Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
1.
Ann Hematol ; 101(1): 81-89, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34550463

RESUMO

Ixazomib is approved for use in combination with lenalidomide and dexamethasone (IRd) for patients with multiple myeloma (MM) who received at least one previous therapy. Registration study "TOURMALINE MM-1" was published in 2016. Nevertheless, clinical trials are significantly different from real-world use. From June 2016 to December 2018, IRd was available for Slovak patients with relapsed/refractory MM through a Named Patient Program. The aim of this study was to evaluate the efficacy and safety of ixazomib. We analyzed in this cohort study outcomes of 106 MM patients treated with IRd at 2 academic centers. The median age at diagnosis was 63 years (44-78). The median number of prior lines was 2 (1-7). The majority had high international staging system (ISS) score: 18, 29, and 59 were in the ISS I, ISS II, and ISS III groups, respectively. Treatment continued until progression, unacceptable toxicity, or death. The median follow-up for the entire cohort was 29 (0-49) months. The overall response rate was 74.5% (complete remission, 7.5%; partial remission, 67%). The median overall survival was not reached. Median progression-free survival (PFS) was 43 months (95% CI 35.6-50.4). The Kaplan-Meier method was used to generate survival curves, and we compared the influence of different factors on PFS. The most common hematological adverse events of any grade were neutropenia (90.4%), anemia (55.6%), and thrombocytopenia (43.4%). Our real-world data support the use of IRd as a highly effective and well-tolerated oral treatment protocol for relapsed myeloma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos de Boro/uso terapêutico , Dexametasona/uso terapêutico , Glicina/análogos & derivados , Lenalidomida/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos de Boro/efeitos adversos , Estudos de Coortes , Dexametasona/efeitos adversos , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Lenalidomida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/epidemiologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/epidemiologia , Neutropenia/induzido quimicamente , Eslováquia/epidemiologia
2.
Neoplasma ; 68(3): 626-630, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33567854

RESUMO

Real-world data on regimens for relapsed/refractory multiple myeloma (RRMM) are limited. Daratumumab in combination with bortezomib and dexamethasone is a promising new treatment. The aim of this analysis was to assess the outcomes of daratumumab-bortezomib-dexamethasone (DVd) combination for the treatment of patients with RRMM in a real-world setting. All consecutive RRMM patients who received at least two cycles of DVd treatment between December 2016 and July 2020 were identified. We analyzed the clinical characteristics and survival of 47 patients treated at 7 Slovak centers outside of the clinical trials. The median age was 65 years (range, 35 to 83). The median (range) number of lines of therapy per patient was 3 (2-6). All patients were previously exposed to PIs (proteasome inhibitors) and IMIDs (immunomodulatory drugs), the majority of patients (70.2%) had double refractory (IMIDs and PI) disease and 72.3% of patients were refractory to their last therapy. Most patients presented with high-risk characteristics, including 25.6% adverse cytogenetics and 25.5% extramedullary disease. The majority of patients responded with an overall response rate of 78%, we found complete response in 3, very good partial response in 22, partial response in 12, minor response or stable disease in 9, and progressive disease in 1 patient. After a median follow-up period of 8 months, the median progression-free survival was 10 months. There was a longer progression-free survival in those with 2 vs. >2 prior treatments, with equally good effectivity in standard-risk and high-risk cytogenetic groups. The adverse events were usually mild, none leading to permanent drug interruptions. Daratumumab-bortezomib-based combinations are efficacious and safe regimens in RRMM patients in the real-world setting. This is the first analysis in Slovakia addressing the DVd combination outside of the clinical trial setting.


