Assuntos
Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Antígenos de Histocompatibilidade Classe I/genética , Doadores Vivos , Polimorfismo Genético , Doença Aguda , Doença Crônica , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Seleção de Pacientes , Análise de Regressão , Doadores de Tecidos , Falha de Tratamento , Resultado do Tratamento , Antígenos HLA-ERESUMO
We investigated the impact of ABO and Rhesus (Rh) blood group matching on the outcome of hematopoietic stem cell transplantation (HSCT) of 154 patients matched at 10/10 HLA loci with unrelated donors. ABO and Rh, as potential risk factors, were modeled with the clinical outcome--acute and chronic graft-versus-host disease (aGVHD, cGVHD), relapse, treatment-related mortality (TRM), and overall survival (OS)--by simple, multiple, and competing risk analyses. We found that minor ABO-mismatches represent a significant risk factor for aGVHD (II-IV) with an estimated risk increase of almost 3-fold (hazard ratio [HR]=2.92, 95% confidence interval [CI]: 1.43-5.95, P=.003), and even 4-fold for aGVHD (III-IV) (HR=4.24, 95% CI: 1.70-10.56, P=.002), but not for other transplant endpoints. No significant association of the Rh matching status with any of the HSCT endpoints was seen. These results suggest that ABO minor mismatches may play a role in aGvHD pathophysiology, possibly by providing the setting for T cell activation and antibody mediated damage. To decrease the risk of aGVHD, ABO matching should be considered in HSCT.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/complicações , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Adolescente , Adulto , Doenças da Medula Óssea/cirurgia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Antígenos HLA/imunologia , Humanos , Leucemia/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
The interpretation of the role of HLA-DPB1 in unrelated haematopoietic stem cell transplantation (HSCT) is subject to discussion. We have investigated the role of HLA-DPB1 allele matching in HSCT outcomes in 161 recipients who were HLA-A, -B, -C, -DRB1 and -DQB1-matched with their unrelated donors at the allelic level (10/10). In addition, we analysed the association of polymorphic amino acid mismatches of DPB1 molecule with HSCT end-points, and a previously published permissiveness concept. HLA-DPB1 allele mismatches were significantly associated with an increased incidence of acute graft-versus-host disease (aGvHD) and worse overall survival (OS). The mismatch at amino acid position 69 significantly increased the risk for transplant-related mortality (TRM). Risk factors for aGvHD also included mismatches at positions 8, 9, 35, 76 and 84. This is to our knowledge, the first report of an in vivo effect of single amino acid mismatches on HSCT outcomes. In this study, grouping of allelic mismatches into permissive and non-permissive categories and their association with transplantation end-points was relevant for TRM but not for other clinical end-points.