RESUMO
BACKGROUND: Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear. METHODS: We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX 'group 3'. RESULTS: Overall, 217 patients were identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of 3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5-33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively (P=0.009). CONCLUSIONS: The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/prevenção & controle , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Metotrexato/administração & dosagem , Injúria Renal Aguda/induzido quimicamente , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/secundário , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Injeções Espinhais , Linfoma Difuso de Grandes Células B/patologia , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Recidiva , Estudos Retrospectivos , Medição de Risco , Rituximab , Taxa de Sobrevida , Vincristina/administração & dosagem , Adulto JovemAssuntos
Infecções por HIV/complicações , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico , Adulto , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto JovemRESUMO
HLA-B27 transgenic animal models suggest a role for CD4(+) T lymphocytes in the pathogenesis of the spondyloarthropathies, and murine studies have raised the possibility that unusual forms of B27 may be involved in disease. We demonstrate that CD4(+) T cells capable of recognizing B27 can be isolated from humans by coculture with the MHC class II-negative cell line T2 transfected with B27. These CD4(+) T cells recognize a panel of B27-transfected cell lines that are defective in Ag-processing pathways, but not the nontransfected parental cell lines, in a CD4-dependent fashion. Inhibition of responses by the MHC class I-specific mAb w6/32 and the B27 binding mAb ME1 implicates the recognition of a form of B27 recognized by both of these Abs. We suggest that B27-reactive CD4(+) T cells may be pathogenic in spondyloarthropathies, particularly if factors such as infection influence expression of abnormal forms of B27.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Antígeno HLA-B27/metabolismo , Animais , Anticorpos Monoclonais , Linhagem Celular , Transformação Celular Viral , Técnicas de Cocultura , Antígeno HLA-B27/química , Antígeno HLA-B27/genética , Herpesvirus Humano 4 , Humanos , Camundongos , Camundongos Transgênicos , Espondiloartropatias/etiologia , Espondiloartropatias/genética , Espondiloartropatias/imunologia , Espondilite Anquilosante/imunologia , TransfecçãoRESUMO
Disseminated enteric human cytopathogenic orphan (echo) virus infection after allogeneic bone marrow transplantation has been reported once previously: a patient developed a fatal infection with the virus being isolated from brain, lung and heart. We report a second case of disseminated echovirus infection in which virus was isolated from the stomach and liver. On this occasion the infection was associated with the development of biopsy-proven acute graft-versus-host disease of the skin, stomach, colon and liver. The infection resolved without sequelae.