Assuntos
Mieloma Múltiplo , Idoso , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Humanos , Mieloma Múltiplo/tratamento farmacológico , Eslováquia
3.
Vnitr Lek ; 66(8): 39-46, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33740859

RESUMO

Heparin-induced thrombocytopenia (HIT) is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to low-molecular weight heparin. Some patients with HIT develop serious thrombotic complications like limb ischemia and gangrene, while others may not develop such complications. Current laboratory diagnostic tools incur significant time delays before confirming HIT, therefore upon clinical suspicion, treatment of HIT should start immediately. In this review, the authors highlight heparin-induced thrombocytopenias risk factors, clinical presentation, pathophysiology, diagnostic principles, and treatment.


Assuntos
Trombocitopenia , Trombose , Anticoagulantes/efeitos adversos , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Trombocitopenia/induzido quimicamente
4.
Vnitr Lek ; 62(4): 281-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27250605

RESUMO

INTRODUCTION: Factor V Leiden (FVL) and prothrombin G20210A mutation (PTM) are the two most common genetic polymorphisms known to predispose to a first episode of venous thromboembolism (VTE). PTM is present in 2 % Caucasian population. The main aim of this study was to identify the PTM in the patients with positive history of thrombotic events vs. control subjects. MATERIALS AND METHODS: The assessment of PTM was performed by the PCR analysis of the chromosomal DNA, which was isolated from the peripheral blood leukocytes. RESULTS: Of the 2 274 patients included, 157 (6.9 %) were carriers of the PTM. The mutation was present only in 2.6 % (n = 8) of the 303 controls. The following clinical manifestations of PTM were analysed. We observed 123 venous thrombotic events, 46 arterial thrombosis and 14 spontaneous abortions. In this article we analyse other possible risk factors for thromboembolic events in patients with carriage of PTM. CONCLUSIONS: To our knowledge, this is the largest epidemiological study of PTM in Central Europe. Employing statistical analysis, we found relatively high prevalence of the PTM in both, the patients with positive thrombosis history (6.9 %), as well as in the control group (2.6 %). The risk of thrombosis by carriage of PTM is independent of age and gender. Study has shown relatively frequent presence of double carriership of PTM and factor V Leiden mutation (FVL).


Assuntos
Heterozigoto , Mutação , Protrombina/genética , Aborto Espontâneo/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Gravidez , Eslováquia , Trombose/epidemiologia , Adulto Jovem
5.
Gen Physiol Biophys ; 34(1): 33-42, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25367763

RESUMO

Bortezomib (PS-341, or Velcade), reversible inhibitor of 20S proteasome approved for the treatment of multiple myeloma and mantle cell lymphoma, exhibited a cytotoxic effect toward other malignancies including leukaemia. In this study, we have documented that incubation of both HL-60 and K562 leukaemia cells with nanomolar concentrations of bortezomib is associated with the death of HL-60 cells observed within 24 hours of incubation with bortezomib and the death of K562 cells that were observed after 72 hours of incubation with bortezomib. The relative resistance of K562 cells to bortezomib correlated well with significantly higher expression of HSP27, HSP70, HSP90α, HSP90ß and GRP75 in these cells. Incubation of both HL-60 and K562 cells with bortezomib induced a cleavage of HSP90ß as well as expression of HSP70 and HSP90ß but bortezomib did not affect levels of HSP27, HSP90α, GRP75 and GRP78. The death of both types of cells was accompanied with proteolytic activation of caspase 3 that was observed in HL-60 cells and proteolytic degradation of procaspase 3 in K562 cells. Our study has also pointed to essential role of caspase 8 in bortezomib-induced cleavage of HSP90ß in both HL-60 and K562 cells. Finally, we have shown that bortezomib induced activation of caspase 9/caspase 3 axis in HL-60 cells, while the mechanism of death of K562 cells remains unknown.


