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[PMID]:29181840
[Au] Autor:Treon SP; Gustine J; Xu L; Manning RJ; Tsakmaklis N; Demos M; Meid K; Guerrera ML; Munshi M; Chan G; Chen J; Kofides A; Patterson CJ; Yang G; Liu X; Severns P; Dubeau T; Hunter ZR; Castillo JJ
[Ad] Endereço:Bing Center for Waldenstrom's Macroglobulinemia, Dana Farber Cancer Institute, Boston, MA, USA.
[Ti] Título:MYD88 wild-type Waldenstrom Macroglobulinaemia: differential diagnosis, risk of histological transformation, and overall survival.
[So] Source:Br J Haematol;180(3):374-380, 2018 02.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:MYD88 mutations are present in 95% of Waldenstrom Macroglobulinaemia (WM) patients, and support diagnostic discrimination from other IgM-secreting B-cell malignancies. Diagnostic discrimination can be difficult among suspected wild-type MYD88 (MYD88 ) WM cases. We systematically reviewed the clinical, pathological and laboratory studies for 64 suspected MYD88 WM patients. World Health Organization and WM consensus guidelines were used to establish clinicopathological diagnosis. Up to 30% of suspected MYD88 WM cases had an alternative clinicopathological diagnosis, including IgM multiple myeloma. The estimated 10-year survival was 73% (95% confidence interval [CI] 52-86%) for MYD88 versus 90% (95% CI 82-95%) for mutated (MYD88 ) WM patients (Log-rank P < 0·001). Multivariate analysis only showed MYD88 mutation status (P < 0·001) as a significant determinant for overall survival. Diffuse large B-cell lymphoma (DLBCL) was diagnosed in 7 (15·2%) and 2 (0·76%) of MYD88 and MYD88 patients, respectively (Odds ratio 23·3; 95% CI 4·2-233·8; P < 0·001). Overall survival was shorter among MYD88 patients with an associated DLBCL event (Log-rank P = 0·08). The findings show that among suspected MYD88 WM cases, an alternative clinicopathological diagnosis is common and can impact clinical care. WM patients with MYD88 disease have a high incidence of associated DLBCL events and significantly shorter survival versus those with MYD88 disease.
[Mh] Termos MeSH primário: Fator 88 de Diferenciação Mieloide/genética
Macroglobulinemia de Waldenstrom/diagnóstico
Macroglobulinemia de Waldenstrom/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Biomarcadores
Medula Óssea/patologia
Transformação Celular Neoplásica
Análise Mutacional de DNA
Diagnóstico Diferencial
Feminino
Genótipo
Seres Humanos
Imunofenotipagem
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Mutação
Prognóstico
Modelos de Riscos Proporcionais
Macroglobulinemia de Waldenstrom/mortalidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (MYD88 protein, human); 0 (Myeloid Differentiation Factor 88)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.15049


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[PMID]:27776353
[Au] Autor:Wu J; Zhang M; Liu D
[Ad] Endereço:Department of Oncology, The first Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
[Ti] Título:Bruton tyrosine kinase inhibitor ONO/GS-4059: from bench to bedside.
[So] Source:Oncotarget;8(4):7201-7207, 2017 Jan 24.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been approved for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Acquired resistance to ibrutinib due to BTK C481S mutation has been reported. Mutations in PLCγ2 can also mediate resistance to ibrutinib. Untoward effects due to off-target effects are also disadvantages of ibrutinib. More selective and potent BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being investigated. This review summarized the preclinical research and clinical data of ONO/GS-4059.
[Mh] Termos MeSH primário: Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Imidazóis/uso terapêutico
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Linfoma de Célula do Manto/tratamento farmacológico
Pirimidinas/uso terapêutico
Macroglobulinemia de Waldenstrom/tratamento farmacológico
[Mh] Termos MeSH secundário: Ensaios Clínicos como Assunto
Seres Humanos
Imidazóis/farmacologia
Leucemia Linfocítica Crônica de Células B/genética
Linfoma de Célula do Manto/genética
Mutação
Fosfolipase C gama/genética
Proteínas Tirosina Quinases/antagonistas & inibidores
Proteínas Tirosina Quinases/genética
Pirimidinas/farmacologia
Resultado do Tratamento
Macroglobulinemia de Waldenstrom/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (GS-4059); 0 (Imidazoles); 0 (Pyrimidines); EC 2.7.10.1 (Agammaglobulinaemia tyrosine kinase); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 3.1.4.3 (Phospholipase C gamma)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.12786


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[PMID]:29353304
[Au] Autor:Jiménez C; Prieto-Conde MI; García-Álvarez M; Alcoceba M; Escalante F; Chillón MDC; García de Coca A; Balanzategui A; Cantalapiedra A; Aguilar C; Corral R; González-López T; Marín LA; Bárez A; Puig N; García-Mateo A; Gutiérrez NC; Sarasquete ME; González M; García-Sanz R
[Ad] Endereço:Hematology Department, University Hospital of Salamanca and Research Biomedical Institute of Salamanca (IBSAL), Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
[Ti] Título:Unraveling the heterogeneity of IgM monoclonal gammopathies: a gene mutational and gene expression study.
