# Vitamin D and Hemopoietic Stem Cell Transplantation: Clinical Guidance for GVHD Management and Post-Transplant Outcomes

## TL;DR

This review discusses how vitamin D affects immune processes during stem cell transplants and offers guidance on managing vitamin D levels to improve outcomes.

## Contribution

The paper provides clinical strategies for preventing vitamin D deficiency during stem cell transplantation based on indirect evidence and biological mechanisms.

## Key findings

- Low vitamin D levels are common during stem cell transplants and linked to immune issues and infections.
- Maintaining vitamin D levels above 30 ng/mL by day +30 is suggested as a supportive strategy.
- Supplementation is generally safe but requires monitoring for hypercalcemia in at-risk patients.

## Abstract

Vitamin D regulates key immune processes involved in allogeneic hematopoietic stem cell transplantation. Many immune and barrier cells can locally activate vitamin D, allowing it to modulate inflammation and immune reactivity. During the transplant period, factors such as limited sunlight exposure, reduced intake, mucosal injury, cholestasis and corticosteroid use frequently lead to low vitamin D levels, exactly when antigen presentation and immune recovery are most active. This review summarizes how vitamin D status changes before and after transplantation and how deficiency relates to graft-versus-host disease, relapse, infections, engraftment, bone health and survival. It also discusses strategies to prevent severe deficiency, including pre-conditioning supplementation, reassessment around day 30, and dose adjustment if needed. When gastrointestinal absorption is impaired, intramuscular or oral thin-film formulations may be useful. Given the high prevalence of vitamin D deficiency after hematopoietic stem cell transplantation and the generally favorable safety profile of physiologic supplementation, maintaining serum 25-hydroxyvitamin D concentrations ≥30 ng/mL by approximately day +30 may represent a pragmatic supportive strategy. However, it is important to emphasize that, to date, randomized clinical trials demonstrating a direct effect of vitamin D repletion on transplant outcomes such as graft-versus-host disease incidence, immune reconstitution, or survival remain limited. From a clinical perspective, the rationale for monitoring and correcting vitamin D deficiency in hematopoietic stem cell transplantation recipients primarily derives from indirect evidence linking low 25-hydroxyvitamin D levels with impaired immune recovery, increased infection risk, and skeletal complications in observational studies. Potential benefits therefore include support for bone health and maintenance of physiologic immunomodulatory pathways. The principal risks of supplementation at conventional doses are limited and mainly relate to hypercalcemia in susceptible individuals, particularly those with renal impairment, granulomatous disease, or dysregulated calcium metabolism, underscoring the importance of biochemical monitoring.

Vitamin D is a pleiotropic secosteroid with endocrine and intracrine actions that influence key phases of allogeneic hematopoietic stem cell transplantation. Epithelial barriers, antigen-presenting cells and effector lymphocytes express the vitamin D receptor and enzymes required for local activation, allowing circulating 25-hydroxyvitamin D to be converted into its active form and modulate immune interactions. During the peri-transplant period, sunlight deprivation, reduced intake, mucosal injury, cholestasis and corticosteroid exposure markedly reduce vitamin D levels at a time when antigen presentation and immune reconstitution occur. This review integrates mechanistic immunology with clinical observations and interventional data to outline strategies that prevent severe deficiency. It summarizes epidemiology before and after transplantation, associations with acute and chronic graft-versus-host disease, relapse, engraftment, infections, bone health and survival, and evaluates dosing approaches including pre-conditioning loading and reassessment at day thirty with escalation if needed. Absorption-savvy formulations such as oral thin-film and intramuscular cholecalciferol are considered when gastrointestinal function is compromised. Given the high prevalence of deficiency, biological plausibility, safety and low cost, a structured approach that includes screening, repletion and monitoring to achieve concentrations of at least thirty nanograms per milliliter by day thirty represents a pragmatic and low-risk component of supportive care pending definitive evidence.