RESUMO
l-asparaginase encapsulated within erythrocytes (GRASPA(®) ) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA(®) for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse. Between February 2006 and April 2008, 18 patients received GRASPA(®) (50 iu/kg: n = 6,100 iu/kg: n = 6, 150 iu/kg: n = 6) after randomization, and six patients were assigned to the Escherichia coli native l-asparaginase (E. colil-ASNase) control group. GRASPA(®) was effective at depleting l-asparagine. One single injection of 150 iu/kg of GRASPA(®) provided similar results to 8 × 10,000 iu/m(2) intravenous injections of E. colil-ASNase. The safety profile of GRASPA(®) showed a reduction in the number and severity of allergic reactions and a trend towards less coagulation disorders. Other expected adverse events were comparable to those observed with E. colil-ASNase and there was also no difference between the three doses of GRASPA(®) .
Assuntos
Antineoplásicos/administração & dosagem , Asparaginase/administração & dosagem , Portadores de Fármacos , Eritrócitos/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/sangue , Antineoplásicos/uso terapêutico , Asparaginase/efeitos adversos , Asparaginase/sangue , Asparaginase/uso terapêutico , Reatores Biológicos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Sistemas de Liberação de Medicamentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Adulto JovemRESUMO
There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high-quality cancer care. European policy (EU Cancer Mission and Europe's Beating Cancer Plan) is currently moving towards a mission-oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes' Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high-impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals.
Assuntos
Institutos de Câncer , Neoplasias/terapia , Qualidade da Assistência à Saúde , Academias e Institutos/normas , Academias e Institutos/estatística & dados numéricos , Pesquisa Biomédica/organização & administração , Pesquisa Biomédica/normas , Pesquisa Biomédica/estatística & dados numéricos , Institutos de Câncer/organização & administração , Institutos de Câncer/estatística & dados numéricos , Estudos de Coortes , Europa (Continente)/epidemiologia , Humanos , Oncologia/normas , Oncologia/estatística & dados numéricos , Neoplasias/epidemiologia , Equipe de Assistência ao Paciente/organização & administração , Equipe de Assistência ao Paciente/normas , Equipe de Assistência ao Paciente/estatística & dados numéricos , Assistência Centrada no Paciente/organização & administração , Assistência Centrada no Paciente/normas , Assistência Centrada no Paciente/estatística & dados numéricos , Pesquisa Translacional Biomédica/métodos , Pesquisa Translacional Biomédica/organização & administração , Pesquisa Translacional Biomédica/estatística & dados numéricosRESUMO
PURPOSE: A phase I/II trial was conducted to evaluate clinical and immunologic responses after intralymphatic and intranodal injections of mature dendritic cells. EXPERIMENTAL DESIGN: Fourteen patients with a metastatic melanoma received matured dendritic cells, loaded with Melan-A/MART-1 and/or NA17-A peptides and keyhole limpet hemocyanin. The cells were matured overnight with Ribomunyl, a toll-like receptor ligand, and IFN-gamma, which ensured the production of high levels of interleukin-12p70. Dendritic cells were injected at monthly intervals, first into an afferent lymphatic and then twice intranodally. Immunologic responses were monitored by tetramer staining of circulating CD8(+) lymphocytes and delayed-type hypersensitivity tests. RESULTS: Dendritic cell vaccination induced delayed-type hypersensitivity reactivity toward NA17-A-pulsed, keyhole limpet hemocyanin-pulsed, and Melan-A-pulsed dendritic cells in 6 of 10, 4 of 11, and 3 of 9 patients, respectively. Four of the 12 patients analyzed by tetramer staining showed a significantly increased frequency of Melan-A-specific T cells, including one patient vaccinated only with NA17-A-pulsed dendritic cells. Furthermore, 2 of the 12 analyzed patients had a significant increase of NA17-A-specific T cells, including one immunized after an optional additional treatment course. No objective clinical response was observed. Two patients were stabilized at 4 and 10 months and three patients are still alive at 30, 39, and 48 months. CONCLUSIONS: Injections into the lymphatic system of mature peptide-loaded dendritic cells with potential TH1 polarization capacities did not result in marked clinical results, despite immunologic responses in some patients. This highlights the need to improve our understanding of dendritic cell physiology.
