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1.
Artigo em Inglês | MEDLINE | ID: mdl-31873987

RESUMO

BACKGROUND: The significance of discrepant findings between histology (BMB) and flow cytometry (FC) in bone marrow (BM) examination at diffuse large B-cell lymphoma (DLBCL) diagnosis is uncertain. METHODS: We performed a 5-year retrospective single-center study of patients diagnosed by DLBCL not otherwise specified (n = 82), divided into three groups according to BM infiltration at diagnosis: BMB-/FC- (75.6%), BMB+/FC+ (13.4%), and BMB-/FC+ (11%). RESULTS: Median infiltration by FC analysis of the BMB-/FC+ group was 0.8% and if we considered BM infiltration as positive in all cases, 4/9 would be upstaged. Median follow was 33 months. Event-free survival (EFS) after 18 months was 82, 23, and 27% for BMB-/FC-, BMB-/FC+, and BMB+/FC+, respectively (p < .001). After 18 months of observation, OS was 87, 46, and 55% for BMB-/FC-, BMB-/FC+, and BMB+/FC+, respectively (p = .001). In multivariate analysis (BM infiltration vs. cell-of-origin according to Hans algorithm and standard IPI), BM infiltration was independently associated with EFS (HR: 1.94, 95% CI: 1.3-2.9) and overall survival (HR: 1.69, 95% CI: 1.1-2.7). CONCLUSION: In summary, minimal BM infiltration, detected by FC but not by BMB, has same prognostic implications than overt BM infiltration and should be considered as extranodal involvement regardless the infiltration quantity.

2.
JAMA ; 322(2): 123-133, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31287523

RESUMO

Importance: Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. Objective: To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. Design, Setting, and Participants: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. Interventions: Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. Main Outcomes and Measures: The primary end point was occurrence of confirmed herpes zoster cases. Results: Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P < .001), equivalent to 68.2% vaccine efficacy. Of 8 secondary end points, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; 95% CI, 0.00-0.78; P = .02) and of other prespecified herpes zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst herpes zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .01). Five secondary objectives were descriptive. Injection site reactions were recorded in 86% of vaccine and 10% of placebo recipients, of which pain was the most common, occurring in 84% of vaccine recipients (grade 3: 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points. Conclusions and Relevance: Among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine compared with placebo significantly reduced the incidence of herpes zoster over a median follow-up of 21 months. Trial Registration: ClinicalTrials.gov Identifier: NCT01610414.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Vacina contra Herpes Zoster , Herpes Zoster/prevenção & controle , Hospedeiro Imunocomprometido , Adjuvantes Imunológicos , Adulto , Feminino , Seguimentos , Herpes Zoster/epidemiologia , Vacina contra Herpes Zoster/administração & dosagem , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/prevenção & controle , Modelos de Riscos Proporcionais , Método Simples-Cego , Transplante Autólogo , Vacinas Sintéticas/administração & dosagem
3.
Am J Hematol ; 94(8): 853-861, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31074033

RESUMO

The value of minimal residual disease (MRD) status by bone marrow and imaging analysis as independent prognostic factors has been well established in multiple myeloma (MM). Nevertheless data about their potential complementarity for a more accurate assessment are limited. With this aim, we retrospectively analyzed the prediction of outcome with the combination of PET-CT and MRD, assessed by multiparameter flow cytometry (MFC) in 103 patients with newly diagnosed MM. We confirmed the benefit in terms of progression-free survival (PFS), linked to the achievement of negativity by MFC (hazard ratio [HR] 0.53; 95% confidence interval [CI]: 0.28-0.98), and PET-CT (HR 0.18; 95% CI: 0.09-0.36) individually. By combining both techniques, patients who became MRD-/PET-, with a median of PFS 92 months, had significant prolonged median PFS (P < .001). This is compared with MRD+/PET- and PET+ patients (median PFS of 45 and 28 months, respectively). We observed a significant difference (P = .003) in overall survival (OS) outcomes between MRD-/PET- and MRD+/PET- patients (4-year OS 94.2% and 100%, respectively), vs PET+ patients (4-year OS 73.8%). All survival results were confirmed in a conditional landmark analysis. These findings support the potential complementarity between PET-CT and MFC, and highlight their better predictive capability when improving sensitivity.

