Pre‐transplantation vitamin D deficiency increases acute graft‐versus‐host disease after hematopoietic stem cell transplantation in thalassemia major patients

Abstract

Background: Although there are many studies on the role of vitamin D deficiency (VDD) in hematopoetic stem cell transplantation (HSCT), outcomes have often reported conflicting results because of the heterogeneity of the patients in the studies. Methods:We investigated the association between VDD prior to HSCT and outcomes after HSCT in a relatively homogenous group of patients with thalassemia major (TM) who received identical treatment for TM before transplantation, and the same conditioning regimen and GVHD prophylaxis during and after transplantation. All patients, including the patients with normal vitamin D 3 levels received 400 to 800 IU per day of vitamin D for the first 6 months after HSCT.Results: Pre-HSCT VDD increased the frequency of aGVHD after transplantation, particularly in HSCTs performed with PBSC for the stem cell source. Pre-transplant low vitamin D 3 levels had no association with transplant outcomes such as engraftment, viral infections, alloimmunization, chronic GvHD, total days of hospitalization, and success in terms of transfusion independence.Conclusions: Low vitamin D 3 levels before HSCT carry a significant risk for aGVHD. All patients with TM should be screened for VDD before HSCT, and every effort should be made to supplement vitamin D before the transplant in VDD patients.

Nutritional Support Best Practices in Pediatric Blood and Marrow Transplant Patients: An Integrative Review

“…The gut microbiome is also understood to play a role in patient outcomes; lack of a stimulated and diverse microbiome, such as that observed with the exclusive use of PN, could contribute to increased rates of GVHD and infections [ 22 , 44 , 50 ]. Vitamin D is also thought to play a role in immunoregulation and gut inflammation, with several adult and pediatric studies showing increased rates of acute and chronic GVHD in patients with documented vitamin D deficiency [ 56 , 57 ].…”

Nutritional interventions in patients with graft-versus-host disease

“…Vitamin D's role in GvHD has been widely documented in the last two years and may play a key role in GvHD pathogenesis: a clinical study demonstrated that a low vitamin D3 level, defined as a level below 20 ng/ml before allo-HCT, was associated with a higher incidence of GvHD in a pediatric cohort suffering from thalassemia major undergoing allo-HCT ( N = 100) [31 ▪ ]. Another study found that a pediatric cohort treated with ultra-high vitamin D supplementation had a lower GvHD incidence [32].…”

The Promise of Precision Nutrition for Modulation of the Gut Microbiota as a Novel Therapeutic Approach to Acute Graft-versus-host Disease

“…117 Pretransplant vitamin D deficiency and the expression of the vitamin D receptor (VDR) were also associated with a higher risk of aGVHD. 118,119 Multiple interventional trials supplementing vitamin D before and after the transplant showed a general improvement in HSCT outcomes [120][121][122][123] with some differences according to the VDR genotypes. 124,125 The modulatory effect of vitamin D supplementation on the gut microbiota has been investigated in other medical conditions, showing a strong effect, particularly on the phyla Bacteroides and Firmicutes, as summarized in a recent systematic review.…”

“…Vitamin D HSCT outcomes improvements, [120][121][122][123] according to VDR genotype 124,125 Higher GVHD risk in vitamin D-deficient patients. 118,119 Vitamin D supplementation before and after the transplant reduces cGVHD incidence 123 NA Human studies, 118,120,125 not randomized clinical trials Meta-analysis of human studies 18 ; RCTs 153,154 18,153,154 Obesity Contrasting data: increased mortality and infections 15,21,27 ; no increased OS and infections [24][25][26]28 Contrasting data: increased risk of GVHD 15,27 ; no changes in GVHD risk 24,25 Reduction of microbial diversity; increased abundance of Akkermansia muciniphila and Enterococcus and reduction of Clostridiaceae family 22,23 Human 15,21,[24][25][26][27][28] and animal studies 22,23 15,21-28 aGVHD, acute graft-vs-host disease; aHSCT, allogeneic hematopoietic stem cell transplantation; EN, enteral nutrition; FOS, fructo-oligosaccharides; GFO, glutamine, fiber, and oligosaccharides; GOS, galacto-oligosaccharade; GVHD, graft-vs-host disease; HSCT, hematopoietic stem cell transplantation; NA, not available; OS, overall survival; PE-EVOO, polyphenolic extracts in extra virgin olive oil; PN, parenteral nutrition; RCT, randomized controlled trial; RS, resistant starch; SCFA, short-chain fatty acid; TMAO, trimethylamine-N-oxide; VDR, vitamin D receptor.…”