Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 99
Filtrar
1.
Ann Oncol ; 26(6): 1118-1123, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25701452

RESUMO

BACKGROUND: We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). PATIENTS AND METHODS: A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. RESULTS: We recruited 55 eligible participants from September 2010 to August 2012. DEMOGRAPHICS: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5-10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12-undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. CONCLUSIONS: The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12609000643279.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Everolimo/administração & dosagem , Indóis/administração & dosagem , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirróis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Austrália , Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Everolimo/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Indóis/efeitos adversos , Neoplasias Renais/enzimologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/efeitos adversos , Pirróis/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fatores de Risco , Sunitinibe , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo , Resultado do Tratamento
2.
Intern Med J ; 44(10): 939-50, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25039334

RESUMO

Improvements in survival from cancer have led to a large population who are at risk of late complications of chemotherapy. One of the most serious cardiovascular complications is chemotherapy-related cardiomyopathy (CRC), which may become clinically overt years or even decades after treatment and has over threefold higher mortality rate compared with idiopathic dilated cardiomyopathy. The early stages of this condition appear to respond well to cardioprotective medications (i.e. angiotensin-converting enzyme inhibitors, ß-blockers). Periodic cardiac monitoring is necessary in this population to identify patients who would benefit from treatment. Cardio-oncology clinics have been established in recognition of this hazard in survivorship. This review summarises the epidemiology and pathophysiology of CRC, the evidence base for different non-invasive imaging modalities for screening and diagnosis and the rationale for treatment.


Assuntos
Antineoplásicos/efeitos adversos , Cardiomiopatia Dilatada/induzido quimicamente , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/induzido quimicamente , Neoplasias/tratamento farmacológico , Sobreviventes , Cardiomiopatia Dilatada/diagnóstico , Medicina Baseada em Evidências , Insuficiência Cardíaca/prevenção & controle , Humanos , Seleção de Pacientes , Fatores de Risco , Fatores de Tempo
3.
Intern Med J ; 44(9): 897-902, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24861147

RESUMO

BACKGROUND: High-dose chemotherapy and autologous haematopoietic stem cell transplantation is an important therapeutic modality in the treatment of many haematological malignancies. Generally, stem cells are collected close to the time of the transplant, but an alternative is to collect and cryopreserve cells at an early stage of the illness so they are available for later use ('rainy day harvesting'). Although this practice has been commonplace in Australia, there is little evidence to document eventual use of cells collected in this manner. METHODS: We conducted an audit of indications for and eventual transplantation of 'rainy day' harvests performed at our institution over a 10-year period. RESULTS: Although there was some variation across different disease groups, we found that only 14% of cells were transplanted. The median delay to transplantation was 19 months. CONCLUSION: Together with recent advances in stem cell mobilisation techniques, results from this audit suggest that the practice may not be an effective use of limited health resources.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Coleta de Tecidos e Órgãos , Austrália/epidemiologia , Auditoria Clínica , Criopreservação , Feminino , Neoplasias Hematológicas/epidemiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Coleta de Tecidos e Órgãos/métodos , Coleta de Tecidos e Órgãos/normas , Transplante Autólogo
4.
Transfus Apher Sci ; 49(2): 110-2, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23962397

RESUMO

The Australasian Leukaemia and Lymphoma Group (ALLG) can trace its origins to 1973. It now encompasses virtually all the major hospitals in Australia and New Zealand that treat leukaemias and lymphomas. Over the years the Group as a whole, and members individually, have participated in many clinical treatment trials for aggressive lymphomas. Initially trials were conceived and carried out locally, but in recent years, in addition to continuing its own studies, the Group has been a major contributor to international trials including two that have been particularly influential, known as MInT and CORAL. The MInT study confirmed the value of adding rituximab to standard chemotherapy for aggressive lymphomas; CORAL helped define optimum methods of autografting for relapse. The ALLG has contributed and continues to contribute to the improving outcome for patients with aggressive lymphomas.