5.
Br J Haematol ; 184(5): 797-807, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30548583

RESUMO

We conducted a phase 2 trial to evaluate the safety and efficacy of bendamustine instead of BCNU (carmustine) in the BEAM (BCNU, etoposide, cytarabine and melphalan) regimen (BendaEAM) as conditioning for autologous stem-cell transplantation (ASCT) in patients with aggressive lymphomas. The primary endpoint was 3-year progression-free survival (PFS). Sixty patients (median age 55 [28-71] years) were included. All patients (except one who died early) engrafted after a median of 11 (9-72) and 14 (4-53) days to achieve neutrophil and platelet counts of >0.5 × 109 /l and >20 × 109 /l, respectively. Non-relapse mortality at 100 days and 1 year were 3.3% and 6.7%, respectively. With a median follow-up of 67 (40-77) months, the estimated 3-year PFS and overall survival (OS) were 58% and 75%, respectively. Patients in partial response at study entry had significantly worse PFS and OS than patients who underwent ASCT in complete metabolic remission, and this was the only prognostic factor associated with both PFS (Relative risk [RR], 0.27 [95% confidence interval {CI} [0.12-0.56]) and OS (RR, 0.40 [95% CI 0.17-0.97]) in the multivariate analysis. BendaEAM conditioning is therefore a feasible and effective regimen in patients with aggressive lymphomas. However, patients not in complete metabolic remission at the time of transplant had poorer survival and so should be considered for alternative treatment strategies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cloridrato de Bendamustina/administração & dosagem , Linfoma/mortalidade , Linfoma/terapia , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Autoenxertos , Cloridrato de Bendamustina/efeitos adversos , Carmustina/administração & dosagem , Carmustina/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Podofilotoxina/administração & dosagem , Podofilotoxina/efeitos adversos , Taxa de Sobrevida
6.
Ann Hematol ; 97(11): 2217-2224, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30019128

RESUMO

Programmed death 1 (PD-1) activation triggers an immune checkpoint resulting in inhibition of T cells that leads to peripheral tolerance. Some PD-1 polymorphisms have been described and associated with the development of autoimmune diseases or cancer predisposition, but there are few data concerning the relevance of such polymorphisms on the clinical outcome after allogeneic hematopoietic stem cell transplant (alloHSCT). We analyzed the distribution of the SNPs PD-1.1G/A (rs36084323) and PD-1.3G/A (rs11568821) genotypes of the donor in a cohort of 1485 alloHSCT from HLA-identical sibling donors. We found an increased risk of grades II to IV graft-versus-host disease (GvHD) in patients receiving grafts from donors homozygous for the G allele at the rs36084323 SNP (P = 0.033; hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.1 to 4.8) and also from donors homozygous for the A allele at the rs11568821 position (P < 0.001; HR 4.5, 95%CI 2.0 to 10.1). In contrast, the PD-1 genotype of the donor did not show association with overall survival or relapse incidence. These results suggest that the PD-1 genotype of the donor plays an important role for the development of acute GvHD after alloHSCT from HLA-identical sibling donors.


Assuntos
Genótipo , Doença Enxerto-Hospedeiro , Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas , Polimorfismo Genético , Receptor de Morte Celular Programada 1/genética , Irmãos , Doença Aguda , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/imunologia , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Taxa de Sobrevida
7.
Cancer Med ; 6(11): 2507-2514, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28960797

