RESUMO
We investigated the impact of the number of infused and reconstituted immunocompetent cells including dendritic cells (DCs) on clinical outcome of patients with hematologic malignancies undergoing an allogeneic peripheral blood stem cell transplantation. Sixty-nine consecutive patients with hematologic malignancies were included in the analysis. The median age of the cohort was 32 years (range: 2-62 years) and there were 39 (57%) males. Twenty-one (30%) patients relapsed with a cumulative incidence of 44 % +/- 14% at a median follow up of 28 months. On a multivariate analysis, a high plasmacytoid dendritic cell (PC) content in the graft was associated with higher risk of relapse. The patients were further categorized based on the median PC counts in the graft as high (> or =2.3 x 10(6)/kg) and low (<2.3 x 10(6)/kg) groups. The baseline characteristics of these 2 groups were comparable. The group that had a high PC content in the graft had significantly higher risk of relapse and lower overall survival (OS) and event-free survival (EFS). Our data suggests that PC content in the graft predicts clinical outcomes such as relapse and survival in patients with hematologic malignancies undergoing an allogeneic HLA matched related peripheral blood stem cell transplantation. There is potential for pretransplant manipulation of this cellular subset in the graft.
Assuntos
Células Dendríticas/transplante , Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplantes/efeitos adversos , Adolescente , Adulto , Fatores Etários , Contagem de Células Sanguíneas , Contagem de Células , Criança , Pré-Escolar , Células Dendríticas/citologia , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Contagem de Plaquetas , Recidiva , Fatores de Risco , Análise de Sobrevida , Linfócitos T Auxiliares-Indutores/citologia , Quimeras de Transplante/sangue , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
We have prospectively analyzed cellular immune reconstitution (IR) in 63 consecutive pediatric patients with beta thalassemia major who underwent an HLA matched related allogeneic bone marrow transplant (BMT). Samples from bone marrow graft and posttransplant peripheral blood samples from recipients at specified time points were assessed for IR of cellular subsets. The median age of the cohort was 7 years, and there were 37 (59%) males. A CD34 cell dose above the median value of 7.3 x 10(6)/kg had a lower incidence of bacterial (P = .003) and fungal (P = .003) infections in the posttransplant period, and was not associated with an increased risk of graft-versus-host disease (GVHD). Among cases that did develop grade II-IV GVHD the absolute CD8 (116 versus 52 cells/microL, P = .012), CD8 naïve (74 versus 9 cells/microL, P = .005), and CD8 memory counts (44 versus 21 cells/microL, P = .010) were significantly higher on day 15. Fifteen patients (24%) rejected their graft (7 primary and 8 secondary). The day 28 natural killer (NK) cell count was significantly associated with secondary graft rejection, event-free survival (EFS), and overall survival (OS) (P = .044, .013, and .034, respectively). On a multivariate analysis, patients with a day 28 NK cell count below the median value of 142/microL had a significantly higher rejection rate (hazard ratio [HR] = 11.1, P = .038) and a lower EFS (HR = 16.3, P = .034).
Assuntos
Transplante de Medula Óssea/métodos , Sistema Imunitário/fisiologia , Agonistas Mieloablativos/uso terapêutico , Regeneração , Talassemia beta/terapia , Adolescente , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/imunologia , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Histocompatibilidade , Humanos , Sistema Imunitário/citologia , Cinética , Contagem de Linfócitos , Masculino , Infecções Oportunistas , Análise de Sobrevida , Doadores de Tecidos , Transplante Homólogo , Resultado do TratamentoRESUMO
Dendritic cells (DC) are antigen-presenting cells involved in induction and regulation of immune responses. We investigated the impact of the number of infused and day 28 dendritic cells on the development of acute and chronic GVHD (aGVHD, cGVHD). Monocytoid (MC) and plasmacytoid (PC) dendritic cells were characterized as lin(-)HLA-DR(+)CD11c(+) and lin(-)HLA-DR(+)CD123(+), respectively. Sixty-eight consecutive patients who underwent HLA matched related granuloyte-colony stimulating factor (G-CSF) mobilized allogeneic PBSCT, from February 2005 to May 2006, were included in the analysis. Twenty-three patients developed aGVHD (grade II-IV) and 21 patients had cGVHD. On a univariate analysis the day 28 total DC and the day 28 MC and PC dendritic cells as continuous variables were significantly associated with development of aGVHD and cGVHD. Using an ROC plot analysis a cutoff value for total DC = 10.7/microL, MC = 9.7/microL, and PC = 4.5/microL on day 28 gave the highest likelihood ratios for aGVHD (2.7, 2.14, and 3.29, respectively). On a multivariate analysis, a low day 28 PC (Assuntos
Antígeno CD11c/sangue
, Células Dendríticas
, Doença Enxerto-Hospedeiro/sangue
, Antígenos HLA-DR/sangue
, Subunidade alfa de Receptor de Interleucina-3/sangue
, Contagem de Leucócitos
, Transplante de Células-Tronco de Sangue Periférico
, Plasmócitos
, Receptores de Interleucina-3/sangue
, Doença Aguda
, Adolescente
, Adulto
, Criança
, Pré-Escolar
, Doença Crônica
, Células Dendríticas/patologia
, Feminino
, Doença Enxerto-Hospedeiro/etiologia
, Doença Enxerto-Hospedeiro/mortalidade
, Doença Enxerto-Hospedeiro/patologia
, Fator Estimulador de Colônias de Granulócitos/administração & dosagem
, Doenças Hematológicas/sangue
, Doenças Hematológicas/complicações
, Doenças Hematológicas/mortalidade
, Doenças Hematológicas/terapia
, Mobilização de Células-Tronco Hematopoéticas
, Teste de Histocompatibilidade
, Humanos
, Incidência
, Masculino
, Pessoa de Meia-Idade
, Transplante de Células-Tronco de Sangue Periférico/mortalidade
, Plasmócitos/patologia
, Valor Preditivo dos Testes
, Fatores de Risco
, Fatores de Tempo
, Transplante Homólogo