Assuntos
Leucemia/terapia , Linfoma/terapia , Austrália , Ensaios Clínicos como Assunto , Leucemia/diagnóstico , Linfoma/diagnóstico , Estudos Multicêntricos como Assunto , Nova Zelândia
5.
Intern Med J ; 42(2): 212-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22188466

RESUMO

Over the past 33 years, mystery has surrounded the diagnosis and treatment of a very influential Australian patient. In the long gap between amputation of his leg for osteogenic sarcoma and successful treatment for widespread tuberculosis, he was told he had advanced and incurable metastatic sarcoma. Details of his recovery and the treatments used have been extensively described. An alternative hypothesis is advanced to explain his recovery. This hypothesis is advanced for two reasons. The first is to underline the modern recognition of the need to consider diagnostic investigations, including biopsy, before assigning the diagnosis of advanced cancer to any patient. This principle is especially vital in cases where two diseases can present in the same way. The second is that there a risk that if diseases are incorrectly labelled, incorrect treatments may be given. This can lead to misleading interpretations being made about non-traditional treatments providing 'cures', which can influence the decision-making of patients seeking answers and even lead them away from potentially curative traditional treatments.


Assuntos
Osteossarcoma/diagnóstico , Osteossarcoma/terapia , Tuberculose/diagnóstico , Tuberculose/terapia , Humanos , Osteossarcoma/complicações , Indução de Remissão , Tuberculose/complicações
6.
Ann Oncol ; 22(8): 1834-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21273347

RESUMO

BACKGROUND: Bevacizumab is an antiangiogenic mAb with efficacy against several cancers, but it is associated with risk of arterial thromboembolism (ATE). Further data are needed to determine the safety of bevacizumab. PATIENTS AND METHODS: We recorded grade 3, 4, or 5 ATE events and other data (including age, baseline cardiovascular risk factors, history of ATE, and aspirin use) from 471 patients with metastatic colorectal cancer in the MAX (Mitomycin, Avastin, Xeloda) trial of capecitabine monotherapy versus capecitabine with bevacizumab with or without mitomycin C. RESULTS: Bevacizumab-treated patients had 12 grade 3, 4, or 5 ATEs (3.8% incidence). ATEs occurred in 2.1% of patients >65 years, 5% of those with a history of ATE, and 5% of those with cardiac risk factors. Age, history of ATE, or vascular risk factors did not increase risk. Aspirin users had a higher incidence than nonusers (8.9% versus 2.7%) but had higher rates of vascular risk factors. CONCLUSIONS: Bevacizumab was associated with a modestly higher risk of ATE, but safety was not significantly worse in older patients or patients with a history of ATE or vascular risk factors. The effect of aspirin in preventing ATE in patients receiving bevacizumab could not be determined from this study.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Tromboembolia/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Aspirina/uso terapêutico , Bevacizumab , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Risco
7.
Br J Cancer ; 103(7): 1128-35, 2010 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-20877339

RESUMO

BACKGROUND: Previous pooled analyses have reported an association between magnetic fields and childhood leukaemia. We present a pooled analysis based on primary data from studies on residential magnetic fields and childhood leukaemia published after 2000. METHODS: Seven studies with a total of 10,865 cases and 12,853 controls were included. The main analysis focused on 24-h magnetic field measurements or calculated fields in residences. RESULTS: In the combined results, risk increased with increase in exposure, but the estimates were imprecise. The odds ratios for exposure categories of 0.1-0.2 µT, 0.2-0.3 µT and ≥0.3 µT, compared with <0.1 µT, were 1.07 (95% CI 0.81-1.41), 1.16 (0.69-1.93) and 1.44 (0.88-2.36), respectively. Without the most influential study from Brazil, the odds ratios increased somewhat. An increasing trend was also suggested by a nonparametric analysis conducted using a generalised additive model. CONCLUSIONS: Our results are in line with previous pooled analyses showing an association between magnetic fields and childhood leukaemia. Overall, the association is weaker in the most recently conducted studies, but these studies are small and lack methodological improvements needed to resolve the apparent association. We conclude that recent studies on magnetic fields and childhood leukaemia do not alter the previous assessment that magnetic fields are possibly carcinogenic.