RESUMO

Several studies have reported uneven results when evaluating the prognostic value of bone marrow biopsy (BMB) and PET/CT as part of the staging of diffuse large B-cell lymphoma (DLBCL). The heterogeneity of the inclusion criteria and not taking into account selection and collinearity biases in the analysis models might explain part of these discrepancies. To address this issue we have carried a retrospective multicenter study including 268 DLBCL patients with a BMB and a PET/CT available at diagnosis where we estimated both the prognosis impact and the diagnostic accuracy of each technique. Only patients treated with R-CHOP/21 as first line (n = 203) were included in the survival analysis. With a median follow-up of 25 months the estimated 3-year progression-free survival (PFS) and overall survival (OS) were 76.3% and 82.7% respectively. In a multivariate analysis designed to avoid a collinearity bias with IPI categories, BMB-BMI [bone marrow involvement](+) (HR: 3.6) and ECOG PS > 1 (HR: 2.9) were independently associated with a shorter PFS and three factors, age >60 years old (HR: 2.4), ECOG PS >1 (HR: 2.4), and abnormally elevated B2-microglobulin levels (HR: 2.2) were independently associated with a shorter OS. In our DLBCL cohort, treated with a uniform first-line chemotherapy regimen, BMI by BMB complemented performance status in predicting those patients with a higher risk for relapse or progression. In this cohort BMI by PET/CT could not independently predict a shorter PFS and/or OS.


Assuntos
Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Nível de Saúde , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Vincristina/uso terapêutico , Adulto Jovem , Microglobulina beta-2/sangue
8.
Biol Blood Marrow Transplant ; 23(12): 2042-2047, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28827064

RESUMO

Minor histocompatibility antigen (miHA) mismatches have been related to graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, but this association remains controversial due to the lack of consistency in the results obtained by different groups. The CTLA-4 genotype of the donor has been reported to be relevant in the appearance of acute GVHD. We explored the effect of the donor's CTLA-4 genotype in the incidence of acute GVHD associated with HA-1, HA-8, or H-Y miHA mismatches in a large cohort of 1295 patients receiving an allogeneic transplant from an HLA-identical sibling donor. The incidence of acute GVHD was higher if the donor and recipient were mismatched for HA-1, HA-8, or H-Y, but only when the donor had the CTLA-4 rs231775 AA genotype (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.27 to 3.75; P = .005; HR, 2.11, 95% CI, 1.06 to 4.18; P = .033; and HR, 1.50; 95% CI, 1.05 to 2.15; P = .025, respectively). In contrast, this increased risk of developing acute GVHD was not found when the donor presented the CTLA-4 rs231775 AG or GG genotypes. We conclude that the immune response to specific miHA mismatches is modulated by the CTLA-4 genotype of the donor.


Assuntos
Antígeno CTLA-4/genética , Imunidade , Antígenos de Histocompatibilidade Menor/imunologia , Doadores de Tecidos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Genótipo , Doença Enxerto-Hospedeiro/imunologia , Histocompatibilidade/imunologia , Humanos , Lactente , Pessoa de Meia-Idade , Adulto Jovem
9.
Biol Blood Marrow Transplant ; 23(10): 1631-1640, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28533060

RESUMO

High-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) has contributed to modify the natural history of follicular lymphoma (FL); however, an overall survival (OS) benefit has been demonstrated at relapse only after a rituximab-free chemotherapy regimen. A total of 655 patients with FL were reported to the Spanish GELTAMO (Grupo Español de Linfomas y Trasplantes de Médula Ósea) registry and underwent first ASCT between 1989 and 2007. A total of 203 patients underwent ASCT in first complete response (CR1), 174 in second complete response (CR2), 28 in third complete response (CR3), 140 in first partial response (PR1), 81 in subsequent PR, and 29 with resistant/refractory disease; 184 patients received rituximab before ASCT. With a median follow-up of 12 years from ASCT, median progression-free survival (PFS) and overall survival (OS) were 9.7 and 21.3 years, respectively. Actuarial 12-year PFS and OS were 63% (95% confidence interval [CI], 58%-68%) and 73% (95% CI, 68%-78%), respectively, for patients in CR (with a plateau in the curve beyond 15.9 years), 25% (95% CI, 19%-28%) and 49% (95% CI 42%-56%), respectively, for patients in PR, and 23% (95% CI, 8%-48%) and 28% (95% CI, 9%-45%), respectively, for patients with resistant/refractory disease (P < .001). In patients who received rituximab before ASCT, the estimated 9-year PFS and OS from ASCT were 59.5% (95% CI, 51%-67%) and 75% (95% CI, 68%-83%), respectively. Interestingly, for patients who underwent transplantation in CR ≥2 or PR ≥2 who had received rituximab before ASCT (n = 90), 9-year PFS and OS were 61% (95% CI, 51%-73%) and 75% (95% CI, 65%-80%), respectively, with no relapses occurring beyond 5.1 years after ASCT. The cumulative incidence of second malignancies in the global series was 6.7% at 5 years and 12.8% at 10 years. This analysis strongly suggests that ASCT is a potentially curative option for eligible patients with FL. In the setting of relapse, it is of especial interest in pretransplantation rituximab-sensitive patients with FL.


