title: UGT2B17 minor histocompatibility mismatch and clinical outcome after HLA-identical sibling donor stem cell transplantation.
abstract: Minor histocompatibility Ags (mHags) have been implicated in the pathogenesis of GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Uridine diphospho-glucuronosyltransferase 2B17 (UGT2B17) gene deletion may act as a mHag and its association with acute GVHD (aGVHD) has been described. We retrospectively studied the clinical impact of a UGT2B17 mismatch in a cohort of 1127 patients receiving a HSCT from an HLA-identical sibling donor. UGT2B17 mismatch was present in 69 cases (6.1%). Incidence of severe aGVHD was higher in the UGT2B17 mismatched pairs (22.7% vs 14.6%), but this difference was not statistically significant (P: 0.098). We did not detect differences in chronic GVHD, overall survival, relapse-free survival, transplant-related mortality or relapse. Nevertheless, when we analyzed only those patients receiving grafts from a male donor (616 cases), aGVHD was significantly higher in the UGT2B17 mismatched group (25.1% vs 12.8%; P: 0.005) and this association was confirmed by the multivariate analysis (P: 0.043; hazard ratio: 2.16, 95% confidence interval: 1.03-4.57). Overall survival was worse for patients mismatched for UGT2B17 (P: 0.005). We conclude that UGT2B17 mismatch has a negative clinical impact in allogeneic HSCT from HLA-identical sibling donors only when a male donor is used. These results should be confirmed by other studies.
authors.affiliation: Clinical Hematology Department, Institut Català d'Oncologia, IDIBGi, Girona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Santos
authors.affiliation: Clinical Hematology Department, Institut Català d'Oncologia, IDIBGi, Girona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Rodríguez-Romanos
authors.affiliation: Hematology Department, Hospital Morales Meseguer, Murcia, Spain.
authors.forename: J B
authors.initials: JB
authors.lastname: Nieto
authors.affiliation: Hematology Department, Hospital Gregorio Marañón, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Buño
authors.affiliation: Hematology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Vallejo
authors.affiliation: Hematology Department, Hospital Carlos Haya, Málaga, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Jiménez-Velasco
authors.affiliation: Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Brunet
authors.affiliation: Hematology Department, Hospital Gregorio Marañón, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Buces
authors.affiliation: Hematology Department, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: López-Jiménez
authors.affiliation: Hematology Department, Hospital Universitario, Salamanca, Spain.
authors.forename: M
authors.initials: M
authors.lastname: González
authors.affiliation: Institut Català d'Oncologia, Badalona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Ferrá
authors.affiliation: Hematology Department, Hospital Son Espases, Palma de Mallorca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Sampol
authors.affiliation: Hematology Department, Hospital La Princesa, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: de la Cámara
authors.affiliation: Hematology Department, Hospital Clínic, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Martínez
authors.affiliation: Clinical Hematology Department, Institut Català d'Oncologia, IDIBGi, Girona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Gallardo
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics*; D006086:Graft vs Host Disease / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000517:prevention & control; D006680:HLA Antigens; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D035781:Siblings; D015996:Survival Rate; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase