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 hematologicalmalignancies. Numerous genetic factors have a role in transplant outcome. Several functional polymorphisms have been identifiedin TGF-β1 gene, such as single-nucleotide polymorphism (SNP) at +29C4T within exon 1. Two hundred and forty five patient/donorpairs who underwent a s.d. HSCT in our centers were genotyped for this SNP. In the myeloablative cohort, +29CC donors wereassociated 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). Recipientsof +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) witha decreased overall survival (OS) (1?5 years TT 69?50% vs TC/CC 77?69%; HR 1.9, P = 0.05). Similar to previous myeloablativeunrelated donors HSCT results, we confirmed that +29CC patients had higher NRM. In addition we found that +29TT donors mightbe associated with a higher relapse rate and lower OS. These results should be confirmed in larger series. Identification of theseSNPs will allow personalizing transplant conditioning and immunosuppressant regimens, as well as assisting in the choice of themost appropriate donor.