Assuntos
Linfoma Folicular/terapia , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária , Recidiva , Sistema de Registros , Estudos Retrospectivos , Rituximab/uso terapêutico , Transplante Autólogo/métodos , Adulto Jovem
10.
Leuk Lymphoma ; 57(8): 1848-55, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26857688

RESUMO

This phase II study evaluated YM155, a novel small-molecule survivin suppressant, in combination with rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma (NHL) who failed or were not candidates for autologous stem cell transplant (ASCT). During 14-day cycles, 41 patients received YM155 (5mg/m(2)/d) by continuous intravenous (IV) infusion for 168 hours (day 1-7), and rituximab (375mg/m(2)) IV on days 1 and 8 during cycles 1-4 and repeated for 4 cycles every 10 cycles. Forty patients (97.6%) had prior rituximab and 15 patients (36.6%) prior ASCT. Most frequent grade 3-4 adverse events were neutropenia (19.5%) and thrombocytopenia (12.2%). In the per-protocol set (n = 34), objective response rate was 50% and median progression-free survival 17.9 months. Median overall survival was not reached at study termination (median follow-up, 23 months). YM155 in combination with rituximab was tolerable with encouraging antitumor activity and durable responses in relapsed aggressive B-cell NHL patients.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imidazóis/uso terapêutico , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Linfoma de Células B/tratamento farmacológico , Naftoquinonas/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Linfoma de Células B/mortalidade , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Survivina , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Resultado do Tratamento
11.
Rev Esp Quimioter ; 29(1): 15-24, 2016 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-26875567

RESUMO

OBJECTIVE: Infectious complications are an important cause of morbidity and mortality in haematological patients with febrile neutropenia. The aim of this study was to develop a consensus document of recommendations to optimize the management of febrile neutropenic patients with haematological or vascular catheter infections in areas where there is no solid scientific evidence. METHODS: After reviewing the scientific evidence, a scientific committee composed of experts in haematology and infectious diseases developed a survey with 55 statements. A two- round modified Delphi method was used to achieve consensus. RESULTS: The online survey was answered by 52 experts in the field of haematology and infectious diseases. After two rounds of evaluation, a consensus was possible in 43 of the 55 statements (78.2%): 40 in agreement and 3 in disagreement. Recommendations are given related to empirical antibiotic treatment of patients with febrile neutropenia, mechanisms of action, toxicity and synergism of antibiotics in this context, modifications of antibiotic treatment in the course of febrile neutropenia, and the management of central vascular catheter infections in the haematological setting. CONCLUSIONS: There is a high degree of agreement among experts on some controversial issues concerning the management of febrile neutropenia and catheter infection in hematologic patients. This agreement has resulted in recommendations that may be useful in clinical practice.


Assuntos
Bacteriemia/terapia , Infecções Relacionadas a Cateter/terapia , Doenças Hematológicas/complicações , Posicionamento do Paciente , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Bacteriemia/tratamento farmacológico , Infecções Relacionadas a Cateter/tratamento farmacológico , Consenso , Técnica Delfos , Sinergismo Farmacológico , Quimioterapia Combinada , Pesquisas sobre Serviços de Saúde , Doenças Hematológicas/terapia , Humanos , Neutropenia/tratamento farmacológico , Neutropenia/etiologia
12.
Rev. esp. quimioter ; 29(1): 15-24, feb. 2016. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-149283

