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1.
Ann Intern Med ; 167(6): 410-417, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-28828492

RESUMO

BACKGROUND: Screening for cancer in patients with unprovoked venous thromboembolism (VTE) often is considered, but clinicians need precise data on cancer prevalence, risk factors, and the effect of different types of screening strategies. PURPOSE: To estimate the prevalence of occult cancer in patients with unprovoked VTE, including in subgroups of different ages or those that have had different types of screening. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to 19 January 2016. STUDY SELECTION: Prospective studies evaluating cancer screening strategies in adults with unprovoked VTE that began enrolling patients after 1 January 2000 and had at least 12 months of follow-up. DATA EXTRACTION: 2 investigators independently reviewed abstracts and full-text articles and independently assessed risk of bias. DATA SYNTHESIS: 10 eligible studies were identified. Individual data were obtained for all 2316 patients. Mean age was 60 years; 58% of patients received extensive screening. The 12-month period prevalence of cancer after VTE diagnosis was 5.2% (95% CI, 4.1% to 6.5%). The point prevalence of cancer was higher in patients who had extensive screening than in those who had more limited screening initially (odds ratio [OR], 2.0 [CI, 1.2 to 3.4]) but not at 12 months (OR, 1.4 [CI, 0.89 to 2.1]). Cancer prevalence increased linearly with age and was 7-fold higher in patients aged 50 years or older than in younger patients (OR, 7.1 [CI, 3.1 to 16]). LIMITATION: Variation in patient characteristics and extensive screening strategies; unavailability of long-term mortality data. CONCLUSION: Occult cancer is detected in 1 in 20 patients within a year of receiving a diagnosis of unprovoked VTE. Older age is associated with a higher cancer prevalence. Although an extensive screening strategy initially may detect more cancer cases than limited screening, whether this translates into improved patient outcomes remains unclear. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42016033371).


Assuntos
Detecção Precoce de Câncer , Neoplasias/diagnóstico , Tromboembolia Venosa/complicações , Humanos , Estadiamento de Neoplasias , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/patologia , Prevalência , Fatores de Risco
2.
Haematologica ; 100(3): 392-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25527562

RESUMO

This study aimed to determine the impact of tyrosine kinase inhibitors given pre- and post-allogeneic stem cell transplantation on long-term outcome of patients allografted for Philadelphia chromosome-positive acute lymphoblastic leukemia. This retrospective analysis from the EBMT Acute Leukemia Working Party included 473 de novo Philadelphia chromosome-positive acute lymphoblastic leukemia patients in first complete remission who underwent an allogeneic stem cell transplantation using a human leukocyte antigen-identical sibling or human leukocyte antigen-matched unrelated donor between 2000 and 2010. Three hundred and ninety patients received tyrosine kinase inhibitors before transplant, 329 at induction and 274 at consolidation. Kaplan-Meier estimates of leukemia-free survival, overall survival, cumulative incidences of relapse incidence, and non-relapse mortality at five years were 38%, 46%, 36% and 26%, respectively. In multivariate analysis, tyrosine-kinase inhibitors given before allogeneic stem cell transplantation was associated with a better overall survival (HR=0.68; P=0.04) and was associated with lower relapse incidence (HR=0.5; P=0.01). In the post-transplant period, multivariate analysis identified prophylactic tyrosine-kinase inhibitor administration to be a significant factor for improved leukemia-free survival (HR=0.44; P=0.002) and overall survival (HR=0.42; P=0.004), and a lower relapse incidence (HR=0.40; P=0.01). Over the past decade, administration of tyrosine kinase inhibitors before allogeneic stem cell transplantation has significantly improved the long-term allogeneic stem cell transplantation outcome of adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Prospective studies will be of great interest to further confirm the potential benefit of the prophylactic use of tyrosine kinase inhibitors in the post-transplant setting.


Assuntos
Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Doadores não Relacionados
3.
Eur J Haematol ; 90(2): 162-3, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23227803

RESUMO

The prognosis of therapy refractory angioimmunoblastic lymphoma (AITL) is very poor. In this report we describe a patient with AITL refractory to 2 lines of chemotherapy. He was treated with lenalidomide 15 mg continuously and prednisone. After 2 yr follow-up, the patient has no detectable disease. Lenalidomide was well tolerated without side-effects. Lenalidomide even in lower dosed combined with steroids can induce complete responses in patients with refractory AITL.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Linfadenopatia Imunoblástica/tratamento farmacológico , Linfoma de Células T/tratamento farmacológico , Prednisona/administração & dosagem , Talidomida/análogos & derivados , Humanos , Linfadenopatia Imunoblástica/patologia , Lenalidomida , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Talidomida/administração & dosagem
4.
BMJ Open ; 7(6): e015562, 2017 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-28601834

RESUMO

INTRODUCTION: Occult cancer is present in 4%-9% of patients with unprovoked venous thromboembolism (VTE). Screening for cancer may be considered in these patients, with the aim to diagnose cancers in an early, potentially curable stage. Information is needed about the risk of occult cancer, overall and in specific subgroups, additional risk factors and on the performance of different screening strategies. METHODS AND ANALYSIS: MEDLINE, Embase and CENTRAL databases were searched from November 2007 to January 2016 for prospective studies that had evaluated protocol-mandated screening for cancer in patients with unprovoked VTE and with at least 12 months' follow-up. Two reviewers independently assessed articles for eligibility. Ten eligible studies were identified and individual patient data were obtained from each of them. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool . Generalised linear mixed-effects models was used to calculate estimates in a one-stage meta-analytic approach, overall and in a number of subgroups, including patients undergoing limited screening only, elderly patients, patients with previous VTE, smokers and patients using oestrogens. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review and individual patient data meta-analysis. Findings have been submitted for publication in peer-reviewed journals and presentations at national and international conferences to provide clinicians and other decision-makers with valid and precise risk estimates of occult cancer, overall and in specific clinical subgroups, with risk factors for occult cancer, with estimates of the diagnostic performance of limited screening and with an exploration of the benefit of extensive screening strategies.


