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1.
Haematologica ; 104(1): 147-154, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30115656

RESUMO

Lenalidomide has been proven to be effective but with a distinct and difficult to manage toxicity profile in the context of chronic lymphocytic leukemia, potentially hampering combination treatment with this drug. We conducted a phase 1-2 study to evaluate the efficacy and safety of six cycles of chlorambucil (7 mg/m2 daily), rituximab (375 mg/m2 cycle 1 and 500 mg/m2 cycles 2-6) and individually-dosed lenalidomide (escalated from 2.5 mg to 10 mg) (induction-I) in first-line treatment of patients with chronic lymphocytic leukemia unfit for treatment with fludarabine, cyclophosphamide and rituximab. This was followed by 6 months of 10 mg lenalidomide monotherapy (induction-II). Of 53 evaluable patients in phase 2 of the study, 47 (89%) completed induction-I and 36 (68%) completed induction-II. In an intention-to-treat analysis, the overall response rate was 83%. The median progression-free survival was 49 months, after a median follow-up time of 27 months. The 2- and 3-year progression-free survival rates were 58% and 54%, respectively. The corresponding rates for overall survival were 98% and 95%. No tumor lysis syndrome was observed, while tumor flair reaction occurred in five patients (9%, 1 grade 3). The most common hematologic toxicity was grade 3-4 neutropenia, which occurred in 73% of the patients. In conclusion, addition of lenalidomide to a chemotherapy backbone followed by a fixed duration of lenalidomide monotherapy resulted in high remission rates and progression-free survival rates, which seem comparable to those observed with novel drug combinations including novel CD20 monoclonal antibodies or kinase inhibitors. Although lenalidomide-specific toxicity remains a concern, an individualized dose-escalation schedule is feasible and results in an acceptable toxicity profile. EuraCT number: 2010-022294-34.

2.
Hematol Oncol ; 35(4): 497-503, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27530779

RESUMO

The prognosis of central nervous system (CNS) relapse of systemic non-Hodgkin lymphoma is poor with 1-year survival historically at 0% to 20%. Aiming to improve these results, we performed a multicenter phase 2 study in patients with a CNS relapse, with or without concurrent systemic relapse. Treatment consisted of 2 cycles of R-DHAP alternating with high-dose methotrexate (MTX) and was combined with intrathecal rituximab. Responding patients received a third R-DHAP-MTX cycle followed by busulfan and cyclophosphamide myeloablative therapy and autologous stem cell transplantation. In patients with persistent cerebrospinal fluid lymphoma after cycle 1, the intrathecal rituximab was replaced by intrathecal triple therapy, with MTX, cytarabine, and dexamethasone. Thirty-six patients were included. Eighteen had evidence of cerebrospinal fluid lymphoma, 24 had brain parenchymal disease, and 20 (56%) had concurrent systemic disease. The overall response rate after 2 R-DHAP-MTX was 53% (19/36), with 22% (8/36) complete remission. Fifteen patients (42%) underwent a transplant. One-year progression-free survival was 19% (95% confidence interval, 9-34): 25% in patients without and 15% in patients with systemic disease. One-year overall survival was 25% (95% confidence interval, 12-40). This treatment regimen did not result in a major improvement of outcome of secondary CNS lymphoma, especially when concurrent systemic disease was present. Registered in the Dutch trial register www.trialregister.nl, NTR1757; EudraCT number 2006-002141-37.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/tratamento farmacológico , Metotrexato/uso terapêutico , Rituximab/uso terapêutico , Transplante Autólogo/métodos , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/patologia , Cisplatino/uso terapêutico , Citarabina/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
3.
Opt Express ; 23(19): 24440-55, 2015 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-26406649

RESUMO

We demonstrate experimentally the enhanced THz extinction by periodic arrays of resonant semiconductor particles. This phenomenon is explained in terms of the radiative coupling of localized resonances with diffractive orders in the plane of the array (Rayleigh anomalies). The experimental results are described by numerical calculations using a coupled dipole model and by Finite-Difference in Time-Domain simulations. An optimum particle size for enhancing the extinction efficiency of the array is found. This optimum is determined by the frequency detuning between the localized resonances in the individual particles and the Rayleigh anomaly. The extinction calculations and measurements are also compared to near-field simulations illustrating the optimum particle size for the enhancement of the near-field.

