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Clin Cancer Res. 2019 Aug 1;25(15):4616-4623. doi: 10.1158/1078-0432.CCR-18-3875. Epub 2019 May 1.

Vitamin D Modifies the Incidence of Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation Depending on the Vitamin D Receptor (VDR) Polymorphisms.

Author information

1
Department of Hematology, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla (IBIS)/CSIC/CIBERONC, Universidad de Sevilla, Seville, Spain.
2
Department of Immunology, Hospital Universitario Virgen del Rocío, Seville, Spain.
3
IBSAL-Hospital Universitario de Salamanca/CIBERONC, CIC-Universidad de Salamanca, Salamanca, Spain.
4
Institut Catalad'Oncologia, Hospital Germans Trias i Pujol, Barcelona, Spain.
5
Hospital Vall d'Hebron, Barcelona, Spain.
6
Hospital Carlos Haya, Málaga, Spain.
7
Institut Catala d'Oncologia, Hospital Duran i Reynals, Barcelona, Spain.
8
Instituto de Biomedicina de Sevilla (IBIS)/ CSIC/ CIBERONC, Universidad de Sevilla, Seville, Spain.
9
Department of Hematology, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla (IBIS)/CSIC/CIBERONC, Universidad de Sevilla, Seville, Spain. josea.perez.simon.sspa@juntadeandalucia.es.

Abstract

PURPOSE:

The biologically active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (vit D), has immunoregulatory properties via binding vitamin D receptor (VDR). In a prospective trial, we previously reported a reduction in the incidence of chronic GvHD (cGvHD) among patients who received vit D after allogeneic stem cell transplantation (allo-HSCT; Clinical Trials.gov: NCT02600988). Here we analyze the role of patients and donors' VDR SNPs on the immunomodulatory effect of vit D.

PATIENTS AND METHODS:

Patients undergoing allo-HSCT were included in a prospective phase I/II clinical trial (Alovita) in three consecutive cohorts: control (without vit D), low-dose (1,000 IU/day), and high-dose (5,000 IU/day) groups. Vit D was given from day -5 until +100 after transplant. Genotyping of four SNPs of the VDR gene, FokI, BsmI, ApaI, and TaqI, were performed using TaqMan SNP genotyping assays.

RESULTS:

We observed a decrease in the incidence of overall cGvHD at 1 year after allo-HSCT depending on the use or not of vit D among patients with FokI CT genotype (22.5% vs 80%, P = 0.0004) and among those patients without BsmI/ApaI/TaqI ATC haplotype (22.2% vs 68.8%, P = 0.0005). In a multivariate analysis, FokI CT genotype significantly influenced the risk of cGvHD in patients treated with vit D as compared with the control group (HR 0.143, P interaction < 0.001).

CONCLUSIONS:

Our results show that the immunomodulatory effect of vit D depends on the VDR SNPs, and patients carrying the FokI CT genotype display the highest benefit from receiving vit D after allo-HSCT.

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