[So] Source:Ann Hematol;97(3):475-484, 2018 Mar.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Immunoglobulin M (IgM) monoclonal gammopathies show considerable variability, involving three different stages of presentation: IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), asymptomatic Waldenström's macroglobulinemia (AWM), and symptomatic WM (SWM). Despite recent findings about the genomic and transcriptomic characteristics of such disorders, we know little about the causes of this clinical heterogeneity or the mechanisms involved in the progression from indolent to symptomatic forms. To clarify these matters, we have performed a gene expression and mutational study in a well-characterized cohort of 69 patients, distinguishing between the three disease presentations in an attempt to establish the relationship with the clinical and biological features of the patients. Results showed that the frequency of genetic alterations progressively increased from IgM-MGUS to AWM and SWM. This means that, in contrast to MYD88 p.L265P and CXCR4 WHIM mutations, present from the beginning of the pathogenesis, most of them would be acquired during the course of the disease. Moreover, the expression study revealed a higher level of expression of genes belonging to the Toll-like receptor (TLR) signaling pathway in symptomatic versus indolent forms, which was also reflected in the disease presentation and prognosis. In conclusion, our findings showed that IgM monoclonal gammopathies present higher mutational burden as the disease progresses, in parallel to the upregulation of relevant pathogenic pathways. This study provides a translational view of the genomic basis of WM pathogenesis.
[Mh] Termos MeSH primário: Heterogeneidade Genética
Imunoglobulina M/genética
Gamopatia Monoclonal de Significância Indeterminada/genética
Macroglobulinemia de Waldenstrom/genética
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Análise Mutacional de DNA
Progressão da Doença
Feminino
Perfilação da Expressão Gênica
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Masculino
Meia-Idade
Gamopatia Monoclonal de Significância Indeterminada/patologia
Prognóstico
Macroglobulinemia de Waldenstrom/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunoglobulin M)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180122
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3207-3


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[PMID]:29173973
[Au] Autor:Gauthier J; Chantepie S; Bouabdallah K; Jost E; Nguyen S; Gac AC; Damaj G; Duléry R; Michallet M; Delage J; Lewalle P; Morschhauser F; Salles G; Yakoub-Agha I; Cornillon J
[Ad] Endereço:CHRU de Lille, pôle spécialités médicales et gérontologie, service des maladies du sang, secteur allogreffe de cellules souches hématopoïétiques, 59037 Lille, France; Université de Lille, UFR médecine, 59000 Lille, France.
[Ti] Título:[Allogeneic haematopoietic cell transplantation for indolent lymphomas: Guidelines from the Francophone Society Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].
[Ti] Título:Allogreffe de cellules souches hématopoïétiques dans les lymphomes indolents : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)..
[So] Source:Bull Cancer;104(12S):S121-S130, 2017 Dec.
[Is] ISSN:1769-6917
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic hematopoietic cell transplantation is a potentially curative option, this is true particularly the case of relapse after autologous stem cell transplantation. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic hematopoietic cell transplantation for relapsed or refractory lymphoma. During the 2016 annual workshop of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), we performed a comprehensive review of the literature published in the last 10 years and established guidelines to clarify the indications and transplant modalities in this setting. This paper specifically reports on our conclusions regarding indolent lymphomas, mainly follicular lymphoma and chronic lymphocytic leukemia.
