医学
安慰剂
移植物抗宿主病
内科学
胃肠病学
维生素
临床终点
无症状的
入射(几何)
造血干细胞移植
累积发病率
移植
免疫学
随机对照试验
外科
病理
替代医学
物理
光学
作者
Pooja Khandelwal,Lucille Langenberg,Nathan Luebbering,Kelly E. Lake,Abigail Butcher,Kylie Bota,Kristie N. Ramos,Cynthia B. Taggart,Hannah Choe,Sumithira Vasu,Ashley Teusink‐Cross,Jane Koo,Gregory L. Wallace,Lindsey E. Romick-Rosendale,Miki Watanabe‐Chailland,David Haslam,Adam Lane,Stella M. Davies
出处
期刊:Blood
[American Society of Hematology]
日期:2024-03-21
卷期号:143 (12): 1181-1192
被引量:1
标识
DOI:10.1182/blood.2023022865
摘要
Abstract Vitamin A plays a key role in the maintenance of gastrointestinal homeostasis and promotes a tolerogenic phenotype in tissue resident macrophages. We conducted a prospective randomized double-blinded placebo-controlled clinical trial in which 80 recipients of hematopoietic stem cell transplantation (HSCT) were randomized 1:1 to receive pretransplant high-dose vitamin A or placebo. A single oral dose of vitamin A of 4000 IU/kg, maximum 250 000 IU was given before conditioning. The primary end point was incidence of acute graft-versus-host disease (GVHD) at day +100. In an intent-to-treat analysis, incidence of acute GVHD was 12.5% in the vitamin A arm and 20% in the placebo arm (P = .5). Incidence of acute gastrointestinal (GI) GVHD was 2.5% in the vitamin A arm (P = .09) and 12.5% in the placebo arm at day +180. Incidence of chronic GVHD was 5% in the vitamin A arm and 15% in the placebo arm (P = .02) at 1 year. In an “as treated” analysis, cumulative incidence of acute GI GVHD at day +180 was 0% and 12.5% in recipients of vitamin A and placebo, respectively (P = .02), and cumulative incidence of chronic GVHD was 2.7% and 15% in recipients of vitamin A and placebo, respectively (P = .01). The only possibly attributable toxicity was asymptomatic grade 3 hyperbilirubinemia in 1 recipient of vitamin A at day +30, which self-resolved. Absolute CCR9+ CD8+ effector memory T cells, reflecting gut T-cell trafficking, were lower in the vitamin A arm at day +30 after HSCT (P = .01). Levels of serum amyloid A-1, a vitamin A transport protein with proinflammatory effects, were lower in the vitamin A arm. The vitamin A arm had lower interleukin-6 (IL-6), IL-8, and suppressor of tumorigenicity 2 levels and likely a more favorable gut microbiome and short chain fatty acids. Pre-HSCT oral vitamin A is inexpensive, has low toxicity, and reduces GVHD. This trial was registered at www.ClinicalTrials.gov as NCT03202849.
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