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1.
Br J Haematol ; 184(5): 753-759, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30515755

RESUMO

Follicular lymphoma (FL) is an indolent disease characterized by long survival but frequent relapses. Before the introduction of rituximab, the clinical course of these patients showed a shorter response duration (RD) after each relapse. In this study, we analysed if this pattern of shortened responses remains in patients treated in the rituximab era. We selected 348 patients newly diagnosed with FL in two institutions between 2001 and 2014 that received chemoimmunotherapy. After a median follow-up of 6·3 years, 10-year progression-free and overall survivals were 53% and 72%, respectively. All patients received first-line, 111 second-line and 41 third-line treatments, with a 5-year RD of 62%, 39% and 24%, respectively (P < 0·0001). Variables predicting longer RD after first-line treatment were normal ß2microglobulin, complete remission achievement and maintenance with rituximab. Patients with longer RD after first-line showed significantly longer RD after second-line therapy. Autologous stem-cell transplantation after second-line therapy did not significantly impact RD. Median survival after first, second and third therapies was not reached, 7·6 and 4·8 years, respectively, whereas relative survival with respect to a sex- and age-matched Spanish population, the decrease in the life expectancy at 10 years was 17%, 45% and 79%, respectively. Thus, RD still shortens after each relapse in patients with FL treated in first line with rituximab combinations.


Assuntos
Linfoma Folicular , Quimioterapia de Manutenção , Rituximab/administração & dosagem , Transplante de Células-Tronco , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Recidiva , Espanha , Taxa de Sobrevida
4.
Am J Hematol ; 92(4): 375-380, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28120419

RESUMO

Rai and Binet staging systems are important to predict the outcome of patients with chronic lymphocytic leukemia (CLL) but do not reflect the biologic diversity of the disease nor predict response to therapy, which ultimately shape patients' outcome. We devised a biomarkers-only CLL prognostic system based on the two most important prognostic parameters in CLL (i.e., IGHV mutational status and fluorescence in situ hybridization [FISH] cytogenetics), separating three different risk groups: (1) low-risk (mutated IGHV + no adverse FISH cytogenetics [del(17p), del(11q)]); (2) intermediate-risk (either unmutated IGHV or adverse FISH cytogenetics) and (3) high-risk (unmutated IGHV + adverse FISH cytogenetics). In 524 unselected subjects with CLL, the 10-year overall survival was 82% (95% CI 76%-88%), 52% (45%-62%), and 27% (17%-42%) for the low-, intermediate-, and high-risk groups, respectively. Patients with low-risk comprised around 50% of the series and had a life expectancy comparable to the general population. The prognostic model was fully validated in two independent cohorts, including 417 patients representative of general CLL population and 337 patients with Binet stage A CLL. The model had a similar discriminatory value as the CLL-IPI. Moreover, it applied to all patients with CLL independently of age, and separated patients with different risk within Rai or Binet clinical stages. The biomarkers-only CLL prognostic system presented here simplifies the CLL-IPI and could be useful in daily practice and to stratify patients in clinical trials.


Assuntos
Leucemia Linfocítica Crônica de Células B/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Estudos de Coortes , Genes de Cadeia Pesada de Imunoglobulina , Humanos , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/mortalidade , Pessoa de Meia-Idade , Mutação , Prognóstico , Medição de Risco , Taxa de Sobrevida , Adulto Jovem
5.
Ther Adv Hematol ; 7(6): 321-329, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27904736

RESUMO

B-cell lymphoma 2 (BCL2)-type proteins are key regulators of the intrinsic or mitochondrial pathway for apoptosis. Since escape from apoptosis is one the main 'hallmarks of cancer', BCL2 inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). Multiple clinical trials have shown efficacy of these agents in patients with relapsed/refractory disease with a favorable toxicity profile. Moreover, some clinical trials indicate that combination with monoclonal antibodies and other novel agents may enhance their effect.

6.
Med Clin (Barc) ; 147(10): 447-454, 2016 Nov 18.
Artigo em Espanhol | MEDLINE | ID: mdl-27431885

RESUMO

Chronic lymphocytic leukemia (CLL), a proliferation of mature B cells, is one of the most prevalent haematological malignancies. Progress has been made in its treatment during the last few decades, and chemoimmunotherapy based on fludarabine, cyclophosphamide and rituximab is considered the treatment of choice for patients with standard-risk CLL and good performance status. However, due to the characterization of high-risk biological subgroups and its presentation in elderly patients and/or with comorbidities, targeted therapies, such as B-cell receptor inhibitors, have been developed and approved during the last few years. The current review examines traditional therapeutic strategies and focuses on new small molecules that already represent promising elements of the CLL treatment landscape.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores Imunológicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/terapia
7.
Med. clín (Ed. impr.) ; 147(10): 447-454, nov. 2016. tab, ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-157776

RESUMO

La leucemia linfocítica crónica (LLC) es una proliferación de linfocitos B maduros que constituye una de las neoplasias hematológicas más prevalentes. Su tratamiento ha evolucionado en las últimas décadas hasta considerarse la inmunoquimioterapia a base de fludarabina, ciclofosfamida y rituximab el tratamiento de elección en pacientes de riesgo estándar y con buena situación funcional. Sin embargo, la caracterización de subgrupos biológicos de alto riesgo y la presentación de esta enfermedad en pacientes de edad avanzada y/o con comorbilidad ha llevado en los últimos años al desarrollo y aprobación de tratamientos dirigidos, especialmente los inhibidores del receptor del linfocito B. La presente revisión repasa las estrategias terapéuticas convencionales y se centra en las nuevas moléculas que ya constituyen elementos prometedores del actual panorama terapéutico de la LLC (AU)


Chronic lymphocytic leukemia (CLL), a proliferation of mature B cells, is one of the most prevalent haematological malignancies. Progress has been made in its treatment during the last few decades, and chemoimmunotherapy based on fludarabine, cyclophosphamide and rituximab is considered the treatment of choice for patients with standard-risk CLL and good performance status. However, due to the characterization of high-risk biological subgroups and its presentation in elderly patients and/or with comorbidities, targeted therapies, such as B-cell receptor inhibitors, have been developed and approved during the last few years. The current review examines traditional therapeutic strategies and focuses on new small molecules that already represent promising elements of the CLL treatment landscape (AU)


Assuntos
Humanos , Masculino , Feminino , Leucemia Linfocítica Crônica de Células B/terapia , Receptores de Antígenos de Linfócitos B/análise , Imunoterapia/métodos , Imunoterapia , Ciclofosfamida/uso terapêutico , Rituximab/uso terapêutico , Alquilantes/uso terapêutico , Leucemia Linfocítica Crônica de Células B/epidemiologia , Leucemia Linfocítica Crônica de Células B/prevenção & controle , Comorbidade , Autoimunidade/fisiologia
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