4.
Am J Hematol ; 89(4): 355-62, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24273190

RESUMO

Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six elderly (>65 years) newly diagnosed MM patients from six European randomized trials were retrospectively analyzed and matched for age, albumin, and beta2-microglobulin at diagnosis, 296 patients were selected from the VMP groups, and 294 from MPT. Complete response rate was 21% in the VMP patients and 13% in the MPT patients (P = 0.007). After a median follow-up of 34 months (range, 1-92), VMP significantly prolonged both PFS (median 32.5 vs. 22.9 months, HR 0.65; 95% CI 0.52-0.82; P < 0.001) and OS (median 79.7 vs. 45.1 months, HR 0.44; 95% CI 0.32-0.59; P < 0.001) in comparison with MPT. The benefit in terms of OS of the VMP group was quite similar among patients with different risk factors defined by sex, ISS, ECOG performance status, or serum creatinine but not among patients ≥ 75 years. Multivariate analysis confirmed that VMP was an independent predictor of longer PFS and OS. In a control-case matched analysis, PFS and OS were prolonged in patients who received VMP in comparison with those treated with MPT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/efeitos adversos , Bortezomib , Estudos de Casos e Controles , Intervalo Livre de Doença , Avaliação de Medicamentos , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Doenças do Sistema Nervoso/induzido quimicamente , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prognóstico , Modelos de Riscos Proporcionais , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Resultado do Tratamento
5.
Haematologica ; 98(6): 980-7, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23445873

RESUMO

Thalidomide and bortezomib are extensively used to treat elderly myeloma patients. In these patients, treatment-related side effects are frequent and full drug doses difficult to tolerate. We retrospectively analyzed data from 1435 elderly patients enrolled in 4 European phase III trials including thalidomide and/or bortezomib. After a median follow up of 33 months (95%CI: 10-56 months), 513 of 1435 patients (36%) died; median overall survival was 50 months (95%CI: 46-60 months). The risk of death was increased in patients aged 75 years or over (HR 1.44, 95%CI: 1.20-1.72; P<0.001), in patients with renal failure (HR 2.02, 95%CI: 1.51-2.70; P<0.001), in those who experienced grade 3-4 infections, cardiac or gastrointestinal adverse events during treatment (HR 2.53, 95%CI: 1.75-3.64; P<0.001) and in those who required drug discontinuation due to adverse events (HR 1.67, 95%CI; 1.12-2.51; P=0.01). This increased risk was restricted to the first six months after occurrence of adverse events or drug discontinuation and declined over time. More intensive approaches, such as the combination of bortezomib-thalidomide, negatively affected outcome. Bortezomib-based combinations may overcome the negative impact of renal failure. Age 75 years or over or renal failure at presentation, occurrence of infections, cardiac or gastrointestinal adverse events negatively affected survival. A detailed geriatric assessment, organ evaluation and less intense individualized approaches are suggested in elderly unfit subjects.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Mieloma Múltiplo/mortalidade , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Causas de Morte , Feminino , Humanos , Masculino , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
6.
Haematologica ; 98(1): 87-94, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22875621