RESUMO

Introducción. Las complicaciones infecciosas son una causa importante de morbi-mortalidad en los pacientes hematológicos con neutropenia febril. El objetivo del presente trabajo fue desarrollar un documento de recomendaciones consensuado para optimizar el manejo del paciente hematológico con neutropenia febril o infecciones por catéteres vasculares en áreas en las que no se dispone de una sólida evidencia científica. Material y métodos. Tras la revisión de las evidencias científico-médicas, un comité científico formado por especialistas expertos en hematología y enfermedades infecciosas elaboró una encuesta con 55 aseveraciones. Para el consenso se utilizó un método Delphi modificado con dos rondas de evaluación. Resultados. La encuesta fue respondida online por 52 especialistas en hematología y en enfermedades infecciosas. Tras las dos rondas de evaluación fue posible el consenso en 43 de los 55 ítems planteados (un 78,2%): 40 en el acuerdo y 3 en el desacuerdo. Con ello, se proporcionan una serie de recomendaciones relativas al tratamiento antibiótico empírico del paciente con neutropenia febril, a cuestiones relacionadas con mecanismos de acción, toxicidad y sinergia de los antibióticos en este contexto, a las modificaciones del tratamiento antibiótico en el curso de la neutropenia febril y al manejo de las infecciones de catéter vascular central en el ámbito hematológico. Conclusiones. Existe un alto grado de acuerdo entre los expertos consultados sobre algunos aspectos controvertidos relativos al manejo de la neutropenia febril y la infección por catéter en pacientes hematológicos. Este acuerdo se ha traducido en unas recomendaciones que pueden ser de utilidad en la práctica clínica (AU)


Introduction. Infectious complications are an important cause of morbidity and mortality in haematological patients with febrile neutropenia. The aim of this study was to develop a consensus document of recommendations to optimize the management of febrile neutropenic patients with haematological or vascular catheter infections in areas where there is no solid scientific evidence. Materials and Methods. After reviewing the scientific evidence, a scientific committee composed of experts in haematology and infectious diseases developed a survey with 55 statements. A two- round modified Delphi method was used to achieve consensus. Results. The online survey was answered by 52 experts in the field of haematology and infectious diseases. After two rounds of evaluation, a consensus was possible in 43 of the 55 statements (78.2%): 40 in agreement and 3 in disagreement. Recommendations are given related to empirical antibiotic treatment of patients with febrile neutropenia, mechanisms of action, toxicity and synergism of antibiotics in this context, modifications of antibiotic treatment in the course of febrile neutropenia, and the management of central vascular catheter infections in the haematological setting. Conclusions. There is a high degree of agreement among experts on some controversial issues concerning the management of febrile neutropenia and catheter infection in hematologic patients. This agreement has resulted in recommendations that may be useful in clinical practice (AU)


Assuntos
Humanos , Masculino , Feminino , Bacteriemia/complicações , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Infecções Relacionadas a Cateter/complicações , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/epidemiologia , Antibacterianos/uso terapêutico , Conferências de Consenso como Assunto , Inquéritos e Questionários , Coleta de Dados/métodos , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/epidemiologia , Hematologia , Hematologia/estatística & dados numéricos
13.
Clin Infect Dis ; 60(3): 405-14, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25336623

RESUMO

BACKGROUND: The benefit of the combination of serum galactomannan (GM) assay and polymerase chain reaction (PCR)-based detection of serum Aspergillus DNA for the early diagnosis and therapy of invasive aspergillosis (IA) in high-risk hematological patients remains unclear. METHODS: We performed an open-label, controlled, parallel-group randomized trial in 13 Spanish centers. Adult patients with acute myeloid leukemia and myelodysplastic syndrome on induction therapy or allogeneic hematopoietic stem cell transplant recipients were randomized (1:1 ratio) to 1 of 2 arms: "GM-PCR group" (the results of serial serum GM and PCR assays were provided to treating physicians) and "GM group" (only the results of serum GM were informed). Positivity in either assay prompted thoracic computed tomography scan and initiation of antifungal therapy. No antimold prophylaxis was permitted. RESULTS: Overall, 219 patients underwent randomization (105 in the GM-PCR group and 114 in the GM group). The cumulative incidence of "proven" or "probable" IA (primary study outcome) was lower in the GM-PCR group (4.2% vs 13.1%; odds ratio, 0.29 [95% confidence interval, .09-.91]). The median interval from the start of monitoring to the diagnosis of IA was lower in the GM-PCR group (13 vs 20 days; P = .022), as well as the use of empirical antifungal therapy (16.7% vs 29.0%; P = .038). Patients in the GM-PCR group had higher proven or probable IA-free survival (P = .027). CONCLUSIONS: A combined monitoring strategy based on serum GM and Aspergillus DNA was associated with an earlier diagnosis and a lower incidence of IA in high-risk hematological patients. Clinical Trials Registration. NCT01742026.