[Mh] Termos MeSH primário: Transplante de Células-Tronco Hematopoéticas/normas
Leucemia Linfocítica Crônica de Células B/terapia
Linfoma Folicular/terapia
Linfoma de Célula do Manto/terapia
Macroglobulinemia de Waldenstrom/terapia
[Mh] Termos MeSH secundário: Algoritmos
Aloenxertos
Tomada de Decisões
França
Seres Humanos
Recidiva
Sociedades Médicas
[Pt] Tipo de publicação:CONSENSUS DEVELOPMENT CONFERENCE; JOURNAL ARTICLE; PRACTICE GUIDELINE; REVIEW
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171228
[Lr] Data última revisão:
171228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


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[PMID]:28786474
[Au] Autor:Paludo J; Abeykoon JP; Kumar S; Shreders A; Ailawadhi S; Gertz MA; Kourelis T; King RL; Reeder CB; Leung N; Kyle RA; Buadi FK; Habermann TM; Dingli D; Witzig TE; Dispenzieri A; Lacy MQ; Go RS; Lin Y; Gonsalves WI; Warsame R; Lust JA; Rajkumar SV; Ansell SM; Kapoor P
[Ad] Endereço:Division of Hematology, Mayo Clinic, Rochester, MN, USA.
[Ti] Título:Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-naïve patients with Waldenstrom macroglobulinemia.
[So] Source:Br J Haematol;179(1):98-105, 2017 Oct.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88 genotype. Herein, we additionally report on the activity of DRC based on the MYD88 mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87%. The median progression-free survival (PFS) and time-to-next-therapy (TTNT) were 32 (95% confidence interval [CI]: 15-51) and 50 (95% CI: 35-60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23-not reached [NR]) and NR (95% CI: 37-NR), respectively. Twenty-five (86%) of 29 genotyped patients harbored MYD88 . The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients' MYD88 status.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Macroglobulinemia de Waldenstrom/diagnóstico
Macroglobulinemia de Waldenstrom/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Biomarcadores
Ciclofosfamida/administração & dosagem
Dexametasona/administração & dosagem
Gerenciamento Clínico
Resistência a Medicamentos Antineoplásicos
Feminino
Seres Humanos
Masculino
Meia-Idade
Mutação
Fator 88 de Diferenciação Mieloide/genética
Recidiva
Retratamento
Rituximab/administração & dosagem
Terapia de Salvação
Análise de Sobrevida
Resultado do Tratamento
Macroglobulinemia de Waldenstrom/mortalidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Biomarkers); 0 (Myeloid Differentiation Factor 88); 4F4X42SYQ6 (Rituximab); 7S5I7G3JQL (Dexamethasone); 8N3DW7272P (Cyclophosphamide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14826


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[PMID]:28770576
[Au] Autor:Durot E; Tomowiak C; Michallet AS; Dupuis J; Hivert B; Leprêtre S; Toussaint E; Godet S; Merabet F; Van Den Neste E; Ivanoff S; Roussel X; Zini JM; Regny C; Lemal R; Sutton L; Perrot A; Le Dû K; Kanagaratnam L; Morel P; Leblond V; Delmer A
[Ad] Endereço:Department of Haematology, University Hospital of Reims and UFR Médecine, Reims, France.
[Ti] Título:Transformed Waldenström macroglobulinaemia: clinical presentation and outcome. A multi-institutional retrospective study of 77 cases from the French Innovative Leukemia Organization (FILO).
[So] Source:Br J Haematol;179(3):439-448, 2017 Nov.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a rare and poorly reported complication of Waldenström macroglobulinaemia (WM). We performed a retrospective study of 77 WM patients with biopsy-proven transformation to DLBCL. The median time from WM diagnosis to HT was 4·6 years and 16 patients (21%) had never been treated for WM. At HT, extranodal sites were observed in 91% of patients with a rather high incidence of central nervous system, cutaneous or testicular involvement. Fluorodeoxyglucose-positron emission tomography was performed in half of the patients and the median maximum standardized uptake value was 15 for transformed disease. More than 80% of cases with available data for assessment by the Hans' algorithm harboured a non-germinal centre B-cell phenotype. First-line treatment for transformation consisted of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-like regimen in 85% of patients. The overall response rate after first-line treatment was 61% and the median overall survival was only 16 months for the entire cohort. Time to transformation above 5 years (P = 0·0004) and elevated LDH (P = 0·02) were associated with worse outcome. Based on these findings, HT should be considered and lead to a biopsy in WM patients presenting with extranodal involvement, elevated LDH and constitutional symptoms. The optimal therapeutic approaches remain to be defined.
