title: Transforming growth factor-β1 functional polymorphisms in myeloablative sibling hematopoietic stem cell transplantation.
abstract: Hematopoietic stem cell transplantation (HSCT) with sibling donors (s.d.) is a life-saving intervention for patients with hematological malignancies. Numerous genetic factors have a role in transplant outcome. Several functional polymorphisms have been identified in TGF-β1 gene, such as single-nucleotide polymorphism (SNP) at +29C>T within exon 1. Two hundred and forty five patient/donor pairs who underwent a s.d. HSCT in our centers were genotyped for this SNP. In the myeloablative cohort, +29CC donors were associated with an increase in severe chronic GvHD (32% vs 16%, hazard ratio (HR) 9.0, P=0.02). Regarding survival outcomes, +29CC patients developed higher non relapse mortality (NRM) (1-5 years CC 28-32% vs TC/TT 7-10%; HR 5.1, P=0.01). Recipients of +29TT donors experienced a higher relapse rate (1-5 years TT 37-51% vs TC 19-25% vs CC 13%-19%; HR 2.4, P=0.01) with a decreased overall survival (OS) (1-5 years TT 69-50% vs TC/CC 77-69%; HR 1.9, P=0.05). Similar to previous myeloablative unrelated donors HSCT results, we confirmed that +29CC patients had higher NRM. In addition we found that +29TT donors might be associated with a higher relapse rate and lower OS. These results should be confirmed in larger series. Identification of these SNPs will allow personalizing transplant conditioning and immunosuppressant regimens, as well as assisting in the choice of the most appropriate donor.
authors.affiliation: Unidad de Trasplante Hematopoyético, Hospital Universitario Austral, Buenos Aires, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Berro
authors.affiliation: Laboratorio de Genética Hematológica; Instituto de Medicina Experimental (IMEX-CONICET)/Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: M V
authors.initials: MV
authors.lastname: Palau Nagore
authors.affiliation: Unidad de Trasplante Hematopoyético, Hospital Universitario Austral, Buenos Aires, Argentina.
authors.forename: M M
authors.initials: MM
authors.lastname: Rivas
authors.affiliation: Unidad de Trasplante Hematopoyético, Hospital Universitario Austral, Buenos Aires, Argentina.
authors.forename: P
authors.initials: P
authors.lastname: Longo
authors.affiliation: Unidad de Transplante Hematopoyetico, Instituto Alexander Fleming, Buenos Aires, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Foncuberta
authors.affiliation: Unidad de Transplante Hematopoyetico, Instituto Alexander Fleming, Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Vitriú
authors.affiliation: Unidad de Transplante Hematopoyetico, FUNDALEU, Buenos Aires, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Remaggi
authors.affiliation: Unidad de Transplante Hematopoyetico, FUNDALEU, Buenos Aires, Argentina.
authors.forename: J
authors.initials: J
authors.lastname: Martínez Rolon
authors.affiliation: Unidad de Transplante Hematopoyetico, Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Jaimovich
authors.affiliation: Unidad de Transplante Hematopoyetico, Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Requejo
authors.affiliation: Unidad de Transplante Hematopoyetico, Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Feldman
authors.affiliation: Primer Centro Argentino de Inmunogenética (PRICAI), Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: K
authors.initials: K
authors.lastname: Padros
authors.affiliation: Primer Centro Argentino de Inmunogenética (PRICAI), Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: M B
authors.initials: MB
authors.lastname: Rodríguez
authors.affiliation: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Shaw
authors.affiliation: Laboratorio de Genética Hematológica; Instituto de Medicina Experimental (IMEX-CONICET)/Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: I
authors.initials: I
authors.lastname: Larripa
authors.affiliation: Laboratorio de Genética Hematológica; Instituto de Medicina Experimental (IMEX-CONICET)/Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: C B
authors.initials: CB
authors.lastname: Belli
authors.affiliation: Unidad de Trasplante Hematopoyético, Hospital Universitario Austral, Buenos Aires, Argentina.
authors.forename: G D
authors.initials: GD
authors.lastname: Kusminsky
mesh_terms: D000328:Adult; D046148:Donor Selection / Q000379:methods; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality / Q000592:standards; D006801:Humans; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D035781:Siblings; D016019:Survival Analysis; D014019:Tissue Donors; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome
chemical_list: D019653:Myeloablative Agonists; D053773:Transforming Growth Factor beta1