Faculty Collaboration Database

Transforming growth factor-β1 functional polymorphisms in myeloablative sibling hematopoietic stem cell transplantation. Bone Marrow Transplant 2017 May;52(5):739-744

Date

01/31/2017

Pubmed ID

28134923

DOI

10.1038/bmt.2016.355

Scopus ID

2-s2.0-85010931341 (requires institutional sign-in at Scopus site)   6 Citations

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.

Author List

Berro M, Palau Nagore MV, Rivas MM, Longo P, Foncuberta C, Vitriú A, Remaggi G, Martínez Rolon J, Jaimovich G, Requejo A, Feldman L, Padros K, Rodríguez MB, Shaw BE, Larripa I, Belli CB, Kusminsky GD

Author

Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Donor Selection
Female
Genotype
Graft vs Host Disease
Hematologic Neoplasms
Hematopoietic Stem Cell Transplantation
Humans
Male
Myeloablative Agonists
Polymorphism, Single Nucleotide
Recurrence
Siblings
Survival Analysis
Tissue Donors
Transforming Growth Factor beta1
Transplantation Conditioning
Treatment Outcome