[Mh] Termos MeSH primário: Transformação Celular Neoplásica/patologia
Linfoma Difuso de Grandes Células B/patologia
Macroglobulinemia de Waldenstrom/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Anticorpos Monoclonais Murinos/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Biomarcadores Tumorais/sangue
Biópsia
Ciclofosfamida/uso terapêutico
Doxorrubicina/uso terapêutico
Feminino
Fluordesoxiglucose F18
Seres Humanos
L-Lactato Desidrogenase/sangue
Linfoma Difuso de Grandes Células B/diagnóstico por imagem
Linfoma Difuso de Grandes Células B/tratamento farmacológico
Masculino
Meia-Idade
Tomografia por Emissão de Pósitrons/métodos
Prednisona/uso terapêutico
Prognóstico
Estudos Retrospectivos
Fatores de Risco
Análise de Sobrevida
Tomografia Computadorizada por Raios X
Resultado do Tratamento
Vincristina/uso terapêutico
Macroglobulinemia de Waldenstrom/diagnóstico por imagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Murine-Derived); 0 (Biomarkers, Tumor); 0 (R-CHOP protocol); 0Z5B2CJX4D (Fluorodeoxyglucose F18); 5J49Q6B70F (Vincristine); 80168379AG (Doxorubicin); 8N3DW7272P (Cyclophosphamide); EC 1.1.1.27 (L-Lactate Dehydrogenase); VB0R961HZT (Prednisone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14881


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[PMID]:28723285
[Au] Autor:Hrabak-Paar M; Kralik M
[Ad] Endereço:From the Department of Diagnostic and Interventional Radiology, University Hospital Center Zagreb, University of Zagreb School of Medicine, Kispaticeva 12, HR-10000 Zagreb, Croatia (M.H.P., M.K.); and Clinic of Radiology and Nuclear Medicine, University of Basel Hospital, Basel, Switzerland (M.H.P.).
[Ti] Título:Case 244: Systemic Amyloidosis-A Complication of Waldenström Macroglobulinemia.
[So] Source:Radiology;284(2):597-602, 2017 Aug.
[Is] ISSN:1527-1315
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:History A 68-year-old man was admitted to the hospital for work-up because of generalized fatigue, anorexia, chronic diarrhea, and weight loss. Laboratory work-up revealed an erythrocyte sedimentation rate of 58 mm/h (reference range, 3-23 mm/h), a hemoglobin level of 14.1 g/dL (reference range, 13.8-17.5 g/dL), a leukocyte count of 8.1 × 10 /L (reference range, [3.4-9.7] × 10 /L), a platelet count of 223 × 10 /L (reference range, [158-424] × 10 /L), an alkaline phosphatase level of 85 U/L (1.42 µkat/L) (normal level, <142 U/L [2.37 µkat/L]), a serum creatinine level of 93 µmol/L (reference range, 79-125 µmol/L), a serum total protein level of 82 g/L (reference range, 66-81 g/L), a serum albumin level of 39.3 g/L (reference range, 40.2-47.6 g/L), an albumin-to-globulin ratio (a test showing relative amounts of major plasma proteins) of 0.92 (reference range, 0.8-2.0), a urine protein level of 15 mg/dL (normal level, <20 mg/dL), a total serum calcium level of 2.46 mmol/L (reference range, 2.14-2.53 mmol/L), and a carcinoembryonic antigen value of 2.69 µg/L (normal value, <3.4 µg/L). Serology findings were negative for celiac disease. Thyroid function was normal, as were 5-hydroxyindoleacetic acid and chromogranin A levels. Initial radiologic examination included chest radiography and plain abdominal erect radiography. Gastrointestinal endoscopy was performed to rule out inflammatory bowel disease or gastrointestinal neoplasm as a cause of chronic diarrhea. Endoscopic mucosal resection of two polyps from the cardia and duodenal bulb was performed during esophagogastroduodenoscopy, but histologic findings at hematoxylin-eosin staining were normal. Colonoscopy revealed diverticulosis involving the entire colon. Serum immunoelectrophoresis showed a monoclonal band, which was confirmed to be immunoglobulin Mλ at immunofixation. After histologic analysis of the bone marrow biopsy specimen, diagnosis of Waldenström macroglobulinemia was established, and computed tomography (CT) of the thorax, abdomen, and pelvis was requested to depict lymphadenopathy and organomegaly. On the basis of CT findings, two more specimens considered highly sensitive for the CT diagnosis were obtained via minimally invasive biopsy, but the results were negative. Magnetic resonance (MR) imaging was performed a year later to control the progression of CT findings.
