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Leukemia ; 32(6): 1427-1434, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29463830


Smoldering multiple myeloma (SMM) is a biologically heterogeneous, clinically defined entity with a variable rate of progression to symptomatic multiple myeloma (MM). Reliable markers for progression are critical for the development of potential therapeutic interventions. We retrospectively evaluated the predictive value of the evolving pattern of serum M-protein among other progression risk factors in 206 patients with SMM diagnosed between 1973 and 2012. Median time from recognition of evolving type to progression into symptomatic MM was 1.1 years (95% CI 0.5-2.0) and progression rate at 3 years was 71%. Development of the evolving type drastically worsened the prognostic estimation made at diagnosis for every covariate predictive of progression (serum M-protein size, bone marrow plasma cell infiltration, immunoparesis and Mayo Clinic risk). On average, the hazard ratio for progression to symptomatic MM increased to 5.1 (95% CI 3.4-7.6) after recognition of the evolving type. In conclusion, in patients with SMM the evolving pattern accurately predicts the risk of early progression to symptomatic disease, thereby allowing the identification of ultra-high risk patients who would be candidates for immediate therapy.

Proteínas do Mieloma/análise , Mieloma Múltiplo Latente/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Mieloma Múltiplo Latente/mortalidade
Ann Hematol ; 93(1): 107-11, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24218189


Heat-shock proteins (HSP) are important molecules in the pathogenesis of multiple myeloma (MM). Their blockages by drugs or cellular immune response have been investigated, and a possible association with the presence of oligoclonal bands (OB) has been postulated in patients with MM after allogenic stem cell transplantation. The aim of the present study was to ascertain the serum antibody levels against three HSP (60, 70 and 90) by ELISA in patients with MM in complete remission after autologous stem cell transplantation (ASCT), with or without OB, and compare them with those patients with stable gammopathy of undetermined significance (MGUS) and healthy controls. Our results in samples after ASCT showed no differential levels of anti-HSP according to the presence or absence of the oligoclonal response. However, higher levels of anti-HSP90 were found in patients with stable MGUS in comparison with MM patients (p = 0.004). In the same line, a longer progression-free survival was observed in those patients who presented higher anti-HSP90 levels after ASCT (p = 0.042). These results suggest, for first time, the potential of anti-HSP90 humoral immune response for long-term control of malignant plasma cell disorders.

Anticorpos Antineoplásicos/biossíntese , Autoanticorpos/biossíntese , Autoantígenos/biossíntese , Chaperonina 60/imunologia , Proteínas de Choque Térmico HSP70/imunologia , Proteínas de Choque Térmico HSP90/imunologia , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/imunologia , Proteínas de Neoplasias/imunologia , Bandas Oligoclonais/imunologia , Adulto , Idoso , Anticorpos Antineoplásicos/sangue , Anticorpos Antineoplásicos/imunologia , Especificidade de Anticorpos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Autoantígenos/sangue , Autoantígenos/imunologia , Ácidos Borônicos/administração & dosagem , Bortezomib , Terapia Combinada , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Glucocorticoides/administração & dosagem , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/imunologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Bandas Oligoclonais/sangue , Pirazinas/administração & dosagem , Indução de Remissão , Talidomida/administração & dosagem , Transplante Autólogo
Eur J Haematol ; 89(4): 340-4, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22690902


Limited data has been published on the treatment results in patients with light-chain deposition disease (LCDD). Whenever possible, high-dose melphalan followed by autologous stem cell transplantation (ASCT) has been the first treatment option, achieving somehow better results than conventional therapy. However, and based on the promising results obtained by treating patients with light-chain amyloidosis with bortezomib/dexamethasone, new treatment options appear in LCDD. Herein, we describe three patients with LCDD treated with bortezomib/dexamethasone followed by high-dose melphalan and autologous transplantation. We believe that this new approach should be the treatment of choice in this disease. In addition, those patients achieving hematologic complete response after ASCT could benefit from a kidney transplant if the renal impairment requiring dialysis persists.

Ácidos Borônicos/uso terapêutico , Dexametasona/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Pirazinas/uso terapêutico , Adulto , Ácidos Borônicos/administração & dosagem , Bortezomib , Terapia Combinada , Dexametasona/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/cirurgia , Pirazinas/administração & dosagem
Blood ; 113(22): 5370, 2009 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-19478048
Br J Haematol ; 130(5): 729-32, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16115129


Two variants of smoldering multiple myeloma (SMM) have been recognised: (i) an evolving type, characterised by a progressive increase in the M-protein size and short time to progression to overt multiple myeloma (MM) and (ii) a non-evolving type, with a long-lasting, stable M-protein and longer time to progression. Comparative genomic hybridisation (CGH) analyses in both subtypes of SMM (seven evolving and eight non-evolving SMM) were performed. Evolving SMM showed cytogenetic changes consistent with those found in de novo symptomatic MM (1q gains, chromosome 13 deletions) while the non-evolving variant showed no 1q gains and deletions were uncommon.

Cromossomos Humanos Par 13 , Mieloma Múltiplo/classificação , Proteínas do Mieloma/genética , Exame de Medula Óssea , Aberrações Cromossômicas , Progressão da Doença , Deleção de Genes , Humanos , Hibridização in Situ Fluorescente , Interfase , Mieloma Múltiplo/genética , Prognóstico
Haematologica ; 89(7): 832-6, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15257935


BACKGROUND AND OBJECTIVES: Thalidomide is an antiangiogenic drug that produces a response rate ranging from 32 to 64% in patients with refractory/relapsed multiple myeloma (MM). However, the efficacy of thalidomide in patients with soft-tissue plasmacytomas is controversial. The aim of this study was to assess the response rate to thalidomide in patients with advanced MM and to correlate the response rate with the presence of extramedullary involvement. DESIGN AND METHODS: Thirty-eight patients with refractory/relapsed MM were treated with thalidomide. Eleven patients had extramedullary involvement when therapy was initiated. The response rate was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation. RESULTS: Sixteen of the 38 patients (42%) responded to thalidomide. The response rate was significantly higher in patients without extramedullary involvement (59% vs 0%, p=0.0006). Although four of the 11 patients with extramedullary involvement had a serological response, a progression of the soft-tissue masses was observed in all of them. INTERPRETATION AND CONCLUSIONS: Thalidomide is effective in patients with advanced MM. However, extramedullary disease does not respond to thalidomide, as delivered in this series. The mechanisms to explain different response to therapy depending on tumor homing warrant further investigation.

Inibidores da Angiogênese/uso terapêutico , Neoplasias da Medula Óssea/tratamento farmacológico , Mieloma Múltiplo/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Talidomida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Medula Óssea/patologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Invasividade Neoplásica , Neoplasias de Tecidos Moles/patologia