Assuntos
Aspergilose/diagnóstico , Leucemia Mieloide Aguda/complicações , Mananas/sangue , Síndromes Mielodisplásicas/complicações , Reação em Cadeia da Polimerase em Tempo Real , Adulto , Idoso , Aspergilose/etiologia , Aspergilose/genética , Aspergilose/terapia , Aspergillus/genética , DNA Fúngico/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Secundária
14.
Antimicrob Agents Chemother ; 58(10): 5758-65, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25049247

RESUMO

Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.).


Assuntos
Antifúngicos/uso terapêutico , Micoses/prevenção & controle , Neutropenia/microbiologia , Triazóis/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antifúngicos/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Comprimidos/administração & dosagem , Comprimidos/efeitos adversos , Comprimidos/farmacocinética , Comprimidos/uso terapêutico , Triazóis/administração & dosagem , Triazóis/farmacocinética
15.
Med. clín (Ed. impr.) ; 141(4): e1-e8, ago. 2013.
Artigo em Espanhol | IBECS | ID: ibc-114421

RESUMO

La leucemia linfocítica crónica es el síndrome linfoproliferativo crónico más frecuente en nuestro país, existiendo una amplia heterogeneidad en su abordaje clínico. En la actualidad, en España no se dispone de guías de consenso nacionales similares a las publicadas en otros países para su diagnóstico, clasificación pronóstica y tratamiento. El presente trabajo revisa la evidencia científica actual y aborda cuestiones relacionadas con el diagnóstico, el estudio de extensión, la presencia de comorbilidades y la clasificación de escalas pronósticas, los esquemas de tratamiento habituales estratificados por grupos de riesgo, el tratamiento de las complicaciones asociadas tanto a la enfermedad como a los procedimientos, así como diferentes controversias que rodean a la enfermedad y su tratamiento. El documento, realizado con la colaboración de expertos nacionales, permite establecer unas recomendaciones de carácter práctico, con su correspondiente nivel de evidencia y grado de recomendación, que facilitarán el diagnóstico, tratamiento y seguimiento de los pacientes con leucemia linfocítica crónica (AU)


Chronic lymphocytic leukemia is the most common chronic lymphoproliferative disorder in Spain. The clinical management of this entity varies widely. Currently, in Spain, there are no national consensus guidelines, such as those published in other countries, to guide the diagnosis and treatment of this malignancy and the use of prognostic scores. This article reviews the current scientific literature and addresses issues on the diagnosis of chronic lymphocytic leukemia, the spread of the disease, the presence of comorbidities, the classification of prognostic scores, the common treatment regimens stratified by risk factors, and the management of complications associated with both the disease and its treatment, as well as the various controversies related to this entity. This document was drafted with the collaboration of national experts and aims to establish practical guidelines with their corresponding levels of evidence and grades of recommendation to guide the diagnosis, treatment and follow-up of patients with chronic lymphocytic leukemia (AU)


Assuntos
Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/tratamento farmacológico , Clorambucila/uso terapêutico , Anticorpos Monoclonais/uso terapêutico
16.
Med Clin (Barc) ; 141(4): 175.e1-8, 2013 Aug 17.
Artigo em Espanhol | MEDLINE | ID: mdl-23830547