Assuntos
Detecção Precoce de Câncer , Neoplasias/diagnóstico , Tromboembolia Venosa/etiologia , Detecção Precoce de Câncer/métodos , Humanos , Programas de Rastreamento/métodos , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Risco , Revisões Sistemáticas como Assunto
5.
Haematologica ; 90(2): 214-9, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15710574

RESUMO

BACKGROUND AND OBJECTIVES: Venous thromboembolism can be related to malignancy, but routine screening for cancer in patients with deep vein thrombosis (DVT) is not a recommended practice. The aim of this study was to evaluate the value of D-dimer concentration in predicting cancer in patients with DVT. DESIGN AND METHODS: D-dimer levels were measured in outpatients presenting with DVT. In a proportion of patients, D-dimer levels were measured daily for 4 days. The occurrence of malignancy was documented. RESULTS: Patients were followed for a median of 34 months. Fifty (23%) of 218 patients with thrombosis had cancer in the study period including 14 who developed cancer during the follow-up. High initial D-dimer levels (levels > 4000 mg/L) were associated with more cancer during follow-up than were lower D-dimer levels: 13% versus 4% (p=0.048). High D-dimer levels after 4 days of treatment were associated with a 15% prevalence of cancer whereas the prevalence in patients with lower D-dimer levels was 5% (p=0.1). The total cancer prevalence (including cancer diagnosed before thrombosis) in patients with initial D-dimer levels < 4000 mg/L was 16% compared to 32% in patients with higher levels (p=0.009, RR=2.0). After 4 days of treatment, total cancer prevalences were 14% and 46%, respectively (p=0.02, RR=3.4). In patients aged < 60 years, initial D-dimer levels of < 4000 mg/L were associated with a cancer prevalence of 3% whereas higher levels were associated with a prevalence of 23% (p=0.001, RR=8.6). After 4 days of treatment, the prevalences associated with lower and higher levels of D-dimer were 0% and 100%, respectively (p=0.003). There was no difference in older patients. INTERPRETATION AND CONCLUSIONS: High D-dimer concentrations at presentation or during the first days of treatment are indicators of an increased probability of overt or occult forms of cancer, especially in patients under 60 years old.


Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/biossíntese , Neoplasias/sangue , Neoplasias/complicações , Trombose Venosa/sangue , Trombose Venosa/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Valor Preditivo dos Testes , Prevalência , Trombose Venosa/diagnóstico
6.
Leuk Res ; 38(1): 34-41, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24238639

RESUMO

Resistance to chemotherapy-induced apoptosis in CLL is associated with overexpression of antiapoptotic proteins induced by signals from the microenvironment. In vitro, dasatinib effectively inhibits expression of anti-apoptotic regulators and restores fludarabine sensitivity in activated CLL. The aim of this study was to evaluate efficacy of one cycle of dasatinib monotherapy (100mg/day, days 1-28) followed by combination of dasatinib with fludarabine (40mg/m²/day, days 1-3 every 28 day) for a total of 6 cycles in fludarabine-refractory CLL. The primary endpoint was overall response rate according to the IWCLL'08 criteria. 20 patients were enrolled: 18 completed at least one cycle of treatment of which 67% finished at least 2 cycles of combination treatment. 3 of these 18 patients reached a formal PR (16.7%). Majority of patients obtained some reduction in lymph node (LN) size. Most frequent toxicity was related to myelosuppression. NF-κB RNA expression levels of circulating CLL cells decreased whereas the levels of pro-apoptotic NOXA increased during treatment. In conclusion, dasatinib/fludarabine combination has modest clinical efficacy in fludarabine-refractory patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Pirimidinas/uso terapêutico , Tiazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Dasatinibe , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , Náusea/induzido quimicamente , Pneumonia/induzido quimicamente , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados
7.
Ned Tijdschr Geneeskd ; 154: A2025, 2010.
Artigo em Holandês | MEDLINE | ID: mdl-20977803

RESUMO

OBJECTIVE: To describe activities in the field of autologous stem cell transplantation in haematological disorders in the Netherlands in the periods before and after 1993 (at that time blood was introduced as source of stem cells). DESIGN: Descriptive, retrospective cohort study. METHOD: Data were collected from the Netherlands Stem Cell Transplantation Registry TYPHON. Details of all transplant patients were reported to TYPHON by the individual transplantation centres. In this overview we describe the changes in transplantation-related mortality, relapse rates and survival in the periods 1 January 1980-31 December 1992 and 1 January 1980-31 December 2002. RESULTS: The number of autologous stem cell transplantations increased almost five-fold in the period 1993-2002. Since 1993 the main indications for transplantation were multiple myeloma (MM) and non-Hodgkin lymphoma (NHL), as well as acute myeloid leukaemia (AML), which was the main indication in the period before 1993. In the period before 1993 most relapses were observed in patients with acute lymphoblastic leukaemia (ALL) and MM, which resulted in low survival rates. After 1993 no great differences in relapse or survival rates were observed between the different disorders. The survival rates for patients with ALL improved during the last research period, especially among younger patients (< 45 years). CONCLUSION: The number of autologous stem cell transplantations has increased considerably since 1993, especially in patients with MM and NHL.


Assuntos
Doenças Hematológicas/mortalidade , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo , Adulto Jovem
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