Graft-versus-host disease (GVHD) following allogeneic HSCT and donor lymphocyte infusion is a significant cause of morbidity and mortality for patients undergoing transplantation, and the immune-regulatory properties of vitamin D may affect the likelihood of developing this complication. One study showed that patients with lower 25(OH)D3 levels at the time of transplantation were 3 times likelier to develop chronic GVHD while a second paper found there was a higher 2 year cumulative incidence of chronic GVHD (63.8% vs 23.8%) and extensive chronic GVHD (54.5% versus 14.3%) in patients with lower 25(OH)D3 levels before HSCT compared with patients with high levels. In contrast, a third study could not reproduce these results.

“There remains a paucity of clinical studies focusing on the role of vitamin D deficiency in the GVHD context,” wrote Dr Ros-Soto and colleagues. “Nearly half of [the studies] failed to find an association between this vitamin and acute or chronic GVHD; thus no definitive conclusions can be drawn from them.”

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Despite the conflicting evidence, some physicians are incorporating vitamin D into the treatment regimen of patients undergoing HSCT.

“We currently add vitamin D post-transplant to all of our patients undergoing transplantation based on our phase 1/2 trial ( Identifier: NCT02600988),” said José A Pérez-Simón, MD, of the Hospital Universitario Virgen del Rocío-Virgen Macarena in Spain.

“Of course, this cannot be considered a standard approach for allotransplant in general, [because] a prospective phase 3 trial is lacking,” he emphasized. “But as far as we know, there is no toxicity, and the potential benefit is important. In addition, it is a low cost procedure.”

But it is also unlikely that there will ever be a phase 3 trial, as it would be extremely difficult to get financial support to conduct a large trial with such an inexpensive drug, Dr Perez-Simon pointed out. “So I’m not sure we will be able to get enough evidence to consider using vitamin D as a standard therapy.”

He added that “as long as we do not have this evidence, and considering the information available, I prefer to give vitamin D to all of my patients, but I understand this recommendation is not based on solid prospective comparative data.”

Similarly, the study authors agreed that given its potential benefits, low cost, and favorable side effect profile, “consideration of vitamin D levels and its supplementation could be easily incorporated into prospective studies in GVHD, including clinical trials of novel therapeutics, supportive care, and biomarkers.”


1. Ros-Soto J, Anthias C, Madrigal A, Snowden JA. “Vitamin D: Is it important in haematopoietic stem cell transplantation? A review [published online November 6, 2018]. Bone Marrow Transplant. doi: 10.1038/s41409-018-0377-0