Assuntos
Campos Eletromagnéticos/efeitos adversos , Leucemia Induzida por Radiação/epidemiologia , Criança , Pré-Escolar , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , Risco
8.
Intern Med J ; 37(9): 614-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17543004

RESUMO

BACKGROUND: Studies have shown an association between electromagnetic fields and childhood leukaemia. The aim of this study was to determine whether there is an increased risk of lymphoproliferative disorders (LPD) or myeloproliferative disorders (MPD) associated with residence < or =300 m from high-voltage power lines. METHODS: Case-control study of 854 patients diagnosed with LPD or MPD (including leukaemia, lymphoma and related conditions) aged 0-94 years comprising all cases diagnosed in Tasmania between 1972 and 1980. Controls were individually matched for sex and approximate age at the time of diagnosis. RESULTS: Compared with those who had always lived >300 m from a power line, those who had ever lived within 50 m had an odds ratio (OR) of 2.06 (95% confidence interval 0.87-4.91) for developing LPD or MPD (based on 768 adult case-control pairs); those who had lived between 50 and 300 m had an OR of 1.30 (0.88-1.91). Adults who had lived within 300 m of a power line during the first 15 years of life had a threefold increase in risk (OR 3.23; 1.26-8.29); those who had lived within the same distance aged 0-5 years had a fivefold increase in risk (OR 4.74; 0.98-22.9). These associations were strengthened when analyses were repeated for 201 pairs with entirely Tasmanian residential histories. CONCLUSION: Although recognizing that this study has limitations, the results raise the possibility that prolonged residence close to high-voltage power lines, especially early in life, may increase the risk of the development of MPD and LPD later.


Assuntos
Fontes de Energia Elétrica/efeitos adversos , Campos Eletromagnéticos/efeitos adversos , Exposição Ambiental/efeitos adversos , Transtornos Linfoproliferativos/epidemiologia , Transtornos Mieloproliferativos/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Transtornos Linfoproliferativos/etiologia , Transtornos Mieloproliferativos/etiologia , Fatores de Risco , Tasmânia/epidemiologia , Fatores de Tempo
9.
Cytotherapy ; 9(2): 158-64, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17453967

RESUMO

BACKGROUND: Harvesting of hemopoietic stem cells (HSC) from G-CSF-primed BM for autologous transplantation is an alternative to collection of unprimed BM or G-CSF-primed peripheral blood (PB). However, the optimum number of days of G-CSF administration for this purpose is unknown. We set out to determine whether cell yields could be optimized by varying the number of days of G-CSF administration prior to BM stem cell harvesting. METHODS: We conducted a randomized controlled single-center trial of 6 days (the standard) vs. 4 days of G-CSF administration and compared yields of total nucleated cells (TNC), CD34(+) HSC and CFU-GM cells per kilogram patient body weight. Statistical analysis was by Student's t-test. RESULTS: Twenty-four patients were enrolled; 13 received 6 days and 11 received 4 days of G-CSF administration. Analysis of the first harvest aspirate showed higher proportions of CD34(+) HSC (P=0.02) and CFU-GM (P=0.03) in the 4-day group. For the 6-day and 4-day groups, respectively, the median yield of TNC/kg was 6.5 x 10(8) and 5.4 x 10(8) (P=0.28), of CD34(+) cells/kg 0.56 x 10(6) and 0.98 x 10(6) (P=0.04) and of CFU-GM cells/kg 1.66 x 10(5) and 1.55 x 10(5) (P=0.75). DISCUSSION: These results suggest that by 6 days the HSC-stimulating effect of G-CSF has passed its peak and that 4 days should be adopted as the standard for G-CSF priming prior to BM stem cell harvesting for autologous transplantation.


