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[PMID]:28453705
[Au] Autor:Mato AR; Hill BT; Lamanna N; Barr PM; Ujjani CS; Brander DM; Howlett C; Skarbnik AP; Cheson BD; Zent CS; Pu JJ; Kiselev P; Foon K; Lenhart J; Henick Bachow S; Winter AM; Cruz AL; Claxton DF; Goy A; Daniel C; Isaac K; Kennard KH; Timlin C; Fanning M; Gashonia L; Yacur M; Svoboda J; Schuster SJ; Nabhan C
[Ad] Endereço:Center for CLL, Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA.
[Ti] Título:Optimal sequencing of ibrutinib, idelalisib, and venetoclax in chronic lymphocytic leukemia: results from a multicenter study of 683 patients.
[So] Source:Ann Oncol;28(5):1050-1056, 2017 05 01.
[Is] ISSN:1569-8041
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Ibrutinib, idelalisib, and venetoclax are approved for treating CLL patients in the United States. However, there is no guidance as to their optimal sequence. Patients and methods: We conducted a multicenter, retrospective analysis of CLL patients treated with kinase inhibitors (KIs) or venetoclax. We examined demographics, discontinuation reasons, overall response rates (ORR), survival, and post-KI salvage strategies. Primary endpoint was progression-free survival (PFS). Results: A total of 683 patients were identified. Baseline characteristics were similar in the ibrutinib and idelalisib groups. ORR to ibrutinib and idelalisib as first KI was 69% and 81%, respectively. With a median follow-up of 17 months (range 1-60), median PFS and OS for the entire cohort were 35 months and not reached. Patients treated with ibrutinib (versus idelalisib) as first KI had a significantly better PFS in all settings; front-line [hazard ratios (HR) 2.8, CI 1.3-6.3, P = 0.01], relapsed-refractory (HR 2.8, CI 1.9-4.1, P < 0.001), del17p (HR 2.0, CI 1.2-3.4, P = 0.008), and complex karyotype (HR 2.5, CI 1.2-5.2, P = 0.02). At the time of initial KI failure, use of an alternate KI or venetoclax had a superior PFS when compared with chemoimmunotherapy. Furthermore, patients who discontinued ibrutinib due to progression or toxicity had marginally improved outcomes if they received venetoclax (ORR 79%) versus idelalisib (ORR 46%) (PFS HR .6, CI.3-1.0, P = 0.06). Conclusions: In the largest real-world experience of novel agents in CLL, ibrutinib appears superior to idelalisib as first KI. Furthermore, in the setting of KI failure, alternate KI or venetoclax therapy appear superior to chemoimmunotherapy combinations. The use of venetoclax upon ibrutinib failure might be superior to idelalisib. These data support the need for trials testing sequencing strategies to optimize treatment algorithms.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem
Intervalo Livre de Doença
Esquema de Medicação
Seres Humanos
Estimativa de Kaplan-Meier
Leucemia Linfocítica Crônica de Células B/mortalidade
Meia-Idade
Modelos de Riscos Proporcionais
Purinas/administração & dosagem
Pirazóis/administração & dosagem
Pirimidinas/administração & dosagem
Quinazolinonas/administração & dosagem
Estudos Retrospectivos
Sulfonamidas/administração & dosagem
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Bridged Bicyclo Compounds, Heterocyclic); 0 (PCI 32765); 0 (Purines); 0 (Pyrazoles); 0 (Pyrimidines); 0 (Quinazolinones); 0 (Sulfonamides); N54AIC43PW (venetoclax); YG57I8T5M0 (idelalisib)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/annonc/mdx031