RESUMO

Chronic lymphocytic leukemia is the most common chronic lymphoproliferative disorder in Spain. The clinical management of this entity varies widely. Currently, in Spain, there are no national consensus guidelines, such as those published in other countries, to guide the diagnosis and treatment of this malignancy and the use of prognostic scores. This article reviews the current scientific literature and addresses issues on the diagnosis of chronic lymphocytic leukemia, the spread of the disease, the presence of comorbidities, the classification of prognostic scores, the common treatment regimens stratified by risk factors, and the management of complications associated with both the disease and its treatment, as well as the various controversies related to this entity. This document was drafted with the collaboration of national experts and aims to establish practical guidelines with their corresponding levels of evidence and grades of recommendation to guide the diagnosis, treatment and follow-up of patients with chronic lymphocytic leukemia.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gerenciamento Clínico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Transfusão de Sangue , Terapia Combinada , Comorbidade , Medicina Baseada em Evidências , Doenças Hematológicas/etiologia , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Hospedeiro Imunocomprometido , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/cirurgia , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/etiologia , Infecções Oportunistas/prevenção & controle , Prognóstico , Recidiva , Fatores de Risco , Terapia de Salvação , Vacinação
17.
Rev Esp Quimioter ; 26(1): 64-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23546466

RESUMO

There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC classification. Most had suspected or proven invasive aspergillosis. We compared patients with prior exposure to mold-active azoles (n=100) to those having not (n=82). The group with prior mold-active azoles included more patients with poor risk features for IFI as acute myeloid leukemia (p<0.05) and prolonged neutropenia (p<0.05). A favorable response in the IFI, defined as a complete or partial response, was achieved in 75% and 74.4% of patients in the whole cohort, and in 66% and 74.4% of patients with probable or proven IFI in the two groups. None of these differences were significant. Multivariate analysis showed that refractory baseline disease and renal dysfunction were adverse factors for response in the IFI (p<0.05). Survival was poorer for patients with prior broad spectrum azoles (p<0.05), and for those who did not recover from neutropenia (p<0.05). In conclusion, the effectiveness of treatment of breakthrough fungal infection with L-AmB is not likely to be affected by prior exposure to mold-active azoles prophylaxis, but survival largely depends on host and disease factors.


Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Fungemia/tratamento farmacológico , Neoplasias Hematológicas/complicações , Triazóis/uso terapêutico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Aspergilose/tratamento farmacológico , Aspergilose/etiologia , Candidíase Invasiva/tratamento farmacológico , Candidíase Invasiva/etiologia , Criança , Pré-Escolar , Terapia Combinada , Infecção Hospitalar/tratamento farmacológico , Avaliação de Medicamentos , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/cirurgia , Transplante de Células-Tronco Hematopoéticas , Humanos , Hospedeiro Imunocomprometido , Lactente , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/cirurgia , Neutropenia/induzido quimicamente , Neutropenia/complicações , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/microbiologia , Estudos Retrospectivos , Risco , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
18.
Rev. esp. quimioter ; 26(1): 64-69, mar. 2013.
Artigo em Inglês | IBECS | ID: ibc-110778

RESUMO

Existe cierta inquietud sobre una reducción del efecto de la anfotericina B liposomal (L-AmB) administrada secuencialmente después de la administración de azoles activos frente a mohos debido a un posible antagonismo en su mecanismo antifúngico. Para investigar este posible efecto en la práctica clínica, hemos estudiado retrospectivamente 182 pacientes hematológicos con infecciones fúngicas invasivas (IFI) de alto riesgo que fueron tratados con L- AmB. En total, 96 pacientes (52,7%) tenían IFI posible, 52 (28,6%) probable y 34 (18,7%) probada de acuerdo con la clasificación de la EORTC. La mayoría presentaban aspergilosis invasiva. Comparamos los pacientes con exposición previa a azoles activos frente a mohos (n=100) con aquellos no expuestos (n=82). El grupo con exposición previa a azoles activos frente a mohos incluía más pacientes con características de alto riesgo de IFI, como leucemia mieloide aguda (p<0,05) y neutropenia prolongada (p<0,05). Se alcanzó una respuesta favorable en la IFI, definida como una respuesta completa o parcial, en 75,0% y 74,4% de los pacientes de la cohorte completa y en 66,0% y 74,4% de los pacientes con IFI probable o probada en los dos grupos. Ninguna de estas diferencias fue significativa. El análisis multivariante mostró que la enfermedad basal y la disfunción renal eran factores adversos para la respuesta en la IFI (p<0,05). La supervivencia fue peor en los pacientes tratados con azoles de amplio espectro (p<0,05) y en aquellos en los que no se resolvió la neutropenia (p<0,05). En conclusión, la eficacia del tratamiento con LAmB de una infección fúngica de brecha probablemente no se vea afectada por la exposición previa a un tratamiento profiláctico con azoles activos frente a mohos, dependiendo la supervivencia más bien de los factores del huésped y de la enfermedad de base(AU)