Assuntos
Transplante de Medula Óssea/métodos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Adolescente , Adulto , Idoso , Antígenos CD34/metabolismo , Separação Celular/métodos , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Transplante Autólogo
10.
J Clin Neurosci ; 13(6): 677-81, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16815020

RESUMO

Extracranial metastases of glioblastoma multiforme (GBM) are rare and usually occur in the context of recurrent intracranial GBM. We present a 39-year-old man with histologically confirmed GBM. The patient remained well for nearly 2 years, with no signs of recurrent tumour. He then presented with distant recurrence within the brain at the same time as developing pneumonia and epigastric pain. A computed tomography scan of the patient's abdomen and chest showed several intra-abdominal masses, including one in the head of the pancreas as well as a separate mass at the base of the left lung. A computed tomography-guided biopsy of the pancreatic mass demonstrated histological appearances identical to those of the original GBM. This unusual case raises the possibility of a link between prolonged survival with GBM and the occurrence of extracranial disease.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Neoplasias Intestinais/metabolismo , Metástase Neoplásica , Neoplasias Pancreáticas/secundário , Neoplasias Pleurais/secundário , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imuno-Histoquímica/métodos , Neoplasias Intestinais/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Neoplasias Pancreáticas/diagnóstico por imagem , Fosfopiruvato Hidratase/metabolismo , Neoplasias Pleurais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
11.
J Clin Neurosci ; 13(3): 384-5, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16497503

RESUMO

Complications of bone marrow trephine are thought to be uncommon. Herein, we present a case of severe debilitating sciatic nerve palsy secondary to a gluteal artery pseudoaneurysm following bone marrow biopsy. The pseudoaneurysm was treated successfully by percutaneous embolization; however, the patient remains significantly impaired with persistent painless foot drop.


Assuntos
Falso Aneurisma/diagnóstico , Exame de Medula Óssea/efeitos adversos , Fadiga/etiologia , Artéria Ilíaca , Neuropatia Ciática/etiologia , Falso Aneurisma/terapia , Exame de Medula Óssea/métodos , Embolização Terapêutica , Feminino , Humanos , Pessoa de Meia-Idade
12.
Methods Find Exp Clin Pharmacol ; 27(10): 705-10, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16395421

RESUMO

We have developed an antibody-based method to assess plasma uptake of a proprietary Undaria-derived fucoidan galactofucan sulfate (GFS(TM)) after oral ingestion by human volunteers. Fucoidans have high-molecular-weights but exert biological effects in experimental animals after oral intake. By using a novel antibody raised against sulfated polysaccharides, we carried out a competitive ELISA to quantitate GFS in plasma samples from healthy volunteers who ingested 3 g/day of whole Undaria containing 10% GFS fucoidan, purified 75% GFS fucoidan, or 3 g of a nonsulfated placebo polysaccharide over 12 days. Increased reactivity to the novel antibody, as measured against preingestion levels, was detected at all time points. Assuming the measured material to be intact GFS, the concentration detected (median) was 4.002 and 12.989 mg/l when 3 g of 10% or 75% pure fucoidan was ingested orally over a period of 12 days, respectively. High-molecular-weight fucoidan can be detected in plasma using an ELISA competitive assay based on a novel antibody to sulfated polysaccharides.


Assuntos
Anticoagulantes/farmacocinética , Ensaio de Imunoadsorção Enzimática/métodos , Polissacarídeos/farmacocinética , Adulto , Anticorpos Monoclonais , Anticoagulantes/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissacarídeos/sangue
13.
Apoptosis ; 7(5): 387-94, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12207171

RESUMO

Whilst the role of ceramide, a second messenger of the sphingolipid family, in the initiation of receptor-mediated apoptosis is controversial, a growing body of evidence is emerging for a role of ceramide in the amplification of apoptosis via mitochondrial perturbations that culminate in the activation of execution caspases. Treatment of Jurkat T cells with the cell-permeable analog, C(2)-ceramide, resulted in the rapid onset of apoptosis as evidenced by Annexin V-FITC staining of externalised phosphatidylserine residues. Cells bearing this early apoptotic marker had a reduced mitochondrial transmembrane potential (Delta(Psi)m) that was preceded by the release of cytochrome c from mitochondria. Subsequent activation of caspase-3 provides the link between these ceramide-induced mitochondrial changes and execution caspases that ultimately result in the physical destruction of the cell. Collectively these results demonstrate that ceramide signalling results in caspase-mediated apoptosis via mitochondrial cytochrome c release and are further supportive of the role of ceramide in the amplification of apoptosis.