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[PMID]:29299750
[Au] Autor:Wang WT; Zhu HY; Wu YJ; Xia Y; Wu JZ; Wu W; Liang JH; Wang L; Fan L; Li JY; Xu W
[Ad] Endereço:Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.
[Ti] Título:Elevated absolute NK cell counts in peripheral blood predict good prognosis in chronic lymphocytic leukemia.
[So] Source:J Cancer Res Clin Oncol;144(3):449-457, 2018 Mar.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The aim of this study was to investigate the prognostic significance of the absolute natural killer (NK) cell counts in peripheral blood in patients with chronic lymphocytic leukemia (CLL). METHODS: A total of 273 previously untreated patients with CLL from April 2004 and October 2015 were enrolled into this retrospective study. We analysed the T cell subsets of all patients and figured out the number of NK cells. Comparisons of NK cell count as continuous parameter in different groups were described using Mann-Whitney U test and the Kruskal-Wallis test. Kaplan-Meier method was used to survival analysis, and the Cox proportional hazards models were used for the estimation of prognostic factors. RESULTS: NK cell counts were calculated in 273 therapy-naive CLL patients, and higher number of NK cell was observed in those with Binet stage A/B, ZAP-70 < 20%, normal serum albumin and ß -microglobulin levels. Using a NK cell count cut-off of 0.40 × 10 /L, patients with lower NK cell count (< 0.40 × 10 /L) had a significantly shorter overall survival (OS) than those with higher NK cell count (≥ 0.40 × 10 /L) (P = 0.0014). Multivariate analysis showed that NK cell counts remained its prognostic value. However, the effect of NK cell count on time to treatment was not significant. CONCLUSIONS: Our results suggest that NK cell count is an independent prognostic marker for OS in patients with CLL and NK cell counts ≥ 0.40 × 10 /L can routinely be used to identify patients with favorable survival.
[Mh] Termos MeSH primário: Células Matadoras Naturais/patologia
Leucemia Linfocítica Crônica de Células B/diagnóstico
Leucemia Linfocítica Crônica de Células B/imunologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Seres Humanos
Leucemia Linfocítica Crônica de Células B/mortalidade
Leucemia Linfocítica Crônica de Células B/patologia
Contagem de Linfócitos
Masculino
Meia-Idade
Prognóstico
Estudos Retrospectivos
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180105
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2568-2


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[PMID]:29284783
[Au] Autor:Gordiienko I; Shlapatska L; Kholodniuk VM; Kovalevska L; Ivanivskaya TS; Sidorenko SP
[Ad] Endereço:Department of Molecular and Cellular Pathobiology, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
[Ti] Título:CD150 and CD180 are involved in regulation of transcription factors expression in chronic lymphocytic leukemia cells.
[So] Source:Exp Oncol;39(4):291-298, 2017 Dec.
[Is] ISSN:1812-9269
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sequential stages of B-cell development is stringently coordinated by transcription factors (TFs) network that include B-lineage commitment TFs (Ikaros, Runx1/Cbfb, E2A, and FOXO1), B-lineage maintenance TFs (EBF1 and PAX5) and stage specific set of TFs (IRF4, IRF8, BCL6, BLIMP1). Deregulation of TFs expression and activity is often occurs in malignant B cells. The aim of this study was to evaluate TFs expression in chronic lymphocytic leukemia cells taking into consideration CD150 cell surface expression. From other side we attempted to regulate TFs expression via CD150 and CD180 cell surface receptors. MATERIALS AND METHODS: Studies were performed on normal peripheral blood B-cell subpopulations and chronic lymphocytic leukemia (CLL) cells isolated from peripheral blood of 67 primary untreated patients with CLL. Evaluation of TFs expression was performed on mRNA level using qRT-PCR and on protein level by western blot analysis. RESULTS: Median of PAX5 and EBF1 mRNA expression was higher in cell surface CD150 positive (csCD150 ) compared to csCD150 CLL cases or normal CD19 and CD19 CD5 B-cell subsets. Differences in mRNA expression of IRF8, IRF4 and BLIMP1 between studied groups of CLL and normal B cells were not revealed. All CLL cases were characterized by downregulated expression of PU.1 and BCL6 mRNAs in comparison to normal B cells. At the same time elevated SPIB mRNA expression level was restricted to CLL cells. Protein expression of IRF4, IRF8 and BCL6 was uniformly distributed between csCD150 and csCD150 CLL cases. PU.1 protein and CD20 that is direct PU.1 target gene positively correlated with CD150 cell surface expression on CLL cells. Ligation of CD150 and CD180 alone or in combination upregulated IRF8 and PU.1 while downregulated the IRF4 mRNA expression. Signaling via CD150 or CD180 alone elevated the level of BCL6 mRNA. Strong downregulation of IRF4 mRNA was observed after CD150, CD180 or CD150 andCD180 coligation on CLL cells. We found that in CLL cells CD150 is a negative regulator of SPIB while CD180 is involved in upregulation of EBF1 expression level. Moreover, CD180 ligation on CLL cells caused increase of CD150 mRNA level that is a one of the EBF1 target genes. CONCLUSIONS: Analysis of TFs expression profile revealed upregulated SPIB mRNA level and downregulated PU.1 in CLL cells. CD150 and CD180 receptors may modulate transcriptional program in CLL cells by regulating the TFs expression levels.
[Mh] Termos MeSH primário: Antígenos CD/metabolismo
Regulação Neoplásica da Expressão Gênica/fisiologia
Leucemia Linfocítica Crônica de Células B/metabolismo
Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo
Fatores de Transcrição/biossíntese
[Mh] Termos MeSH secundário: Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (CD180 protein, human); 0 (SLAMF1 protein, human); 0 (Transcription Factors); 169535-43-7 (Signaling Lymphocytic Activation Molecule Family Member 1)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171230
[St] Status:MEDLINE