RESUMO

Treatment with melphalan-prednisone-thalidomide improves the outcome of patients with multiple myeloma and is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. A meta-analysis of data from individual patients (n=1680) in six randomized trials was performed, comparing the effects of melphalan-prednisone-thalidomide versus melphalan-prednisone. The main objective was to estimate the risk of serious adverse events and their impact on outcome. The primary endpoints were the 2-year cumulative incidence of grade 3-4 hematologic and non-hematologic toxicities. At least 75% of the grade 3-4 toxicities occurred during the first 6 months of treatment in both treatment groups. The cumulative incidence of grade 3-4 hematologic toxicities was higher in the melphalan-prednisone-thalidomide group than in the melphalan-prednisone group (28% versus 22%; HR 1.32, 95% CI 1.05-1.66) as was the cumulative incidence of non-hematologic toxicities (39% versus 17%, HR 2.78, 95% CI 2.21-3.50). Grade 3-4 non-hematologic toxicities were significantly increased in patients with poor Performance Status. Occurrence of grade 3-4 non-hematologic toxicities had a negative impact on both progression-free survival (HR 1.24, 95% CI 1.07-1.45) and overall survival, (HR 1.23, 95% CI 1.03-1.47). Besides toxicities, progression-free and overall survival were also negatively affected by advanced International Staging System stage, high creatinine levels and poor Performance Status. Age had a negative impact on survival as well. Although melphalan-prednisone-thalidomide improved outcome, it increased toxicities, especially non-hematologic ones. Serious non-hematologic toxicities, older age, poor Performance Status, and high creatinine levels negatively affected survival.


Assuntos
Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/diagnóstico , Humanos , Masculino , Mieloma Múltiplo/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida/tendências , Talidomida/efeitos adversos
7.
Biomed Opt Express ; 3(11): 2937-49, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23162730

RESUMO

Current detection and identification of micro-organisms is based on either rather unspecific rapid microscopy or on more accurate but complex and time-consuming procedures. In a medical context, the determination of the bacteria Gram type is of significant interest. The diagnostic of microbial infection often requires the identification of the microbiological agent responsible for the infection, or at least the identification of its family (Gram type), in a matter of minutes. In this work, we propose to use terahertz frequency range antennas for the enhanced selective detection of bacteria types. Several microorganisms are investigated by terahertz time-domain spectroscopy: a fast, contactless and damage-free investigation method to gain information on the presence and the nature of the microorganisms. We demonstrate that plasmonic antennas enhance the detection sensitivity for bacterial layers and allow the selective recognition of the Gram type of the bacteria.

8.
J Clin Oncol ; 30(24): 2946-55, 2012 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-22802322

RESUMO

PURPOSE: We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM). PATIENTS AND METHODS: In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stem-cell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg/m(2) (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage. RESULTS: Complete response (CR), including near CR, was superior after PAD induction (15% v 31%; P < .001) and bortezomib maintenance (34% v 49%; P < .001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [HR], 0.75; 95% CI, 0.62 to 0.90; P = .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P = .049). In high-risk patients presenting with increased creatinine more than 2 mg/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P = .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P < .001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P = .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P = .003). CONCLUSION: Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS.


Assuntos
Ácidos Borônicos/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Pirazinas/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Talidomida/administração & dosagem , Vincristina/uso terapêutico
9.
Blood ; 118(5): 1239-47, 2011 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-21670471

RESUMO

The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio = 0.83; 95% confidence interval 0.73-0.94, P = .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio = 0.68, 95% confidence interval 0.61-0.76, P < .0001) and better 1-year response rates (partial response or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS and PFS in previously untreated elderly patients with multiple myeloma, extending the median survival time by on average 20%.


Assuntos
Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/uso terapêutico , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Terapia Neoadjuvante , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Talidomida/administração & dosagem , Talidomida/efeitos adversos
10.
ACS Nano ; 5(6): 5151-7, 2011 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-21574624

RESUMO

We demonstrate an improvement by more than 1 order of magnitude of the figure of merit (FoM) of plasmonic nanoparticle sensors by means of the diffractive coupling of localized surface plasmon resonances. The coupling in arrays of nanoparticles leads to Fano resonances with narrow line widths known as surface lattice resonances, which are very suitable for the sensitive detection of small changes in the refractive index of the surroundings. We focus on the sensitivity to the bulk refractive index and find that the sensor FoM scales solely with the frequency difference between the surface lattice resonance and the diffracted order grazing to the surface of the array. This result, which can be extended to other systems with coupled resonances, enables the design of plasmonic sensors with a high FoM over broad spectral ranges with unprecedented accuracy.


