Vitamin A Supplementation Could Improve Transplant Outcomes

Author’s Perspective

Co-author Stella Davies, MBBS, PhD, MRCP: “Vitamin A is an important regulator of immunity, and higher levels seem to be beneficial [in this patient population]. We are doing a pilot study to test whether a large dose of vitamin A before transplantation might reduce gut graft-versus-host disease and blood stream infections.”

In an article published in Blood, researchers evaluated the effects of vitamin A on the incidence of graft-versus-host disease (GVHD), a major cause of non-relapse morbidity and mortality following hematopoietic cell transplantation (HCT), based on the nutrient’s ability to increase intestinal permeability.

The authors, led by Dana T. Lounder, MD, from the Division of Bone Marrow Transplant and Immune Deficiency at the Cincinnati Children’s Hospital Medical Center in Ohio, assessed 114 consecutive patients (median age = 8 years; range = 0.4-32 years) enrolled in a prospective cohort study and undergoing allogenic HCT at their institution’s BMT repository. Patients had bone marrow failure (n=47; 38%), immune deficiency (n=44; 36%), or malignancy (n=33; 26%) and were being treated with myeloablative (n=72; 58%) or reduced-intensity (n=52; 42%) conditioning regimens.

The median vitamin A level at 30 days post-transplant was 1.30 ng/mL (range = 1.0-1.7 ng/mL). Vitamin D levels did not appear to be correlated with vitamin A levels (p=0.18), thus “levels of vitamin A were independent of nutritional status,” the authors noted.

The overall incidence of grade 2-4 GVHD was 32.2 percent (n=40); 25 percent of patients experienced gastrointestinal (GI) GVHD (n=31) after a median onset of 38 days (range = 15-261 days).

The cumulative incidence of grade 2-4 GVHD was significantly higher in children with vitamin A levels below the median (<1.30 ng/mL; 38.6%), compared to those with levels above the median (>1.30 ng/mL; 12.4%) at 100 days post-transplant (p=0.0008).

Similarly, the rate of GI GVHD was greater in patients with vitamin A levels below the median (30.4% vs. 7% at 100 days; p=0.002), as was the cumulative incidence of stage 3/4 GI GVHD (23% vs. 7% at 100 days; p=0.03).

See TABLE for results from the multivariate analysis of GVHD and treatment-related mortality risk in this patient population.

Bloodstream infections at one year also increased in patients with lower vitamin A levels (24% vs. 8%; p=0.03), which “supports our hypothesis of increased intestinal permeability,” the authors wrote. In addition, expression of CCR9 on T-effector memory cells at 30 days post-transplant was increased in children with vitamin A levels below the median (p=0.03).

“Taken together, these data support our hypothesis that low levels of vitamin A actively promote GI GVHD,” the authors concluded. “Vitamin A supplementation might improve transplant outcomes.”

The study is limited in that the patient population was largely comprised of pediatric patients who were receiving transplant for non-malignant disorders, which may not translate to the adult population in which the majority of transplants are performed to treat cancer.

Source: Lounder DT, Khandelwal P, Dandoy C, et al. Lower levels of vitamin A are associated with increased gastrointestinal graft versus host disease in children. Blood. 2017 March 9. [Epub ahead of print]

TABLE. Multivariate Analysis of Development of GVHD and TRM
  GVHD

Odds ratio

p Value TRM

Odds ratio

p Value
Vitamin A level 3.32

(95% CI 1.5-6.7)

0.003 3.07

(95% CI 0.9-10.1)

0.06
Malignancy 1.9

(95% CI 1.0-3.7)

0.06 1.89

(95% CI 0.6-5.6)

0.27
HLA match 1.42

(95% CI 0.5-3.9)

0.50 1.11

(95% CI 0.2-6.7)

0.90
Stem cell source
   BM 1.8

(95% CI 0.5-6.0)

0.3 1.74

(95% CI 0.2-13.7)

0.6
   UCB 1.7

(95% CI 0.1-24.2)

0.7 3.73

(95% CI 0.08-165.9)

0.5
   PBSC N/A N/A N/A N/A
GVHD = graft-versus-host disease; TRM = transplant-related mortality; OR = odds ratio; HLA = human leukocyte antigen; BM = bone marrow; UCB = umbilical cord blood; PBSC = peripheral blood stem cell; N/A = not available

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