RESUMO
OBJECTIVE: The Mannan-binding lectin (MBL) pathway involves recognition of fungal surfaces by MBL and cleavage of C2 and C4 by MBL-associated serine protease (namely, MASP-2). Recent data show that MBL pathway deficiency might result not only from polymorphisms of the MBL2 gene but also of MASP2. The aim of the study was to assess whether polymorphisms of these genes are associated with invasive fungal infections (IFIs) following allogeneic stem cell transplantation (allo-SCT). METHODS: The promoter and the exon 1 of MBL2 and the exon 3 of MASP2 were sequenced in 106 donor-recipient pairs from HLA-identical sibling allo-SCTs performed in a single institution. RESULTS: Ten percent of the donors and 11% of the recipients carried the MBL-low (O/O, LXA/O) genotypes; 7% of the donors and 3% of the recipients were heterozygous for the MASP2 Asp105Gly variant. Factors associated with a higher probability of IFIs were donor's MBL-low genotype (38% vs 12%, p = 0.01), recipient's MASP2 variant (67% vs 14%, p = 0.01), and acute graft-versus-host disease (GVHD) grades II to IV (27% vs 11%, p = 0.04); in the multivariate analysis MBL-low genotype (relative risk [RR] 7.3, p = 0.003), MASP2 variant (RR 6.4, p = 0.002), and acute GVHD II to IV (RR 3.8, p = 0.02) retained independent prognostic value. CONCLUSION: These results show for the first time that polymorphisms responsible for not only MBL but also MASP-2 deficiency are independent predictive factors for IFI after allo-SCT.
Assuntos
Lectina de Ligação a Manose da Via do Complemento/genética , Lectina de Ligação a Manose/genética , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Micoses/genética , Polimorfismo Genético , Transplante de Células-Tronco , Doença Aguda , Adulto , Complemento C2/genética , Complemento C2/metabolismo , Complemento C4/genética , Complemento C4/metabolismo , Análise Mutacional de DNA/métodos , Éxons/genética , Feminino , Predisposição Genética para Doença , Genótipo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/metabolismo , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/terapia , Humanos , Masculino , Lectina de Ligação a Manose/metabolismo , Serina Proteases Associadas a Proteína de Ligação a Manose/metabolismo , Pessoa de Meia-Idade , Micoses/etiologia , Micoses/metabolismo , Valor Preditivo dos Testes , Prognóstico , Regiões Promotoras Genéticas/genética , Transplante de Células-Tronco/efeitos adversos , Doadores de Tecidos , Transplante HomólogoRESUMO
Bortezomib is a potent and selective proteasome inhibitor recently introduced in the treatment of multiple myeloma (MM). This drug produces significant responses in about one-third of patients with relapsed/refractory disease. We first recognized the lack of efficacy of thalidomide in soft-tissue plasmacytomas. There is little information on the effect of bortezomib on extramedullary myeloma. Four of 23 patients treated with bortezomib at our institution had extramedullary involvement at the time of relapse. In three of these patients large soft-tissue plasmacytomas disappeared. This indicates that bortezomib may be useful in clinical situations of extramedullary disease in which other agents, such as thalidomide, may not be effective.
Assuntos
Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Pirazinas/uso terapêutico , Neoplasias de Tecidos Moles/tratamento farmacológico , Idoso , Antineoplásicos/administração & dosagem , Ácidos Borônicos/administração & dosagem , Bortezomib , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Inibidores de Proteases/administração & dosagem , Pirazinas/administração & dosagem , Recidiva , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologia , Resultado do TratamentoRESUMO
Infections are the main cause of death in neutropenic patients and are related to the degree and duration of neutropenia, the underlying disease, and the treatments received. To reduce the number of these infections, prophylactic strategies have been proposed. These strategies aim to prevent adquisition through contact, inhalation, or the gastrointestinal tract. Intestinal decontamination through fluoroquinolones has reduced Gram-negative infections but this strategy should not be used indiscriminately and should be reserved for high risk patients. Fluconazole as antifungal prophylaxis reduces mortality but does not modify the incidence of invasive aspergillosis. Cytomegalovirus infection should be prevented in patients with negative serology; in high risk patients with positive serology, monitoring and preemptive treatment with ganciclovir or foscarnet is recommended. Hematopoietic growth factors reduce the duration of neutropenia and could reduce mortality from infection.
Assuntos
Antibioticoprofilaxia , Neutropenia/microbiologia , Neutropenia/terapia , Infecções Oportunistas/prevenção & controle , Antifúngicos/uso terapêutico , Antivirais/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêuticoRESUMO
Las infecciones son la principal causa de muerte en los pacientes neutropénicos, en relación con el grado y la duración de la neutropenia, la enfermedad de base y los tratamientos recibidos. Para disminuir estas infecciones se han propuesto estrategias de profilaxis: medidas para evitar el contagio por contacto, por inhalación o por vía digestiva. Aunque la descontaminación intestinal con fluoroquinolonas ha reducido las infecciones por bacilos gramnegativos, no se recomienda su uso indiscriminado, sino reservar su utilización para pacientes de muy alto riesgo. El fluconazol como profilaxis antifúngica reduce la mortalidad, pero no modifica la incidencia de la aspergilosis invasiva. La infección por citomegalovirus debe prevenirse en los pacientes con serología negativa; en los que presentan una serología positiva con alto riesgo de enfermedad se recomienda la monitorización y el tratamiento anticipado con ganciclovir o foscarnet. Los factores de crecimiento hematopoyético reducen la duración de la neutropenia y podrían reducir la mortalidad de causa infecciosa
Infections are the main cause of death in neutropenic patients and are related to the degree and duration of neutropenia, the underlying disease, and the treatments received. To reduce the number of these infections, prophylactic strategies have been proposed. These strategies aim to prevent adquisition through contact, inhalation, or the gastrointestinal tract. Intestinal decontamination through fluoroquinolones has reduced Gram-negative infections but this strategy should not be used indiscriminately and should be reserved for high risk patients. Fluconazole as antifungal prophylaxis reduces mortality but does not modify the incidence of invasive aspergillosis. Cytomegalovirus infection should be prevented in patients with negative serology; in high risk patients with positive serology, monitoring and preemptive treatment with ganciclovir or foscarnet is recommended. Hematopoietic growth factors reduce the duration of neutropenia and could reduce mortality from infection