Assuntos
Técnicas Biossensoriais/métodos , Nanotecnologia/métodos , Campos Eletromagnéticos , Ouro/química , Teste de Materiais , Nanopartículas Metálicas/química , Microscopia Eletrônica de Varredura/métodos , Modelos Estatísticos , Nanoestruturas , Óptica e Fotônica/métodos , Oscilometria/métodos , Refratometria , Ressonância de Plasmônio de Superfície , Propriedades de Superfície
11.
N Engl J Med ; 364(11): 1027-36, 2011 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-21410371

RESUMO

BACKGROUND: Cytarabine (ara-C) is an important drug in the treatment of acute myeloid leukemia (AML). High-dose cytarabine (2000 to 3000 mg per square meter of body-surface area) is toxic but results in higher rates of relapse-free survival than does the conventional dose of 100 to 400 mg per square meter. Intermediate dose levels have not been thoroughly evaluated. METHODS: We compared two induction regimens in patients 18 to 60 years of age (median, 49) who had newly diagnosed AML. The intermediate-dose group, totaling 431 patients, received cytarabine at a dose of 200 mg per square meter given by continuous intravenous infusion for 24 hours during cycle 1 of induction therapy and 1000 mg per square meter by infusion for 3 hours twice daily during cycle 2 of induction therapy. The high-dose group, totaling 429 patients, received a dose-escalated regimen of 1000 mg of cytarabine per square meter every 12 hours in cycle 1 and 2000 mg per square meter twice daily in cycle 2. Patients with a complete response did not receive additional cytarabine but received consolidation therapy in a third cycle of chemotherapy (mitoxantrone-etoposide) or underwent autologous or allogeneic stem-cell transplantation. Complete remission rates, survival rates, and toxic effects were assessed for each treatment group. RESULTS: At a median follow-up of 5 years, no significant differences were noted between the intermediate-dose group and the high-dose group with respect to complete remission rates (80% and 82%, respectively), probability of relapse, event-free survival at 5 years (34% and 35%), or overall survival (40% and 42%). High-dose cytarabine provided no clear advantage in any prognostic subgroup. The high-dose treatment resulted in higher incidences of grade 3 and grade 4 toxic effects (in cycle 1), prolonged hospitalization, and delayed neutrophil recovery (in cycle 2) and platelet recovery (in cycles 2 and 3). CONCLUSIONS: Induction therapy with cytarabine at the lower dose already produced maximal antileukemic effects for all response end points, suggesting a plateau in the dose-response relationship above this dose level. High-dose cytarabine results in excessive toxic effects without therapeutic benefit. (Netherlands Trial Register number, NTR230.).


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Antimetabólitos Antineoplásicos/efeitos adversos , Terapia Combinada , Citarabina/efeitos adversos , Feminino , Humanos , Análise de Intenção de Tratamento , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão , Transplante de Células-Tronco , Análise de Sobrevida , Adulto Jovem
12.
J Clin Oncol ; 28(19): 3160-6, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20516439

RESUMO

PURPOSE: For several decades, the treatment of elderly patients with multiple myeloma (MM) has consisted of melphalan and prednisone (MP). The Dutch-Belgium Hemato-Oncology Cooperative Group (HOVON) investigated the efficacy of thalidomide added to MP (MP-T) in a randomized phase III trial. The objective of this study was to investigate the efficacy, toxicity, and effects on quality of life of MP-T. PATIENTS AND METHODS: A randomized phase III trial compared standard MP with MP-T (thalidomide 200 mg/d) in newly diagnosed patients with multiple myeloma older than age 65 years. Maintenance therapy with thalidomide 50 mg/d was administered to patients after MP-T until relapse. The primary end point was event-free survival (EFS); response rate, overall survival (OS), and progression-free survival (PFS) were secondary end points. RESULTS: An intent-to-treat analysis of 333 evaluable patients showed significantly higher response rates in MP-T-treated patients compared with MP-treated patients a response (> or = partial response: 66% v 45%, respectively; P < .001; and > or = very good partial response [VGPR]: 27% v 10%, respectively; P < .001). EFS was 13 months with MP-T versus 9 months with MP (P < .001). OS was 40 months with MP-T versus 31 months with MP (P = .05). CONCLUSION: This study demonstrates that thalidomide improves the response rate and VGPR in elderly patients with newly diagnosed MM. MP-T also results in a better EFS, PFS, and OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melfalan/administração & dosagem , Mieloma Múltiplo/patologia , Análise Multivariada , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Dor/induzido quimicamente , Prednisona/administração & dosagem , Qualidade de Vida , Análise de Regressão , Talidomida/administração & dosagem , Resultado do Tratamento
13.
Clin Lymphoma Myeloma Leuk ; 10(2): 138-43, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20371448