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[PMID]:29284776
[Au] Autor:Matveeva A; Kovalevska L; Kholodnyuk I; Ivanivskaya T; Kashuba E
[Ad] Endereço:R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
[Ti] Título:The TGF-beta - SMAD pathway is inactivated in cronic lymphocytic leukemia cells.
[So] Source:Exp Oncol;39(4):286-290, 2017 Dec.
[Is] ISSN:1812-9269
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:AIM: To study the status of the tumor growth factor beta (TGFB) pathway in chronic lymphocytic leukemia (CLL) cells and to uncover molecular details underlying CLL cell genesis. OBJECTS AND METHODS: The study was conducted on peripheral blood samples of patients with CLL using the following methods: RNA isolation, analysis of expression of transcription factors using RT2 profiler assay, bioinformatics analysis of publicly available data bases on expression. RESULTS: We have shown that the TGFB - SMAD canonical pathway is not active in CLL cells. SMAD-responsive genes, such as BCL2L1 (BCL-XL), CCND2 (Cyclin D2), and MYC, are down-regulated in CLL cells compared with peripheral blood B cells of healthy donors. CONCLUSIONS: The TGFB-mediated signaling is not active in CLL cells due to low (or absent) expression of SMAD1, -4, -5, -9, and ATF-3. Expression and phosphorylation status of SMAD2 and -3 should be further elucidated in the future studies.
[Mh] Termos MeSH primário: Leucemia Linfocítica Crônica de Células B/metabolismo
Proteínas Smad/metabolismo
Fator de Crescimento Transformador beta/metabolismo
[Mh] Termos MeSH secundário: Seres Humanos
Transdução de Sinais/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Smad Proteins); 0 (Transforming Growth Factor beta)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171230
[St] Status:MEDLINE


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Registro de Ensaios Clínicos
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[PMID]:29385370
[Au] Autor:Maude SL; Laetsch TW; Buechner J; Rives S; Boyer M; Bittencourt H; Bader P; Verneris MR; Stefanski HE; Myers GD; Qayed M; De Moerloose B; Hiramatsu H; Schlis K; Davis KL; Martin PL; Nemecek ER; Yanik GA; Peters C; Baruchel A; Boissel N; Mechinaud F; Balduzzi A; Krueger J; June CH; Levine BL; Wood P; Taran T; Leung M; Mueller KT; Zhang Y; Sen K; Lebwohl D; Pulsipher MA; Grupp SA
[Ad] Endereço:From the Departments of Pediatrics (S.L.M., S.A.G.) and Pathology and Laboratory Medicine (C.H.J., B.L.L.), Perelman School of Medicine, and Abramson Cancer Center (C.H.J., B.L.L.), University of Pennsylvania, and the Division of Oncology, Center for Childhood Cancer Research and Cancer Immunotherap
[Ti] Título:Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia.
[So] Source:N Engl J Med;378(5):439-448, 2018 02 01.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS: We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months. RESULTS: For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported. CONCLUSIONS: In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT02435849 .).
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Receptores de Antígenos de Linfócitos T/antagonistas & inibidores
Receptores de Antígenos de Linfócitos T/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Anticorpos Monoclonais Humanizados/administração & dosagem
Antígenos CD19
Criança
Pré-Escolar
Feminino
Seres Humanos
Infusões Intravenosas
Leucemia Linfocítica Crônica de Células B/mortalidade
Masculino
Indução de Remissão
Análise de Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal, Humanized); 0 (Antigens, CD19); 0 (CD19-specific chimeric antigen receptor); 0 (Receptors, Antigen, T-Cell); 0 (tisagenlecleucel); I031V2H011 (tocilizumab)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1709866


