RESUMO
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-ß1 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.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doadores de Tecidos , Fator de Crescimento Transformador beta1/genética , Adulto , Seleção do Doador/métodos , Feminino , Genótipo , Doença Enxerto-Hospedeiro/genética , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Masculino , Agonistas Mieloablativos/uso terapêutico , Polimorfismo de Nucleotídeo Único , Recidiva , Irmãos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Resultado do TratamentoRESUMO
BACKGROUND AND METHODS: We analyze myelodysplastic patients with the 5q- marker as sole abnormality, or with additional anomalies, and their relationship to clinical evolution. The study was performed on 12 patients (6 females and 6 males): 3 with refractory anemia (RA), 5 with RA with ring sideroblasts (RA-S), 3 RA with excess of blasts (RAEB) and 1 with RAEB in transformation (RAEB-T). The cytogenetic study was carried out on bone marrow cells at the time of diagnosis. The G- banding technique was used for chromosome identification. The follow-up was for 50 months. RESULTS AND CONCLUSIONS: Five patients (3 with RA and 2 with RA-S) showed a single 5q- marker. They had a long survival without evolution to leukemia. All cases with 5q- plus additional abnormalities: del(12p), del(7q), del(14q), i(11q) and i(17q), showed a neoplastic evolution in a short period of time. We can conclude that the presence of the 5q- marker with complex karyotypes or additional abnormalities is associated with a high risk of neoplastic evolution, indicating the prognostic value of cytogenetic study in myelodysplasia.
