title: Immunomodulatory Effect of Vitamin D after Allogeneic Stem Cell Transplantation: Results of a Prospective Multicenter Clinical Trial.
abstract: OBJECTIVE
  We describe the results of a prospective multicenter phase I/II trial evaluating the impact of the use of vitamin D (VitD) from day -5 to +100 on the outcome of patients undergoing allogeneic transplantation (EudraCT: 2010-023279-25; ClinicalTrials.gov: NCT02600988).
  
  
  METHODS
  A total of 150 patients were included in three consecutive cohorts of 50 patients each group: control group (CG, not receive VitD); low-dose group (LdD, received 1,000 IU VitD daily); and high-dose group (HdD, 5,000 IU VitD daily). We measured levels of VitD, cytokines, and immune subpopulations after transplantation.
  
  
  RESULTS
  No significant differences were observed in terms of cumulative incidence of overall and grades 2-4 acute GVHD in terms of relapse, nonrelapse mortality, and overall survival. However, a significantly lower cumulative incidence of both overall and moderate plus severe chronic GVHD (cGVHD) at 1 year was observed in LdD (37.5% and 19.5%, respectively) and HdD (42.4% and 27%, respectively) as compared with CG (67.5% and 44.7%, respectively; P < 0.05). In multivariable analysis, treatment with VitD significantly decreased the risk of both overall (for LdD: HR = 0.31, P = 0.002; for HdD: HR = 0.36, P = 0.006) and moderate plus severe cGVHD (for LdD: HR = 0.22, P = 0.001; for HdD: HR = 0.33, P = 0.01). VitD modified the immune response, decreasing the number of B cells and naïve CD8 T cells, with a lower expression of CD40L.
  
  
  CONCLUSIONS
  This is the first prospective trial that analyzes the effect of VitD postransplant. We observed a significantly lower incidence of cGVHD among patients receiving VitD. Interestingly, VitD modified the immune response after allo-SCT. Clin Cancer Res; 22(23); 5673-81. ©2016 AACR.
authors.affiliation: Servicio de Hematología, Hospital Universitario Virgen del Rocio/ Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Caballero-Velázquez
authors.affiliation: Servicio de Hematología, Hospital Universitario Virgen del Rocio/ Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Montero
authors.affiliation: Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Fermín
authors.initials: F
authors.lastname: Sánchez-Guijo
authors.affiliation: Servicio de Hematología, Hospital Universitario Virgen del Rocio/ Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Parody
authors.affiliation: Servicio de hematología, Hospital de Especialidades de Jerez, Zacatecas, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Saldaña
authors.affiliation: Servicio de Hematología, Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Valcarcel
authors.affiliation: Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Oriana
authors.initials: O
authors.lastname: López-Godino
authors.affiliation: Servicio de Hematología, Institut Catalad'Oncologia, Hospital Germans Trias i Pujol, Barcelona, Spain.
authors.forename: Christelle
authors.initials: C
authors.lastname: Ferra I Coll
authors.affiliation: Hospital Universitario Carlos Haya, Malaga, Spain.
authors.forename: Marian
authors.initials: M
authors.lastname: Cuesta
authors.affiliation: Department of Medical Biochemistry and Molecular Biology and Immunology, University of Seville School of Medicine, Seville, Spain.|Institute of Biomedicine of Seville, IBiS, Virgen del Rocío, University Hospital/CSIC/University of Seville, Seville, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Carrillo-Vico
authors.affiliation: Servicio de Hematología, Hospital Universitario Virgen del Rocio/ Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Luis I
authors.initials: LI
authors.lastname: Sánchez-Abarca
authors.affiliation: Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: López-Corral
authors.affiliation: Servicio de Hematología, Hospital Universitario Virgen del Rocio/ Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Márquez-Malaver
authors.affiliation: Servicio de Hematología, Hospital Universitario Virgen del Rocio/ Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, Sevilla, Spain. josea.perez.simon.sspa@juntadeandalucia.es.
authors.forename: José A
authors.initials: JA
authors.lastname: Pérez-Simón
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014184:Transplantation, Homologous / Q000379:methods; D014807:Vitamin D / Q000276:immunology*; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D014807:Vitamin D