RESUMO
Chronic graft-versus-host disease is the major long-term complication after allogeneic stem cell transplantation with a suboptimal response rate to current treatments. Therefore, clinical efficacy and changes in lymphocyte subsets before and after rituximab treatment were evaluated in a prospective phase II study in patients with steroid-refractory chronic graft-versus-host disease. Overall response rate was 61%. Only responding patients were found to have increased B-cell numbers prior to treatment. B cells had a naïve-antigen-presenting phenotype and were mainly CD5 negative or had a low CD5 expression. Normal B-cell homeostasis was reestablished in responding patients one year after ritxumab treatment and associated with a significant decline in skin-infiltrating CD8(+) T cells, suggesting that host B cells play a role in maintaining pathological CD8(+) T-cell responses. Imbalances in B-cell homeostasis could be used to identify patients a priori with a higher chance of response to rituximab treatment (Eudra-CT 2008-004125-42).
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/imunologia , Imunofenotipagem , Imunossupressores/uso terapêutico , Anticorpos Monoclonais Murinos/administração & dosagem , Linfócitos B/imunologia , Doença Crônica , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Depleção Linfocítica , Fenótipo , Prognóstico , Rituximab , Transplante Homólogo , Resultado do TratamentoRESUMO
We investigated the role of donor cytomegalovirus (CMV) serostatus on reactivation of CMV infection in CMV-infected transplant recipients. Reactivation of CMV infection occurred more frequently in patients receiving a CMV-positive graft but was less severe than in patients receiving a CMV-negative graft. These data suggest roles for both virus as well as CMV-specific immunity present in the graft.
Assuntos
Infecções por Citomegalovirus/patologia , Citomegalovirus/isolamento & purificação , Índice de Gravidade de Doença , Transplante de Células-Tronco , Doadores de Tecidos , Ativação Viral , Citomegalovirus/imunologia , Infecções por Citomegalovirus/imunologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
Chronic graft-versus-host-disease (cGVHD) is the major cause of late morbidity and mortality after allogeneic stem cell transplantation. B cells have been reported to be involved in mediating cGVHD. To assess whether preemptive host B cell depletion prevents extensive cGVHD after allogeneic reduced-intensity conditioning transplantation (RICT), 173 patients treated with RICT for various hematologic diseases, who had or had not received Rituximab (Rtx) within 6 month prior to RICT, were analyzed retrospectively. Rtx treatment within 6 months prior to RICT reduced extensive cGVHD significantly from 45.8% to 20.1%. We hypothesize that most likely host B cells initiate cGVHD, and thus, host B cell depletion prior to RICT by Rtx might be a valuable strategy to reduce extensive cGVHD after RICT.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Linfócitos B/efeitos dos fármacos , Doença Enxerto-Hospedeiro/prevenção & controle , Doenças Hematológicas/cirurgia , Depleção Linfocítica/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Alemtuzumab , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais Murinos , Anticorpos Antineoplásicos/uso terapêutico , Soro Antilinfocitário/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/imunologia , Doença Crônica , Terapia Combinada , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Doenças Hematológicas/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Pré-Medicação , Estudos Retrospectivos , Rituximab , Tamanho da Amostra , Adulto JovemRESUMO
After infection with the Epstein - Barr virus, a common gammaherpes virus which infects and persists in the B cells, an equilibrium is established in which newly infected and differentiating B cells are controlled by cytotoxic T cell (CTL) responses. Disturbance of this equilibrium, which can occur in immunocompromised situations, can lead to uncontrolled lymphoproliferation and subsequent development of non-Hodgkin Lymphomas (NHL). Here, we review the role of immunesurveillance of EBV-infected B cells and two situations where immunesurveillance is altered because of immunodeficiencies, transplantation recipients and HIV infection, which can lead to EBV-mediated NHL. In transplant recipients, immunosuppression prior and during transplantation can lead to lack of immunesurveillance and results in proliferation of infected B cells, which would normally be controlled by CTL responses. Interestingly, in HIV infection both deregulation of the normal B cell biology and a reduction in immunity play a role in developing NHL. Therefore, the nature of EBV infection in HIV-positive subjects is very different from that in transplanted individuals, in whom (re-)appearance of EBV-specific CD8(+) T cells - either by a decrease in immune suppression or infusion of donor lymphocytes - immediately leads to a decrease in EBV load.
