RT Journal Article
T1 Vitamin D Modifies the Incidence of Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation Depending on the Vitamin D Receptor (VDR) Polymorphisms.
A1 Carrillo-Cruz, Estrella
A1 Garcia-Lozano, Jose R
A1 Marquez-Malaver, Francisco J
A1 Sanchez-Guijo, Fermin M
A1 Montero-Cuadrado, Isabel
A1 Ferra I Coll, Christelle
A1 Valcarcel, David
A1 Lopez-Godino, Oriana
A1 Cuesta, Marian
A1 Parody, Rocio
A1 Lopez-Corral, Lucia
A1 Alcoceba, Miguel
A1 Caballero-Velazquez, Teresa
A1 Rodriguez-Gil, Alfonso
A1 Bejarano-Garcia, Jose A
A1 Lopes-Ramos, Teresa
A1 Perez-Simon, Jose A
K1 Case-Control Studies
K1 Cholecalciferol
K1 Graft vs Host Disease
K1 Haplotypes
K1 Hematopoietic Stem Cell Transplantation
AB 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 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. 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, Pinteraction  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.
PB American Association for Cancer Research
YR 2019
FD 2019
LK http://hdl.handle.net/10668/13898
UL http://hdl.handle.net/10668/13898
LA en
NO Carrillo-Cruz E, García-Lozano JR, Márquez-Malaver FJ, Sánchez-Guijo FM, Montero Cuadrado I, Ferra I, et al. Vitamin D Modifies the Incidence of Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation Depending on the Vitamin D Receptor (VDR) Polymorphisms. Clin Cancer Res. 2019 Aug 1;25(15):4616-4623
NO This work was supported by grants to the CIBERONC(CB16/12/00480), the Instituto de Salud Carlos III (PI17/02177), Ministerio de sanidad y política social (EC10-304), Red TerCel, and ISCIII (RD16/0011/0015, RD16/0011/ 0035).
DS RISalud
RD Apr 18, 2025