Vitamin A supplementation may improve outcomes after pediatric bone marrow transplant

Lower levels of vitamin A promoted gastrointestinal graft-versus-host disease in children following hematopoietic stem cell transplant, according to results of a prospective cohort study.

Thus, vitamin A supplementation may improve transplant outcomes for these patients, according to the researchers.

“We found that patients with vitamin A levels below the median at day 30 posttransplant had an increased incidence of [gastrointestinal graft-versus-host disease (GVHD)] and transplant-related mortality compared with those with vitamin A levels above the median,” Dana T. Lounder, MD, from the division of bone marrow transplant and immune deficiency at Cincinnati Children's Hospital Medical Center, and colleagues wrote. “Importantly, we found a normal distribution of vitamin A levels, so our findings likely reflect normal variation in physiologic activity of vitamin A, rather than a large group of outliers with pathological vitamin A deficiency.”

Researchers seek to identify pretransplant host factors that could be addressed prior to transplant to reduce risk for GVHD. Vitamin A is a candidate variable because it modifies gut permeability, is needed for mucosal tolerance and regulates lymphocyte trafficking to the gut.

Lounder and colleagues hypothesized that increased levels of vitamin A would reduce the risk for GVHD — including gastrointestinal GVHD — by improving intestinal permeability, increasing secretion of IL-22, and reducing mucosal injury and lymphocyte homing to the gut.

The researchers enrolled 114 consecutive patients (median age, 8 years; range 0.4-32) undergoing allogeneic HSCT at Cincinnati Children’s Hospital Medical Center. Indication for transplant included malignancy (26%), immune deficiency (36%) and bone marrow failure (38%). Most patients (84%) received bone marrow as their cell source.

Researchers collected blood samples and clinical data once a week from admission until 100 days posttransplant. They used the Human Vitamin A ELISA kit (MyBioSource) to measure free vitamin A levels in patient plasma at 30 days posttransplant.

Researchers reported a median vitamin A level of 1.3 ng/mL (range, 1-1.7) at 30 days posttransplant.

Overall, 40 patients (32.2%) experienced grade 2 to grade 4 GVHD and 31 (25%) had gastrointestinal GVHD after a median onset of 38 days (range, 15-261).

At 100 days, grade 2 to grade 4 GVHD occurred more frequently among patients with vitamin A levels below the median than among patients who had vitamin A levels above the median (38.6% vs. 12.4%; P = .0008). Patients with lower vitamin A levels also demonstrated higher rates of gastrointestinal GVHD (30.4% vs. 7%; P = .002).

At 1 year, patients with vitamin A levels below the median demonstrated higher rates of treatment-related mortality (17.7% vs 7.4%; P = .03) and blood stream infections (24% vs 8%; P = .03).

Multivariate analyses adjusted for diagnosis, stem cell source and HLA match showed low vitamin A level remained an independent risk factor for GVHD (OR = 3.3; P = .003) and transplant-related mortality (OR = 3.07; P = .06).

Incidence of mucosal barrier injury–laboratory confirmed bloodstream infections — measured to determine intestinal permeability — appeared higher in children with vitamin A levels below the median at 1 year (24% vs. 8%; P = .03), supporting the researchers’ hypothesis of increased intestinal permeability.

Serum levels of intestinal fatty acid binding protein decreased after transplant, which confirmed the presence of mucosal injury. However, levels of this protein did not correlate with vitamin A levels, indicating that vitamin A did not protect against mucosal injury.

Expression of CCR9 — a gut-homing receptor — on T-effector memory cells 30 days after transplant appeared higher in children with vitamin A levels below the median (r = –0.34; P = .03).

“Taken together, these data support our hypothesis that low levels of vitamin A actively promote gastrointestinal GVHD, and are not simply a marker of poor nutritional status or a sicker patient,” the researchers wrote. – by Melinda Stevens

Disclosure : The researchers report no relevant financial disclosures.