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[PMID]:29385200
[Au] Autor:Rout ED; Burnett RC; Labadie JD; Yoshimoto JA; Avery AC
[Ad] Endereço:Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
[Ti] Título:Preferential use of unmutated immunoglobulin heavy variable region genes in Boxer dogs with chronic lymphocytic leukemia.
[So] Source:PLoS One;13(1):e0191205, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, and immunoglobulin heavy variable region (IGHV) gene mutational status is an important prognostic marker. IGHV mutational status has not been previously examined in canine CLL. We sequenced the IGHV-D-J rearrangements from 55 canine patients with CLL, including 36 non-Boxer and 19 Boxer dogs. The majority of non-Boxers (75%) had mutated IGHV genes, whereas the majority of Boxers (79%) had unmutated IGHV genes. IGHV3-41 and IGHV3-67 gene usage was significantly higher in Boxers with CLL compared to non-Boxers. Additionally, 11 Boxers with large B-cell lymphoma and the normal IGHV repertoire of six control dogs (three Boxers and three non-Boxers) were sequenced. IGHV3-41 was preferentially used in Boxers with other forms of lymphoma and without lymphoproliferative disease. However, preferential use of unmutated IGHV genes was unique to Boxers with CLL, suggesting Boxers may be a valuable model to investigate unmutated CLL.
[Mh] Termos MeSH primário: Doenças do Cão/genética
Doenças do Cão/imunologia
Genes de Cadeia Pesada de Imunoglobulina
Região Variável de Imunoglobulina/genética
Leucemia Linfocítica Crônica de Células B/veterinária
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Estudos de Casos e Controles
Análise Mutacional de DNA
DNA de Neoplasias/genética
Cães
Feminino
Rearranjo Gênico de Cadeia Pesada de Linfócito B
Leucemia Linfocítica Crônica de Células B/genética
Leucemia Linfocítica Crônica de Células B/imunologia
Masculino
Mutação
Homologia de Sequência do Ácido Nucleico
Especificidade da Espécie
Éxons VDJ
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Neoplasm); 0 (Immunoglobulin Variable Region)
[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:180201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191205


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[PMID]:29193006
[Au] Autor:Rogers KA; Huang Y; Ruppert AS; Salem G; Stephens DM; Heerema NA; Andritsos LA; Awan FT; Byrd JC; Flynn JM; Maddocks KJ; Jones JA
[Ad] Endereço:Division of Hematology, The Ohio State University, Columbus, OH, USA.
[Ti] Título:A single-institution retrospective cohort study of first-line R-EPOCH chemoimmunotherapy for Richter syndrome demonstrating complex chronic lymphocytic leukaemia karyotype as an adverse prognostic factor.
[So] Source:Br J Haematol;180(2):259-266, 2018 01.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Richter Syndrome, an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia (CLL), has a generally poor prognosis and anthracycline-based chemoimmunotherapy regimens designed to treat de novo diffuse large B-cell lymphoma achieve modest clinical benefit. R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) has demonstrated greater activity against aggressive B-cell histologies but has not been studied in Richter Syndrome. We conducted a retrospective cohort study of 46 Richter Syndrome patients treated with first-line R-EPOCH at our institution between 1 January 2006 and 31 May 2014. The median progression-free survival (PFS) was 3·5 months [95% confidence interval (CI): 2·0-7·6] and median overall survival (OS) was 5·9 months (95% CI: 3·2-10·3). Toxicity was high and 30% of patients died without progression or response. Patients with a complex CLL karyotype had significantly shorter PFS and OS (P = 0·005 and P = 0·002, respectively). Multivariable analysis identified complex CLL karyotype as the most significant predictor of decreased survival [Hazard ratio (HR) 2·72, 95% CI: 1·14-6·52, P = 0·025], adjusting for number of prior CLL treatments (P = 0·036). Richter Syndrome patients with complex CLL karyotype experience poor survival with R-EPOCH treatment and novel approaches are needed for these patients. In contrast, survival of patients without a complex CLL karyotype was similar to patients with de novo diffuse large B-cell lymphoma.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Leucemia Linfocítica Crônica de Células B/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Biomarcadores Tumorais
Ciclofosfamida/efeitos adversos
Ciclofosfamida/uso terapêutico
Progressão da Doença
Doxorrubicina/efeitos adversos
Doxorrubicina/uso terapêutico
Etoposídeo/efeitos adversos
Etoposídeo/uso terapêutico
Feminino
Seres Humanos
Estimativa de Kaplan-Meier
Cariótipo
Leucemia Linfocítica Crônica de Células B/genética
Leucemia Linfocítica Crônica de Células B/mortalidade
Masculino
Meia-Idade
Prednisona/efeitos adversos
Prednisona/uso terapêutico
Prognóstico
Estudos Retrospectivos
Rituximab/administração & dosagem
Resultado do Tratamento
Vincristina/efeitos adversos
Vincristina/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 4F4X42SYQ6 (Rituximab); 5J49Q6B70F (Vincristine); 6PLQ3CP4P3 (Etoposide); 80168379AG (Doxorubicin); 8N3DW7272P (Cyclophosphamide); VB0R961HZT (Prednisone)
[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:171202
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.15035