Assuntos
Células Dendríticas/transplante , Imunoterapia Adotiva/métodos , Melanoma/terapia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Formação de Anticorpos , Antígenos de Neoplasias/química , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/análise , Vacinas Anticâncer/uso terapêutico , Células Dendríticas/química , Intervalo Livre de Doença , Feminino , Humanos , Imunidade Celular , Imunoterapia Adotiva/efeitos adversos , Injeções Intralinfáticas/métodos , Metástase Linfática/imunologia , Metástase Linfática/patologia , Antígeno MART-1 , Masculino , Melanoma/imunologia , Melanoma/mortalidade , Pessoa de Meia-Idade , Proteínas de Neoplasias/química , Proteínas de Neoplasias/imunologia , Peptídeos/química , Peptídeos/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Electronic health records (EHR) are increasingly being adopted by healthcare systems worldwide. In France, the "Hôpital numérique 2012-2017" program was implemented as part of a strategic plan to modernize health information technology (HIT), including promotion of widespread EHR use. With significant upfront investment costs as well as ongoing operational expenses, it is important to assess this system in terms of its ability to result in improvements in hospital performances. The aim of this study was to evaluate the impact of EHR use on the organizational performances of acute care hospital surgical units throughout France. METHODS: This retrospective study was based on data derived from three national databases for year the 2012: IPAQSS (Indicators of improvement in the quality and the management of healthcare, "IPAQSS"), Hospi-Diag (French hospital performance indicators), and the national accreditation database. National data and methodological support were provided by the French Ministry of Health (DGOS) and the French National Authority for Health (HAS). Multivariate linear models were used to assess four organizational performance indicators: the occupancy rate of surgical inpatient beds, operating room utilization, the activity per surgeon, and the activity per both nurse anesthetist and anesthesiologist which were dependent variables. Several independent variables were taken into account, including the degree of EHR use. RESULTS: The models revealed a significant positive impact of EHR use on operating room utilization and bed occupancy rates for surgical inpatient units. No significant association was found between the activity per surgeon or the activity per nurse anesthetist and anesthesiologist with EHR use. All four organizational performance indicators were impacted by the type of hospital, the geographical region, and the severity of the pathologies. CONCLUSION: We were able to verify the purported potential benefits of EHR use on the organizational performances of surgical units in French hospitals.
Assuntos
Atenção à Saúde/organização & administração , Registros Eletrônicos de Saúde/estatística & dados numéricos , Informática Médica/organização & administração , Cultura Organizacional , Centro Cirúrgico Hospitalar , Estudos Transversais , França , Humanos , Equipe de Assistência ao Paciente , Estudos RetrospectivosRESUMO
BACKGROUND: Electronic health records (EHR) are increasingly being adopted by healthcare systems worldwide. In France, the "Hôpital numérique 2012-2017" program was implemented as part of a strategic plan to modernize health information technology (HIT), including the promotion of widespread EHR use. With significant upfront investment costs as well as ongoing operational expenses, it is important to assess this system in terms of its ability to result in improvements in hospital performances. OBJECTIVE: The aim of this study was to evaluate the impact of EHR use on the quality of care management in acute care hospitals throughout France. METHODS: This retrospective study was based on data derived from three national databases for the year 2011: IPAQSS (indicators of improvement in the quality and the management of healthcare, "IPAQSS"), Hospi-Diag (French hospital performance indicators), and the national accreditation database. Several multivariate models were used to examine the association between the use of EHRs and specific EHR features with four quality indicators: the quality of patient record, the delay in sending information at hospital discharge, the pain status evaluation, and the nutritional status evaluation, while also adjusting for hospital characteristics. RESULTS: The models revealed a significant positive impact of EHR use on the four quality indicators. Additionally, they showed a differential impact according to the functionality of the element of the health record that was computerized. All four quality indicators were also impacted by the type of hospital, the geographical region, and the severity of the pathology. CONCLUSION: These results suggest that, to improve the quality of care management in hospitals, EHR adoption represents an important lever. They complete previous work dealing with EHR and the organizational performance of hospital surgical units.
Assuntos
Atenção à Saúde/organização & administração , Registros Eletrônicos de Saúde/estatística & dados numéricos , Hospitais/normas , Informática Médica/normas , Equipe de Assistência ao Paciente , Qualidade da Assistência à Saúde , Estudos Transversais , França , Humanos , Estudos RetrospectivosRESUMO
This study compares the cryopreservation of PBSC by means of HES 3% + DMSO 5% ina mechanical freezer with the cryopreservation of PBSC by means of DMSO 10% in an automated rate controlled freezer. The cells harvested from the same patient were divided in two equal parts and frozen according to both methods. Cryopreservation with HES +DMSO is better than DMSO alone in terms of viability (p<0.001) and Granulocyte Macrophage Colony Forming Unit (GM-CFU) activity (p<0.05). The freezing curves differ essentially in the slope down after the surfusion peak. However, surfusion peaks are similar in both conditions. The relevance of mechanical freezing is the saving of time and the safety of such a procedure.