RESUMO

BACKGROUND AND METHODS: To obtain efficacy and safety data on lenalidomide treatment outside of clinical trials, we analyzed the clinical data of 114 patients with refractory or relapsed multiple myeloma treated with lenalidomide on a compassionate use basis. The recommended treatment consisted of lenalidomide 25 mg given on days 1-21 of a 28-day cycle, in combination with dexamethasone. A median of 3 previous lines of therapy were given, including thalidomide in 91%. Most patients were treated until progression or intolerable toxicity. RESULTS: The median number of cycles was 7 (range, 1-21+ cycles) with a maximum response after a median of 3 cycles (range, 1-10 cycles). The overall response rate was 69%, including complete response in 6%, very good partial response in 19%, and partial response in 44%. The response rate was not influenced by previous thalidomide and/or bortezomib treatment. The median time to progression (TTP) was 9 months and the median overall survival (OS) was 22 months. A significantly longer TTP was observed in patients who previously underwent allogeneic stem cell transplantation (12.5 months vs. 8 months; P = .036). Overall survival was significantly affected by performance status (P < .0001). Lenalidomide toxicity was predominantly hematologic (37%; Common Toxicity Criteria > or = 3) and the incidence of venous thrombotic events was low (5%) using the recommended prophylaxis. CONCLUSION: This analysis confirms that, outside clinical prospective trials, treatment with lenalidomide is highly effective and feasible in heavily pretreated patients with multiple myeloma.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Talidomida/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácidos Borônicos , Bortezomib , Ensaios Clínicos como Assunto , Ensaios de Uso Compassivo , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Progressão da Doença , Feminino , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/mortalidade , Pirazinas , Recidiva , Pesquisa , Transplante de Células-Tronco , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/análogos & derivados
14.
Blood ; 113(6): 1375-82, 2009 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-18988865

RESUMO

While commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a sibling donor versus no-donor comparison. Eligible patients (433) were entered in 2 consecutive, prospective studies, of whom 288 (67%) were younger than 55 years, in CR1, and eligible to receive consolidation by either an autologous SCT or an allo-SCT. Allo-SCT was performed in 91 of 96 patients with a compatible sibling donor. Cumulative incidences of relapse at 5 years were, respectively, 24 and 55% for patients with a donor versus those without a donor (hazard ratio [HR], 0.37; 0.23-0.60; P < .001). Nonrelapse mortality estimated 16% (+/- 4) at 5 years after allo-SCT. As a result, disease-free survival (DFS) at 5 years was significantly better in the donor group: 60 versus 42% in the no-donor group (HR: 0.60; 0.41-0.89; P = .01). After risk-group analysis, improved outcome was more pronounced in standard-risk patients with a donor, who experienced an overall survival of 69% at 5 years (P = .05). In conclusion, standard-risk ALL patients with a sibling donor may show favorable survival following SCT, due to both a strong reduction of relapse and a modest nonrelapse mortality. This trial is registered with http://www.trialregister.nl under trial ID NTR228.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante Autólogo/métodos , Transplante Homólogo/métodos , Adolescente , Adulto , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Estudos Prospectivos , Indução de Remissão , Fatores de Risco , Irmãos , Condicionamento Pré-Transplante , Resultado do Tratamento , Adulto Jovem
15.
Haematologica ; 92(7): 928-35, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17606443

