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

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.

Impact of Adequate Day 30 Post-Pediatric Hematopoietic Stem Cell Transplantation Vitamin D Level on Clinical Outcome: An Observational Cohort Study.

This prospective observational study evaluated the impact of adequate vitamin D levels by day +30 after vitamin D supplementation on early post-HSCT outcomes, including acute graft-versus-host disease (aGVHD), immune recovery, infection rates, and overall survival. Forty children (age 2 to 16 years) undergoing hematopoietic stem cell transplantation (HSCT) were given vitamin D supplementation, were followed prospectively from day +30 post-transplantation, and had day +30 vitamin D levels measured. Thirty patients with normal vitamin D levels (≥30 ng/mL) were compared with 10 patients with low day +30 vitamin D levels (<30 ng/mL). The times to neutrophil and platelet engraftment was similar in both day +30 vitamin D groups (P = .13 and .32, respectively). At day +100, slower immune recovery in CD4+ cells (P = .027), CD19+ cells (P = .024), and natural killer cells (P = .042) was observed in the patients with a low vitamin D level (<30 ng/mL), and no between-group differences were detected in the incidence of infection (P = .72) or grade II-IV aGVHD (P = .46). Our findings show that patients with adequate vitamin D levels during transplantation had faster immune recovery and better overall survival. Vitamin D deficiency does not appear to impact engraftment or the risk of aGVHD and infection in pediatric HSCT.

Stoss therapy is safe for treatment of vitamin D deficiency in pediatric patients undergoing HSCT.

Vitamin D deficiency remains common among pediatric patients undergoing hematopoietic stem cell transplant (HSCT) despite both aggressive and standard of care strategies. This study examined the safety and efficacy of single high-dose oral vitamin D therapy (Stoss therapy) for treatment of vitamin D deficiency in HSCT recipients. Patients ages 1-21 years presenting for HSCT were randomized to receive either Stoss regimen plus weekly/daily supplementation or standard of care, per US Endocrine Society guidelines. Among the total 48 subjects, 22 (46%) were randomized to Stoss and 26 (54%) to control arms. Baseline 25-hydroxyvitamin D (25-OHD) levels were insufficient/deficient in total of 34 (71%) patients, without difference between treatment groups. The Stoss regimen was well tolerated and no toxicity was observed. At Day +30, mean 25-OHD levels were significantly higher (P = 0.04) with Stoss (42.3 ± 12 µg/l) compared to controls (35.6 ± 14.3 µg/l), and a higher proportion of Stoss patients had adequate vitamin D levels than controls (85% vs 65%). Stoss therapy is a safe and efficacious treatment option for vitamin D deficiency in children undergoing HSCT and may achieve sufficient levels more rapidly than standard of care. This trial was registered at www.clinicaltrials.gov as NCT03176849.

Successful treatment of severe refractory autoimmune hemolytic anemia after hematopoietic stem cell transplant with abatacept.

BACKGROUND: After hematopoietic stem cell transplantation (HSCT) autoimmune hemolytic anemia (AIHA) is a known and fairly common complication. It is often refractory to conventional therapies including corticosteroids, intravenous immunoglobulin, splenectomy, and the more recently described use of monoclonal antibodies. The high morbidity associated with these severe persistent cases elucidates the gaps in alternative therapies available for treatment. STUDY DESIGN AND METHODS: We described the successful use of abatacept for severe refractory AIHA after HSCT in three patients. RESULTS: Three pediatric patients with refractory AIHA after allogeneic stem cell transplantation were observed to be unresponsive to multitude immunosuppressive therapies, resulting in persistent transfusion dependency. Treatment with abatacept, a fusion protein that inhibits T-cell activation by binding to CD80/CD86 on antigen-presenting cells (APCs), thus blocking the required CD28 interaction between APCs and T cells, resulted in the resolution of hemolysis. CONCLUSION: Abatacept may provide significant clinical benefit in the management of AIHA after HSCT.

Vitamin D deficiency and outcomes in pediatric hematopoietic stem cell transplantation.

BACKGROUND: Pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) are frequently diagnosed with vitamin D deficiency, which may impact outcomes. OBJECTIVES: To estimate the prevalence of vitamin D deficiency and examine its association with short-term survival in pediatric HSCT patients. METHODS: Patients undergoing HSCT at Phoenix Children's Hospital were retrospectively identified. Routine serum 25-hydroxyvitamin D measurements were described prior to transplant and at 100 days and 1-year post-HSCT. Associations of pre-HSCT vitamin D groups (i.e., normal ≥30 ng/ml, insufficient 20-29 ng/ml, and deficient <30 ng/ml) with demographics, clinical factors, and outcomes were examined using nonparametric tests and Cox proportional hazards analyses. RESULTS: Among 72 study subjects, the median vitamin D pre-HSCT was 26 ng/ml (range: 19-34 ng/ml). Levels were insufficient and deficient in 25 (35%) and 20 (28%) patients, respectively, with only two (3%) patients on supplemental therapy pre-HSCT. Despite supplemental therapy provided to 46 (74%) subjects, insufficient/deficient rates did not significantly change between pre-HSCT and 100 days post-HSCT, but mean vitamin D levels significantly increased by 1-year post-HSCT (P = 0.01).Vitamin D pre-HSCT was not associated with the development of acute or chronic graft-versus-host disease (GVHD) or delayed engraftment. Overall 1-year survival was significantly lower for patients with deficient (65%) compared to normal (93%) pre-HSCT vitamin D (P = 0.001). CONCLUSION: Suboptimal vitamin D levels are common in pediatric patients scheduled to receive HSCT and are associated with lower overall 1-year survival. Further study is warranted to delineate the mechanisms underlying the role of vitamin D in successful HSCT.