Assuntos
Criopreservação/métodos , Crioprotetores , Dimetil Sulfóxido , Células-Tronco Hematopoéticas , Derivados de Hidroxietil Amido , Protocolos de Quimioterapia Combinada Antineoplásica , Contagem de Colônia Microbiana , HumanosRESUMO
BACKGROUND: Cancer patients with CD4 lymphopenia have an increased risk of severe toxicity after administration of cytotoxic chemotherapy. The impact of CD4 lymphopenia on long term overall survival (OS) of cancer patients was explored in this work. PATIENTS AND METHODS: The first prospective series (test series) included 219 patients with solid tumours, lymphomas or myelomas receiving chemotherapy within an oncology department in 1999 and 2000. A phenotypic analysis of lymphocyte subsets by flow cytometry was performed before chemotherapy on day 1. The prognostic value of total, CD4, CD8 and CD56 lymphocyte count for OS was tested in a multivariate analysis. The prognostic value of low CD4 counts was then tested in a validation series of 269 patients with metastatic solid tumours in second line treatment included in a prospective observational study in the Centre Leon Berard. RESULTS: In the test series, all patients with metastatic cancers and CD4 lymphopenia ≤ 200/µL (12% of metastatic patients) died within 18 months with a median OS of 5.9 months. CD4 count was an independent prognostic factor for OS and PFS in multivariate analysis. In the validation series, 83 (30%) of patients had CD4 count ≤ 200/µL: their median overall survival was 3.9 months with an 18-month survival rate of 6%. CD4 count was also an independent prognostic factor for overall survival in this series. CONCLUSIONS: CD4 lymphopenia <200/µL is frequent in advanced cancer patients and associated with a very short life expectancy. These patients should be proposed for specific treatment and research approaches.
Assuntos
Linfócitos T CD4-Positivos/patologia , Linfopenia/diagnóstico , Neoplasias/diagnóstico , Neoplasias/mortalidade , Idoso , Idoso de 80 Anos ou mais , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/fisiologia , Feminino , Humanos , Incidência , Linfopenia/epidemiologia , Linfopenia/etiologia , Linfopenia/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/complicações , Neoplasias/patologia , Prognóstico , Análise de Sobrevida , Taxa de SobrevidaAssuntos
Antineoplásicos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Leucemia Mieloide de Fase Crônica/cirurgia , Transplante de Células-Tronco de Sangue Periférico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Transplante Autólogo , Adulto , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Benzamidas , Terapia Combinada , Citarabina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Mesilato de Imatinib , Interferons/uso terapêutico , Lenograstim , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/genética , Masculino , Piperazinas/farmacologia , Pirimidinas/farmacologia , Proteínas Recombinantes/farmacologia , Indução de RemissãoRESUMO
Randomized trials have demonstrated improved outcome from adding rituximab to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) for patients with diffuse large B-cell lymphoma (DLBCL). This retrospective study compared the outcomes of 224 patients with DLBCL treated in our institution before (Period 1, 1996-2002) and after (Period 2, 2002-2005) approval of rituximab in this indication to evaluate the impact of the drug in daily practice in unselected patients receiving different types of chemotherapy. We treated 131 patients in Period 1 versus 93 in Period 2 (median follow-up, 75 and 29 months, respectively) with no difference in patient characteristics between the two periods. Event-free and overall survivals (EFS and OS) were significantly improved in Period 2 for elderly patients and a significant shift in the selection of regimens was observed at the time when rituximab became available. More patients received the CHOP regimen in Period 2 than in Period 1 (82 vs. 57%, p < 0.007) with CHOP being substituted for epirubicin-based regimens. In younger patients treated mostly with the ACVBP regimen (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) these differences were not observed, suggesting that combination of rituximab with dose-dense chemotherapy may deserve further evaluation in this age group.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , RituximabRESUMO
