutrition for 5 days only during the study window. All study patients achieved our therapeutic VD goal of >30 ng/mL and sustained a therapeutic VD level for a median of 9 weeks (range 6-19 weeks). A median peak VD level of 88 ng/ml (range 44-138 n/ml) was achieved a median 9 days (range 4-15 days) after single UHD VD dose. There were no electrolyte abnormalities attributed to the UHD VD. Seven of ten patients had elevated urine calcium/creatinine ratios during treatment, but none showed clinical signs of nephrocalcinosis or nephrolithiasis. Concluson: A single oral ultra-high dose VD treatment given prior to HSCT is safe and well tolerated in children. Patients in our study were able to achieve and sustain therapeutic VD levels through the critical and challenging window of time during which VD sufficiency may contribute to improved overall survival. Larger prospective studies are needed to address the impact of single ultra-high dose VD treatment on HSCT outcomes.