RESUMO

BACKGROUND AND OBJECTIVES: The Dutch-Belgian HOVON group performed a randomized phase 3 trial to compare single non-myeloablative intensive treatment with double, intensive treatment in previously untreated patients with multiple myeloma (MM). DESIGN AND METHODS: Three hundred and three patients with stage II/III MM were randomized after VAD induction chemotherapy to receive two cycles of non-myeloablative intermediate-dose melphalan (70 mg/m2) (single treatment) or the same regimen followed by cyclophosphamide 120 mg/kg iv plus total body irradiation (TBI) 9 Gy and autologous stem cell transplantation (double, intensive treatment). In both treatment arms interferon .IIa was given as maintenance until relapse/progression. RESULTS: A significantly higher proportion of patients achieved a complete remission (CR) on protocol treatment with double, intensive therapy (32 % vs 13 %, p<0.001). Double treatment produced better outcome in terms of event-free survival (median 22 vs 21 months, 28% vs 14% at 4 years and 15% vs 7% at 6 years after randomization; logrank p=0.013; univariate HR 0.74, 95% CI, 0.58-0.94), progression-free survival (median 27 vs 24 months, 33% vs 16% at 4 years, and 17% vs 9% at 6 years after randomization; logrank p=0.006; HR=0.71, 95% CI 0.56-0.91), but not overall survival (median 50 vs 55 months, 52% vs 56% at 4 years and 39% vs 36% at 6 years after randomization; logrank p=0.51; HR=1.10, 95% CI 0.83-1.46). The achievement of a CR had a favorable prognostic impact on event-free survival (HR=0.60 , 95% CI=0.44 -0.82 , p=0.001) and progression-free survival (HR=0.62 , 95% CI=0.45 -0.84, p=0.002). INTERPRETATION AND CONCLUSIONS: Double, intensive treatment resulted in a better CR rate, event-free survival and progression-free survival but not overall survival compared to single non-myeloablative treatment in previously untreated patients with multiple myeloma.


Assuntos
Melfalan/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Agonistas Mieloablativos/administração & dosagem , Adolescente , Adulto , Idoso , Seguimentos , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Países Baixos , Indução de Remissão , Análise de Sobrevida
16.
Blood ; 101(6): 2144-51, 2003 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-12456509

RESUMO

We compared the efficacy of intensified chemotherapy followed by myeloablative therapy and autologous stem cell rescue with intensified chemotherapy alone in patients newly diagnosed with multiple myeloma. There were 261 eligible patients younger than 66 years with stage II/III multiple myeloma who were randomized after remission induction therapy with vincristine, adriamycin, dexamethasone (VAD) to receive intensified chemotherapy, that is, melphalan 140 mg/m(2) administered intravenously in 2 doses of 70 mg/m(2) (intermediate-dose melphalan [IDM]) without stem cell rescue (n = 129) or the same regimen followed by myeloablative therapy consisting of cyclophosphamide, total body irradiation, and autologous stem cell reinfusion (n = 132). Interferon-alpha-2a was given as maintenance. Of the eligible patients, 79% received both cycles of IDM and 79% of allocated patients actually received myeloablative treatment. The response rate (complete remission [CR] plus partial remission [PR]) was 88% in the intensified chemotherapy group versus 95% in the myeloablative treatment group. CR was significantly higher after myeloablative therapy (13% versus 29%; P =.002). With a median follow-up of 33 months (range, 8-65 months), the event-free survival (EFS) was not different between the treatments (median 21 months versus 22 months; P =.28). Time to progression (TTP) was significantly longer after myeloablative treatment (25 months versus 31 months; P =.04). The overall survival (OS) was not different (50 months versus 47 months; P =.41). Intensified chemotherapy followed by myeloablative therapy as first-line treatment for multiple myeloma resulted in a higher CR and a longer TTP when compared with intensified chemotherapy alone. However, it did not result in a better EFS and OS.


Assuntos
Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Agonistas Mieloablativos/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Causas de Morte , Aberrações Cromossômicas , Terapia Combinada , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Contagem de Leucócitos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Indução de Remissão , Transplante de Células-Tronco , Taxa de Sobrevida , Transplante Autólogo , Vincristina/administração & dosagem , Irradiação Corporal Total
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