Assuntos
Antineoplásicos/farmacologia , Ácidos Borônicos/farmacologia , Regulação Leucêmica da Expressão Gênica , Leucemia/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Pirazinas/farmacologia , Apoptose , Bortezomib , Morte Celular , Sobrevivência Celular , Relação Dose-Resposta a Droga , Chaperona BiP do Retículo Endoplasmático , Células HL-60/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Células K562/efeitos dos fármacos , Fatores de Tempo
6.
Am J Hematol ; 88(9): 790-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23760739

RESUMO

Using the data of 723 chronic myeloid leukemia (CML) patients in the chronic phase, we analyzed the prognostic value of the Sokal, Euro, and EUTOS scores as well as the level of BCR-ABL1 and the achievement of complete cytogenetic response (CCgR) at 3 months of imatinib therapy in relation to the so-called current survival measures: the current cumulative incidence (CCI) reflecting the probability of being alive and in CCgR after starting imatinib therapy; the current leukemia-free survival (CLFS) reflecting the probability of being alive and in CCgR after achieving the first CCgR; and the overall survival. The greatest difference between the CCI curves at 5 years after initiating imatinib therapy was observed for the BCR-ABL1 transcripts at 3 months. The 5-year CCI was 94.3% in patients with BCR-ABL1 transcripts ≤ 10% and 57.1% in patients with BCR-ABL1 transcripts > 10% (P = 0.005). Therefore, the examination of BCR-ABL1 transcripts at 3 months may help in early identification of patients who are likely to perform poorly with imatinib. On the other hand, CLFS was not significantly affected by the considered stratifications. In conclusion, our results indicate that once the CCgR is achieved, the prognosis is good irrespective of the starting prognostic risks.


Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Leucemia Mieloide de Fase Crônica/genética , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , RNA Mensageiro/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Mesilato de Imatinib , Leucemia Mieloide de Fase Crônica/diagnóstico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , RNA Mensageiro/metabolismo , Indução de Remissão , Projetos de Pesquisa , Análise de Sobrevida , Resultado do Tratamento
7.
Eur J Haematol ; 87(2): 157-68, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21535160

RESUMO

BACKGROUND: Most results on the treatment of chronic myeloid leukaemia (CML) with imatinib were obtained from clinical trials that may differ from the routine practice. We report the results of treatment of consecutive patients with CML at ten major centres during 2000-2008. PATIENTS AND METHODS: Data reporting was retrospective in 2000-2004 and prospective from 2005 on. A total of 661 patients [301 women and 360 men; median age 51 (range, 15-83)] with Ph+CML were registered. The median follow-up was 46.1 months (0-122.2). RESULTS: Most patients were treated with first- (379; 57.3%) or second-line (193; 29.2%) imatinib; some of the patients underwent allogeneic hematopoietic stem cell transplantation (AHSCT) (83; 12.6%), but 6.1% were treated with other modalities [40 patients; median age 66 (range, 32-83)]. The probability of overall survival (OS) at 5 years, according to Kaplan and Meier, was 88.9%, 77.5% and 68.7% for chronic-phase patients treated with first-line imatinib, second-line imatinib and first-line AHSCT, respectively, but only 25.2% for patients receiving other modalities. The OS was dependent on the disease phase and Sokal, Hasford and European group for blood and marrow transplantation (EBMT) risk scores (P<0.001; each). Only 46.2% of deaths in patients treated with other modalities were attributable to CML. Elderly patients over 65 years achieved similar response rates and progression-free survival to the younger ones. There was a trend for inferior results of AHSCT performed after the failure of imatinib (P=0.075), probably as a result of differences in EBMT risk scores (P<0.001). CONCLUSIONS: The ability to achieve results comparable to those of previous clinical studies in our CML cohort was influenced by centralised care. Decisions not to initiate imatinib or to delay AHSCT may have a negative impact on OS, but comorbidities may limit the treatment potential of imatinib in the elderly.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Benzamidas , República Tcheca/epidemiologia , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Mesilato de Imatinib , Estimativa de Kaplan-Meier , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Estudos Prospectivos , Pirimidinas/uso terapêutico , Sistema de Registros , Estudos Retrospectivos , Eslováquia/epidemiologia , Transplante Homólogo , Adulto Jovem
8.
Int J Mol Med ; 22(6): 833-9, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19020783