Assuntos
Apoptose/fisiologia , Caspases/metabolismo , Ceramidas/metabolismo , Grupo dos Citocromos c/metabolismo , Células Eucarióticas/metabolismo , Membranas Intracelulares/metabolismo , Mitocôndrias/metabolismo , Esfingosina/análogos & derivados , Anexina A5/metabolismo , Apoptose/efeitos dos fármacos , Caspase 3 , Células Eucarióticas/citologia , Células Eucarióticas/efeitos dos fármacos , Fluoresceína-5-Isotiocianato , Humanos , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/ultraestrutura , Células Jurkat , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Fosfatidilserinas/metabolismo , Esfingosina/farmacologia
14.
Bone Marrow Transplant ; 28(10): 929-33, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11753546

RESUMO

We studied interleukin-6 (IL-6) levels on the day of transplantation in 31 patients undergoing autologous haemopoietic stem cell transplantation (SCT) (either peripheral blood stem cell transplantation (PBSCT) or bone marrow transplantation (BMT)) for neoplastic diseases to determine if there was a relationship between IL-6 level and rate of haemopoietic recovery, length of stay in hospital, and survival. There was no apparent delay in post-transplant recovery associated with elevated IL-6 levels. However, increased values of IL-6 tended to be associated with an increased length of stay in hospital (P = 0.083). There was a highly significant adverse association between higher IL-6 levels and survival following transplantation (P = 0.0001). This association remained significant (P = 0.013) in the uniform subgroup of patients with malignant lymphoma with chemosensitive disease who had undergone BMT (that is, excluding patients who had undergone PBSCT) (n = 13). Knowledge of IL-6 levels on the day of transplant has the potential to provide valuable prognostic information in patients undergoing autologous haemopoietic SCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Interleucina-6/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/mortalidade , Neoplasias/terapia , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Transplante Autólogo/efeitos adversos , Transplante Autólogo/mortalidade , Resultado do Tratamento
15.
Br J Haematol ; 113(3): 727-36, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11380464

RESUMO

Patterns of failure were studied in two consecutive randomized trials of intensified induction therapy carried out by the Australian Leukaemia Study Group (ALSG) between 1984 and 1991 to determine the impact of dose intensification. Patients received standard dose cytarabine and daunorubicin (7-3), 7-3 plus etoposide (7-3-7) or 7-3 plus high-dose cytarabine (HIDAC-3-7) chemotherapy. Patients with FAB M3 morphology were excluded. Time to failure (TTF) was defined as the time from randomization to induction death or removal from study for non-responders, or to relapse or death in complete response (CR) for complete responders. An estimated 86% of 470 de novo patients with acute myeloid leukaemia failed within 10 years of randomization, as a result of death in induction in 17% of the randomized patients, failure to achieve CR in a further 17%, relapse in 44% and death in CR in 8% of patients. An estimated 66% of patients failed as a result of refractory disease or relapse within that period (disease-related failures). Multifactor analysis identified age and peripheral blast count as the most significant pretreatment factors associated with overall TTF. These factors, together with cytogenetics, were significantly associated with disease-related failures. High-dose cytarabine in induction significantly decreased the disease-related failure rate as did allogeneic transplantation in first CR. The impact of high-dose cytarabine did not depend on the cytogenetic risk group.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Medição de Risco , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Austrália , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Etoposídeo/administração & dosagem , Humanos , Incidência , Leucemia Mieloide/mortalidade , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Taxa de Sobrevida , Fatores de Tempo , Falha de Tratamento
16.
Leuk Lymphoma ; 41(1-2): 197-201, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11342374