[Mh] Termos MeSH primário: Amiloidose/diagnóstico por imagem
Amiloidose/etiologia
Macroglobulinemia de Waldenstrom/complicações
Macroglobulinemia de Waldenstrom/diagnóstico por imagem
[Mh] Termos MeSH secundário: Idoso
Biópsia
Vermelho Congo
Meios de Contraste
Diagnóstico Diferencial
Seres Humanos
Masculino
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Contrast Media); 3U05FHG59S (Congo Red)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1148/radiol.2017151156


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[PMID]:28677830
[Au] Autor:Olszewski AJ; Chen C; Gutman R; Treon SP; Castillo JJ
[Ad] Endereço:Department of Medicine, Brown University Warren Alpert Medical School, Providence, RI, USA.
[Ti] Título:Comparative outcomes of immunochemotherapy regimens in Waldenström macroglobulinaemia.
[So] Source:Br J Haematol;179(1):106-115, 2017 Oct.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Comparative data on immunochemotherapy regimens for Waldenström macroglobulinaemia/lymphoplasmacytic lymphoma (WM/LPL) are lacking. We analysed overall survival (OS), risk of hospitalizations, transfusions and plasmapheresis in a population-based cohort of patients ≥65 years old initiating WM/LPL therapy in 1999-2013. To minimize bias, we applied a propensity score-based causal inference method. We conducted three analyses of: patients treated with or without rituximab, patients treated with rituximab monotherapy or with combination immunochemotherapy, and regimens based on classic purine analogues or alkylators. Among 1310 patients, 78·5% received rituximab. Patients who received rituximab had significantly better OS [hazard ratio (HR) 0·62, 95% confidence interval (CI) 0·55-0·71] and lower risk of transfusions (risk difference -3·3%, 95% CI -6·3 to -0·3) than those who did not, without a significant difference in hospitalizations or plasmapheresis. We observed no significant difference in OS (HR 0·91, 95% CI 0·79-1·04) between rituximab monotherapy and combination immunochemotherapy, but toxicity outcomes were lower with rituximab alone. Neither survival (HR 1·10, 95%CI 0·92-1·32) nor toxicity outcomes differed significantly between regimens based on purine analogues or alkylators. The survival advantage strongly supports rituximab as part of upfront therapy for WM/LPL, whereas regimens with either purine analogues or alkylating agents result in similar outcomes.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Macroglobulinemia de Waldenstrom/tratamento farmacológico
Macroglobulinemia de Waldenstrom/epidemiologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Comorbidade
Feminino
Seres Humanos
Imunoterapia
Estimativa de Kaplan-Meier
Masculino
Vigilância da População
Fatores de Risco
Rituximab/administração & dosagem
Programa de SEER
Resultado do Tratamento
Macroglobulinemia de Waldenstrom/mortalidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
4F4X42SYQ6 (Rituximab)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170706
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14828


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[PMID]:28617062
[Au] Autor:Castillo JJ; Hunter ZR; Yang G; Treon SP
[Ad] Endereço:a Bing Center for Waldenström Macroglobulinemia , Dana-Farber Cancer Institute, Harvard Medical School , Boston , MA , USA.
[Ti] Título:Novel approaches to targeting MYD88 in Waldenström macroglobulinemia.
[So] Source:Expert Rev Hematol;10(8):739-744, 2017 Aug.
[Is] ISSN:1747-4094
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Waldenström macroglobulinemia (WM) is an incurable lymphoma characterized by the accumulation of IgM-producing lymphoplasmacytic cells in the bone marrow and other organs. Although WM patients can experience prolonged remissions, the disease invariably recurs advocating for the need of novel treatments in order to achieve higher response and survival rates. The discovery of a recurrent mutation in the MYD88 gene and an increased understanding behind the biology of MYD88 signaling have provided the opportunity to developing novel agents targeting the MYD88 pathway. Areas covered: The present review focuses on potential therapies that could change the landscape of treatment of patients with WM, specifically focusing on inhibitors of the Bruton tyrosine kinase (BTK), phosphatidylinositol-3 kinase, hematopoietic cell kinase, interleukin-1 receptor associated kinase and MYD88 assembly. Expert commentary: Novel agents such as the BTK inhibitor ibrutinib has shown to be safe and highly effective in the treatment of WM. Ibrutinib has been approved in Europe and the United States for its use in patients with symptomatic WM. Prospective studies are ongoing and/or planned to study many other novel agents alone and in combination with aims at improving response, survival and quality of life in patients with WM.
