An increased risk of acute graft vs host disease (GVHD) was recently demonstrated in patients with thalassemia major (TM) who had low vitamin D3 levels prior to undergoing hematopoietic stem cell transplantation (HSCT). This is based on the results of a study reported in Clinical Transplantation.

Vitamin D deficiency (VDD) has appeared to be associated with immunomodulatory characteristics in autoimmune conditions but has shown unclear relationships with GVHD-related outcomes with HSCT. In this retrospective study, the researchers aimed to determine if VDD showed associations with HSCT outcomes for patients with TM.

The study featured a relatively homogeneous population of patients below 20 years of age being treated for TM with HSCT at a hospital in Antalya, Turkey. Patients were identified as having VDD if they had a 25-OH vitamin D3 level below 20 ng/mL before HSCT and the conditioning regimen. After HSCT, all patients received vitamin D3 supplementation at 400 to 800 IU per day for 6 months, regardless of pre-HSCT vitamin D3 status. The study’s primary objective was to compare early outcomes following HSCT based on a pre-HSCT vitamin D3 level of either <20 ng/mL or ≥20 ng/mL.

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There were 100 patients included in analyses. In this population, 52 patients had pre-HSCT vitamin D3 levels below 20 ng/mL, and 48 patients had pre-HSCT vitamin D3 levels at or above 20 ng/mL. With vitamin D3 supplementation after HSCT, patients with pre-HSCT VDD showed significantly higher vitamin D3 levels by 3 months after HSCT (P <.01).

Pre-HSCT vitamin D3 levels appeared to show no associations with outcomes such as survival, success of HSCT, engraftment days, chimerism levels, total days of hospitalization, or infections with sepsis. Overall, most HSCT-related complications did not appear to differ during the initial 6 months after HSCT between groups. The exception to this was acute GVHD of grades 2 to 4, which appeared to be more common after HSCT among patients with VDD before HSCT, occurring in 17 of these patients, compared with 5 patients in the group with higher pre-HSCT vitamin D3 levels (P <.01).

Multivariate analysis of pre-HSCT characteristics suggested that the pre-HSCT vitamin D3 category was a significant prognostic factor for acute GVHD of grades 2 to 4. Patients with VDD before HSCT had a significantly greater risk of this outcome than patients without VDD did (hazard ratio [HR], 7.3; 95% CI, 2.0-26.8; P <.01). Use of peripheral blood as the stem cell source was also associated with greater risk of this outcome (HR, 8.5; 95% CI, 1.9-37.3; P <.01).

In this study, the researchers concluded that with TM, pre-HSCT VDD was a significant risk factor for acute GVHD, especially in the context of peripheral blood being used as the stem cell source. “All patients with TM should be screened in terms of VDD before HSCT and every effort should be made in supplementation of vitamin D,” the researchers wrote in their report.


Daloğlu H, Uygun V, Öztürkmen S, Yalçın K, Karasu G, Yeşilipek A. Pre-transplantation vitamin D deficiency increases acute graft-versus-host disease after hematopoietic stem cell transplantation in thalassemia major patients. Clin Transplant. Published online December 2, 2022. doi:10.1111/ctr.14874