There are concerns of a reduced effect of liposomal amphotericin B (L-AmB) given sequentially after mold-active azoles due to a possible antagonism in their antifungal mechanism. To investigate this possible effect in the clinic, we retrospectively studied 182 high risk hematologic patients with invasive fungal infections (IFI) who were treated with L-AmB. Overall, 96 patients (52.7%) had possible, 52 (28.6%) probable and 34 (18.7%) proven IFI according to EORTC classification. Most had suspected or proven invasive aspergillosis. We compared patients with prior exposure to mold-active azoles (n=100) to those having not (n=82). The group with prior mold-active azoles included more patients with poor risk features for IFI as acute myeloid leukemia (p<0.05) and prolonged neutropenia (p<0.05). A favorable response in the IFI, defined as a complete or partial response, was achieved in 75% and 74.4% of patients in the whole cohort, and in 66% and 74.4% of patients with probable or proven IFI in the two groups. None of these differences were significant. Multivariate analysis showed that refractory baseline disease and renal dysfunction were adverse factors for response in the IFI (p<0.05). Survival was poorer for patients with prior broad spectrum azoles (p<0.05), and for those who did not recover from neutropenia (p<0.05). In conclusion, the effectiveness of treatment of breakthrough fungal infection with L-AmB is not likely to be affected by prior exposure to mold-active azoles prophylaxis, but survival largely depends on host and disease factors(AU)


Assuntos
Humanos , Masculino , Feminino , Azóis/análise , Azóis/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Doenças Hematológicas/complicações , Doenças Hematológicas/tratamento farmacológico , Anfotericina B/uso terapêutico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Transplante Homólogo/métodos , Transplante Homólogo/tendências , Anfotericina B/análise , Anfotericina B/farmacologia , Fungos , Fungos/metabolismo , Aspergilose/tratamento farmacológico , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/tratamento farmacológico
19.
Blood ; 120(8): 1589-96, 2012 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-22791289

RESUMO

The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone (VTD) versus thalidomide/dexamethasone (TD) versus vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone/bortezomib (VBMCP/VBAD/B) in patients aged 65 years or younger with multiple myeloma. The primary endpoint was complete response (CR) rate postinduction and post-autologous stem cell transplantation (ASCT). Three hundred eighty-six patients were allocated to VTD (130), TD (127), or VBMCP/VBAD/B (129). The CR rate was significantly higher with VTD than with TD (35% vs 14%, P = .001) or with VBMCP/VBAD/B (35% vs 21%, P = .01). The median progression-free survival (PFS) was significantly longer with VTD (56.2 vs 28.2 vs 35.5 months, P = .01). In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs 24%, P = .004) or with VBMCP/VBAD/B (46% vs 38%, P = .1). Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher pre- and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics. Our results support the use of VTD as a highly effective induction regimen prior to ASCT. The study was registered with http://www.clinicaltrials.gov (NCT00461747) and Eudra CT (no. 2005-001110-41).


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/uso terapêutico , Dexametasona/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Pirazinas/uso terapêutico , Talidomida/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/toxicidade , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/efeitos adversos , Ácidos Borônicos/toxicidade , Bortezomib , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/toxicidade , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Pirazinas/toxicidade , Células-Tronco/efeitos dos fármacos , Células-Tronco/patologia , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/toxicidade , Transplante Autólogo
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