PURPOSE: gamma9delta2 T lymphocytes have been shown to be directly cytotoxic against renal carcinoma cells. Lymphocytes T gammadelta can be selectively expanded in vivo with BrHPP (IPH1101, Phosphostim) and interleukin 2 (IL-2). A phase I Study was conducted in patients with metastatic renal cell carcinoma (mRCC) to determine the maximum-tolerated dose and safety of Innacell gammadelta, an autologous cell-therapy product based on gamma9delta2 T lymphocytes, in patients with mRCC. EXPERIMENTAL DESIGN: A 1-h intravenous infusion of gamma9delta2 T lymphocytes was administered alone during treatment cycle 1 and combined with a low dose of subcutaneous interleukin-2 (IL-2, 2 MIU/m2 from Day 1 to Day 7) in the two subsequent cycles (at 3-week intervals). The dose of gamma9delta2 T lymphocytes was escalated from 1 up to 8 x 10(9) cells. RESULTS: Ten patients underwent a total of 27 treatment cycles. Immunomonitoring data demonstrate that gamma9delta2 T lymphocytes are initially cleared from the blood to reappear at the end of IL-2 administration. Dose-limiting toxicity occurred in one patient at the dose of 8 x 10(9) cells (disseminated intravascular coagulation). Other treatment-related adverse events (AEs) included mainly gastrointestinal disorders and flu-like symptoms (fatigue, pyrexia, rigors). Hypotension and tachycardia also occurred, especially with co-administered IL-2. Six patients showed stabilized disease. Time to progression was 25.7 weeks. CONCLUSION: The data collected in ten patients with mRCC indicate that repeated infusions of Innacell gammadelta at different dose levels (up to 8 x 10(9) total cells), either alone or with IL-2 is well tolerated. These results are in favor of the therapeutic value of cell therapy with Innacell gammadelta for the treatment of cancers.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/terapia , Imunoterapia , Interleucina-2/uso terapêutico , Neoplasias Renais/terapia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/secundário , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
During the last two decades, improvements in the induction and consolidation treatment phases in patients with high-risk neuroblastoma have not translated into significant increases in survival rates. Efforts to improve outcome have used high-dose chemotherapy with stem cell rescue and more recently, differentiating (retinoids) and antiangiogenic agents. In parallel, immunotherapy has become an increasingly important part of the treatment of high-risk neuroblastoma. We review here the biological concepts underlying these new approaches and their clinical applications, with a particular emphasis on applications that manipulate the immune system, including monoclonal antibodies, gene-modified tumor cells (vaccines) or immune effectors.
Assuntos
Imunoterapia , Neuroblastoma/terapia , Criança , Ensaios Clínicos como Assunto , Humanos , Imunoterapia/métodos , Neuroblastoma/imunologia , PrognósticoRESUMO
BACKGROUND: Lymphopenia is frequently observed in patients with cancer and correlates with the risk of febrile neutropenia and early death after chemotherapy. The phenotype of the depleted lymphocyte populations was investigated in the current study. METHODS: Peripheral blood lymphocyte subsets (CD3, CD4, CD8, CD19, CD56) were quantified on Day 1 using fluorescence-activated cell sorting in a prospective study of 213 patients with cancer treated with chemotherapy in a single oncology ward during 12 months. Correlations between lymphocyte phenotype, clinical characteristics, and the risk of febrile neutropenia and early death within 31 days after chemotherapy were investigated in univariate and multivariate analyses. RESULTS: Total lymphocyte count and CD3, CD4, and CD8 lymphocyte subsets were significantly lower in patients who experienced febrile neutropenia. Total lymphocyte count and CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were significantly lower in patients who died within 31 days after chemotherapy. Using logistic regression, CD4 lymphopenia (< 450/muL; odds ratio [OR] = 2.9, 95% confidence interval [CI] = 1.5-5.9) and the dose of chemotherapy (OR = 3,9, 95% CI = 2.0-7.8) were both identified as independent risk factors for febrile neutropenia. Fifty-four percent of patients with both risk factors experienced febrile neutropenia. CD4 lymphocyte count < 450/muL was also an independent risk factor for early death (OR = 7.7, 95% CI = 1.7-35). Thirteen percent of patients with a CD4 lymphocyte count = 450/muL died within 31 days after chemotherapy. Eighty-seven percent (14 of 16) of patients who died before Day 31 had a CD4 lymphocyte count < 450/muL. CONCLUSIONS: A low CD4 count was an independent risk factor for febrile neutropenia and early death in patients receiving cytotoxic chemotherapy.