Vitamin A pre-allo-HSCT for the prevention of GvHD: results from a randomized phase II trial

Following allogeneic hematopoietic stem cell transplantation (allo-HSCT), some patients may develop acute gastrointestinal (GI) graft-versus-host disease (GvHD); a significant cause of non-relapse mortality.¹ A prominent precursor of GI GvHD is the disruption of GI homeostasis which can be affected by vitamin A levels.¹ Vitamin A has been shown to induce a tolerogenic phenotype in gut resident dendritic cells, with these cells then producing lower levels of certain proinflammatory cytokines. In addition, low plasma vitamin A levels have been shown to be associated with a higher incidence of acute GvHD (aGvHD).¹

Below, we summarize key data from a randomized phase II trial of oral vitamin A for GvHD in children and young adults (NCT03202849), published by Khandelwal et al.¹ in Blood.

Study design¹

• Patients were eligible if their pre-allo-HSCT serum vitamin A levels were <75th centile of the normal range for age.
• In total, 80 patients aged ≥1 year old were enrolled, with 40 patients receiving a single oral dose of vitamin A (4,000 IU/kg) pre-allo-HSCT and 40 patients receiving a placebo.
• Two analyses were performed: anintent-to-treat analysis and an as-treated analysis.
• The primary endpoint was the incidence of acute GvHD (aGvHD) by Day 100 posttransplant.

Key findings¹

During the intent-to-treat analysis, the incidence of Grade 1–4 aGvHD by Day 100 was 12.5% in the vitamin A cohort and 20% in the placebo cohort (p = 0.5). Figure 1 illustrates secondary endpoint findings for the cumulative incidence of GvHD.

In the as-treated analysis, the incidence of Grade 1–4 aGvHD by Day 100 was 8% in the vitamin A cohort and 20% in the placebo cohort (p = 0.2). Below, Table 1 summarizes the cumulative incidence of GvHD in the as-treated analyses.

Table 1. Occurrence of GvHD in patients who received vitamin A pre-allo-HSCT vs placebo, in the ‘as treated’ analyses*