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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]:29443669
[Au] Autor:El-Jawahri AR; Schaefer PW; El Khoury JB; Martinez-Lage M
[Ad] Endereço:From the Departments of Medicine (A.R.E.-J., J.B.E.K.), Radiology (P.W.S.), and Pathology (M.M.-L.), Massachusetts General Hospital, and the Departments of Medicine (A.R.E.-J., J.B.E.K.), Radiology (P.W.S.), and Pathology (M.M.-L.), Harvard Medical School - both in Boston.
[Ti] Título:Case 5-2018: A 63-Year-Old Man with Confusion after Stem-Cell Transplantation.
[So] Source:N Engl J Med;378(7):659-669, 2018 Feb 15.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Confusão/etiologia
Transplante de Células-Tronco Hematopoéticas/efeitos adversos
Herpesvirus Humano 6/isolamento & purificação
Hospedeiro Imunocomprometido
Meningoencefalite/diagnóstico
Infecções por Roseolovirus/diagnóstico
[Mh] Termos MeSH secundário: Antivirais/uso terapêutico
Autopsia
Diagnóstico Diferencial
Evolução Fatal
Foscarnet/uso terapêutico
Reação Enxerto-Hospedeiro
Seres Humanos
Leucemia Linfocítica Crônica de Células B/terapia
Masculino
Meningoencefalite/complicações
Meningoencefalite/virologia
Meia-Idade
Infecções por Roseolovirus/complicações
Infecções por Roseolovirus/tratamento farmacológico
Transplante Homólogo
[Pt] Tipo de publicação:CASE REPORTS; CLINICAL CONFERENCE; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 364P9RVW4X (Foscarnet)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMcpc1707556


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[PMID]:29390452
[Au] Autor:Liu G; Wen Z; Lu X; Kim YM; Wang X; Crew RM; Cherry MA; Li S; Liu Y
[Ad] Endereço:Department of Gastroenterology.
[Ti] Título:Coexistence of t(2;14;11)(p16.1;q32;q23) and t(14;19)(q32;q13.3) chromosome translocations in a patient with chronic lymphocytic leukemia: A case report.
[So] Source:Medicine (Baltimore);96(51):e9169, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: With combination of multiple techniques, we have successfully characterized unique, complex chromosomal changes in a patient with chronic lymphocytic leukemia (CLL), a lymphoproliferative disorder. DIAGNOSES: The diagnosis was based on white blood cell, flow cytometry, and immunophenotypes and confirmed by karyotype, fluorescence in situ hybridization, and array comparative genomic hybridization from the patient's blood culture. INTERVENTIONS: The patient was given fludarabine, cyclophosphamide and rituximab (FCR) for 6 cycles. OUTCOMES: After completion of 6 cycles of FCR, the computed tomography scans of the neck/chest/abdomen/pelvic showed that the patient in CR. During the 10-month follow-up, the patient's clinical course remained uneventful. LESSONS: The translocation t(14;19) identified in this patient is a recurrent translocation found in patients with chronic B-cell lymphoproliferative disorders and the 3-way translocation involving chromosomes 2, 14, and 11 may play a role as an enhancer.
[Mh] Termos MeSH primário: Cromossomos Humanos Par 11
Cromossomos Humanos Par 14
Cromossomos Humanos Par 2
Leucemia Linfocítica Crônica de Células B/genética
Translocação Genética
[Mh] Termos MeSH secundário: Adulto
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Ciclofosfamida/administração & dosagem
Feminino
Seres Humanos
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico
Rituximab/administração & dosagem
Vidarabina/administração & dosagem
Vidarabina/análogos & derivados
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
4F4X42SYQ6 (Rituximab); 8N3DW7272P (Cyclophosphamide); FA2DM6879K (Vidarabine); P2K93U8740 (fludarabine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009169



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