[Mh] Termos MeSH primário: Terapia de Alvo Molecular
Fator 88 de Diferenciação Mieloide/antagonistas & inibidores
Macroglobulinemia de Waldenstrom/tratamento farmacológico
Macroglobulinemia de Waldenstrom/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores
Quinases Associadas a Receptores de Interleucina-1/genética
Quinases Associadas a Receptores de Interleucina-1/metabolismo
Mutação
Fator 88 de Diferenciação Mieloide/genética
Fator 88 de Diferenciação Mieloide/metabolismo
Fosfatidilinositol 3-Quinases/antagonistas & inibidores
Fosfatidilinositol 3-Quinases/genética
Fosfatidilinositol 3-Quinases/metabolismo
Ligação Proteica
Inibidores de Proteínas Quinases/farmacologia
Inibidores de Proteínas Quinases/uso terapêutico
Multimerização Proteica/efeitos dos fármacos
Proteínas Tirosina Quinases/antagonistas & inibidores
Proteínas Tirosina Quinases/genética
Proteínas Tirosina Quinases/metabolismo
Proteínas Proto-Oncogênicas c-hck/antagonistas & inibidores
Proteínas Proto-Oncogênicas c-hck/genética
Proteínas Proto-Oncogênicas c-hck/metabolismo
Transdução de Sinais/efeitos dos fármacos
Receptores Toll-Like/antagonistas & inibidores
Receptores Toll-Like/metabolismo
Macroglobulinemia de Waldenstrom/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Myeloid Differentiation Factor 88); 0 (Protein Kinase Inhibitors); 0 (Toll-Like Receptors); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.10.1 (Agammaglobulinaemia tyrosine kinase); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.2 (Proto-Oncogene Proteins c-hck); EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170616
[St] Status:MEDLINE
[do] DOI:10.1080/17474086.2017.1343661


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[PMID]:28592170
[Au] Autor:Benevolo G; Nicolosi M; Santambrogio E; Vitolo U
[Ad] Endereço:a Division of Hematology , AOU Città della Salute e della Scienza , Torino , Italy.
[Ti] Título:Current options to manage Waldenström's macroglobulinemia.
[So] Source:Expert Rev Hematol;10(7):637-647, 2017 Jul.
[Is] ISSN:1747-4094
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Waldenström's macroglobulinemia (WM) is a rare, incurable B-cell lymphoma, with a median survival of 5-10 years in symptomatic patients. There is no consensus on the standard of care and several agents are currently used in these patients. Areas covered: In this article, we will review the use of standard therapies and new drugs investigated such as monoclonal antibodies, proteasome inhibitors, immunomodulatory agents, Bruton's tyrosine kinase inhibitors and novel agents in early-stage development. Expert commentary: RCD (Rituximab/Cyclophosphamide/Dexamethasone) is an effective and safe treatment in first line in WM. BR (Bendamustine/Rituximab) or BRD (Bortezomib/Rituximab/Dexamethasone) provide durable responses, and are still indicated in most patients. Ibrutinib is a new option and it was approved as primary therapy and for relapse. Carfilzomib based therapy represents an emerging option for proteasome-inhibitor based therapy for WM. Despite encouraging results, WM remains an incurable disease; therefore, new treatment options are needed. For this reason, continued participation in clinical trials should be encouraged.
[Mh] Termos MeSH primário: Macroglobulinemia de Waldenstrom/diagnóstico
Macroglobulinemia de Waldenstrom/terapia
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/administração & dosagem
Anticorpos Monoclonais/uso terapêutico
Antineoplásicos/administração & dosagem
Antineoplásicos/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Terapia Combinada
Gerenciamento Clínico
Resistência a Medicamentos
Transplante de Células-Tronco Hematopoéticas
Seres Humanos
Fatores Imunológicos/uso terapêutico
Terapia de Alvo Molecular
Prognóstico
Inibidores de Proteínas Quinases/uso terapêutico
Recidiva
Medição de Risco
Transplante Autólogo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antineoplastic Agents); 0 (Immunologic Factors); 0 (Protein Kinase Inhibitors)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170609
[St] Status:MEDLINE
[do] DOI:10.1080/17474086.2017.1339596



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