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

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.