RESUMO

Pathologic splenic rupture in non-Hodgkin's lymphoma (NHL) is a rare event, with 32 cases previously reported. Initial presentation of NHL with this complication is even rarer. We report such a case in an 80-year-old man with mantle cell lymphoma (MCL). It is notable that of the previously reported cases of pathologic rupture, three have occurred in MCL, suggesting that patients with this uncommon subtype of NHL may be particularly vulnerable to pathologic splenic rupture. Following splenectomy the patient's disease behaved in a high-grade fashion. Despite an initially encouraging response, his disease ran an aggressive course and he succumbed within four months. This case demonstrates the presentation of MCL with pathologic splenic rupture, as well as the potentially highly malignant behaviour of the disease.


Assuntos
Linfoma de Célula do Manto/diagnóstico , Ruptura Esplênica/patologia , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Evolução Fatal , Humanos , Linfoma de Célula do Manto/complicações , Linfoma de Célula do Manto/patologia , Masculino , Esplenectomia , Ruptura Esplênica/diagnóstico
17.
Cytometry ; 43(3): 164-9, 2001 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11170101

RESUMO

BACKGROUND: Leukaemia cells differ from their normal counterparts in that their ability to properly regulate survival, proliferation, differentiation, and apoptosis is aberrant. Understanding the molecular mechanisms controlling cell proliferation and developing therapeutic strategies to correct nonfunctional regulatory mechanisms are emerging areas of medical research. Ceramide, a metabolite of membrane sphingomyelin hydrolysis, has recently emerged as a key regulator of cellular proliferation, differentiation, and apoptosis in leukaemia cells. METHODS: Leukaemia cell lines were treated with a biologically active analogue of ceramide, C(2)-ceramide. Cell cycle status was assessed flow cytometrically using propidium iodide. Induction of apoptosis was confirmed by annexin V staining of externalised phosphatidylserine and retinoblastoma activation was determined by Western blotting. RESULTS: C(2)-ceramide induced activation of retinoblastoma tumour suppressor protein, G(0)/G(1) cell cycle arrest, or apoptosis in leukaemia cell lines. In addition, these effects differed depending upon cell type, thus confirming the pleiotropic nature of the ceramide signalling pathway. Most cells studied responded to exogenous C(2)-ceramide by entering growth arrest, evidently resulting from activation of retinoblastoma protein, and by displaying some degree of apoptosis. CONCLUSIONS: Taken together, these findings suggest that signalling via ceramide has novel therapeutic applications for treatment of leukaemia.


Assuntos
Ciclo Celular/fisiologia , Células-Tronco Hematopoéticas/citologia , Proteína do Retinoblastoma/metabolismo , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Ciclo Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Citometria de Fluxo/métodos , Fase G1 , Células HL-60 , Humanos , Células Jurkat , Leucemia , Fosforilação , Fase de Repouso do Ciclo Celular , Proteína do Retinoblastoma/efeitos dos fármacos , Células Tumorais Cultivadas , Células U937
19.
J Clin Immunol ; 20(1): 17-23, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10798603

RESUMO

Based on animal models and limited clinical experience, there is considerable interest in use of high-dose immunosuppression followed by hemopoietic stem cell transplantation as treatment for severe rheumatoid arthritis. Because of its relatively low treatment-related mortality and morbidity, autologous transplantation is a more attractive option than allogeneic transplantation for initial clinical trials, even though anecdotal reports suggest that allogeneic transplantation has a greater likelihood of bringing about long-term disease control. The approach remains experimental with many unanswered questions such as the value and safety of high-dose therapy without transplantation, the need for T cell purging, the possible deleterious effects of post-transplant hemopoietic growth factors and the potential of "mini" allogeneic transplantation (a process whereby intense immunosuppression is combined with less intense myelosuppression). To achieve quick progress it is essential that clinical trials be carefully designed with all cases being reported to the Autoimmune Disease Stem Cell Project Database.


Assuntos
Artrite Reumatoide/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Criança , Pré-Escolar , Humanos , Recém-Nascido
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...