RESUMO

Tumour suppressor protein p53 prevents cancer development through various mechanisms, including the induction of apoptosis. We demonstrated that acute leukaemia, myeloblastic (AML) and lymphoblastic (ALL), is associated with significantly elevated levels of p53 and Bax mRNA in leukaemic cells. Regarding ALL, significantly elevated levels of Bcl-xL mRNA may explain the relative resistance of ALL cells to p53-dependent apoptosis. Altered alternative processing of Bcl-x and myeloid cell leukaemia-1 (MCL1) primary transcripts were observed in the case of AML and AML and ALL, respectively. We assumed that increased glyceraldehyde-3-phosphate dehydrogenase (gapdh) transcription and decreased MCL1s mRNA were not fully responsible for the dysregulation of p53-dependent apoptosis in the case of AML. In addition, transcription of hsp70.1 and Bcl-2 producing anti-apoptotic proteins was not affected in acute leukaemia.


Assuntos
Apoptose , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Transcrição Gênica , Proteína Supressora de Tumor p53/genética , Actinas/genética , Actinas/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/genética , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Leucócitos Mononucleares/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides , Polimorfismo Conformacional de Fita Simples , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismo
9.
Int J Surg Case Rep ; 13: 84-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26150051

RESUMO

INTRODUCTION: Superior vena cava syndrome (SVCS) is obstruction of blood flow through the SVC. It is a medical emergency and most often manifests in patients with a malignant disease process within the thorax. A patient with SVCS requires immediate diagnostic evaluation and therapy. PRESENTATION OF CASE: A 33-years-old woman presented with complaints of dyspnoea and chest pain. Computer tomography revealed a large mass in the anterior mediastinum. This mass compressed surrounding structures. Stenting was indicated for early symptoms of SVCS. The diagnosis of Hodgkin's lymphoma (HL) was confirmed with biopsy. The patient's stage II HL has been subsequently treated with six cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD), followed by radiotherapy. Presently she is doing well. DISCUSSION: Although lymphomas are a common cause of SVCS but almost always SVCS is caused by non-Hodgkin's lymphoma (NHL). HL despite its common presentation with mediastinal lymphadenopathy rarely causes SVCS. CONCLUSION: Lymphomas are a common cause of SVCS in young age. HL may present as SVCS. Pathological confirmation of diagnosis should be done before initiating therapy while dealing with a case of SVCS. SVC stenting is effective and has few complications in patients with SVCS.

11.
Cancer Med ; 2(2): 216-25, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23634289

RESUMO

We evaluated responses to the treatment and long-term outcomes of chronic myeloid leukemia patients treated with imatinib as first-line treatment in routine clinical setting from two countries with centralized tyrosine kinase inhibitors (TKIs) treatment. We assessed prognostic significance of European LeukemiaNet (ELN) 2006- and 2009-defined responses and the prognostic value of molecular responses at defined time points on 5-year survivals. Among the cumulative rates of incidence of hematologic, cytogenetic, and molecular responses and all important survival parameters, we evaluated the prognostic significance of different BCR-ABL transcript-level ratios (≤1%; >1%-≤10%; >10%) at 3, 6, 12, and 18 months (n = 199). The ELN optimal response criteria and their predictive role were significantly beneficial for event-free survival at all given time points. We found significant improvement in survivals of patients with BCR-ABL lower than 10% in the 6th and 12th months. Significantly better outcome was found in patients who achieved major molecular response (MMR) in the 12th month. The cumulative incidences of complete cytogenetic response (CCyR) and MMR were significantly associated with the molecular response in the 3rd month. The ELN response criteria and their predictive role were helpful at given time points; however, the 2009 definition did not significantly alter the prognostic accuracy compared with that of the 2006 definition. The significant value was observed for cytogenetic responses at the 6th and 12th month. Moreover, progression-free and event-free survivals were improved with MMR at the 12th month.


Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa