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1.
Trials ; 22(1): 595, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488845

RESUMO

BACKGROUND: Chronic lower limb ischemia develops earlier and more frequently in patients with type 2 diabetes mellitus. Diabetes remains the main cause of lower-extremity non-traumatic amputations. Current medical treatment, based on antiplatelet therapy and statins, has demonstrated deficient improvement of the disease. In recent years, research has shown that it is possible to improve tissue perfusion through therapeutic angiogenesis. Both in animal models and humans, it has been shown that cell therapy can induce therapeutic angiogenesis, making mesenchymal stromal cell-based therapy one of the most promising therapeutic alternatives. The aim of this study is to evaluate the feasibility, safety, and efficacy of cell therapy based on mesenchymal stromal cells derived from adipose tissue intramuscular administration to patients with type 2 diabetes mellitus with critical limb ischemia and without possibility of revascularization. METHODS: A multicenter, randomized double-blind, placebo-controlled trial has been designed. Ninety eligible patients will be randomly assigned at a ratio 1:1:1 to one of the following: control group (n = 30), low-cell dose treatment group (n = 30), and high-cell dose treatment group (n = 30). Treatment will be administered in a single-dose way and patients will be followed for 12 months. Primary outcome (safety) will be evaluated by measuring the rate of adverse events within the study period. Secondary outcomes (efficacy) will be measured by assessing clinical, analytical, and imaging-test parameters. Tertiary outcome (quality of life) will be evaluated with SF-12 and VascuQol-6 scales. DISCUSSION: Chronic lower limb ischemia has limited therapeutic options and constitutes a public health problem in both developed and underdeveloped countries. Given that the current treatment is not established in daily clinical practice, it is essential to provide evidence-based data that allow taking a step forward in its clinical development. Also, the multidisciplinary coordination exercise needed to develop this clinical trial protocol will undoubtfully be useful to conduct academic clinical trials in the field of cell therapy in the near future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04466007 . Registered on January 07, 2020. All items from the World Health Organization Trial Registration Data Set are included within the body of the protocol.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Noma , Tecido Adiposo , Animais , Ensaios Clínicos Fase II como Assunto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Método Duplo-Cego , Humanos , Isquemia/diagnóstico , Isquemia/terapia , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Resultado do Tratamento
2.
Leuk Lymphoma ; : 1-8, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34459702

RESUMO

This is a randomized phase-2 trial aimed to compare consolidation vs. maintenance in untreated patients with follicular lymphoma (FL) responding to induction. 146 patients were enrolled from 25 Spanish institutions (ZAR2007; ClinicalTrials.gov #NCT00662948). Patients in PR or CR/CR[u] after R-CHOP were randomized 1:1 to 90Y-ibritumomab-tiuxetan 0.4 mCi/kg (arm A) vs. rituximab 375 mg/m2 every 8 weeks for 2 years (arm B). After a median follow-up of 10.55 years, 53 patients eventually progressed with a 10-year PFS of 50% vs. 56% for patients in arm A and B, respectively (HR = 1.42; p > 0.1). No significant differences were seen in OS (10-year OS 78% vs. 84.5%; HR = 1.39, p > .1). Patients receiving 90Y-ibritumomab-tiuxetan showed higher incidence of second neoplasms than those in arm B (10-year cumulative incidence 18.5 vs. 2%, respectively; p = .038). In conclusion, in FL patients responding to R-CHOP, no significant differences were found between consolidation and maintenance, although with higher late toxicity for consolidation.

3.
Cancer Med ; 10(4): 1314-1326, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33492774

RESUMO

The use of non-pegylated liposomal doxorubicin (Myocet® ) in diffuse large B-cell lymphoma (DLBCL) has been investigated in retrospective and single-arm prospective studies. This was a prospective phase 2 trial of DLBCL patients ≥60 years old with left ventricular ejection fraction (LVEF) ≥55% randomized to standard R-CHOP or investigational R-COMP (with Myocet® instead of conventional doxorubicin). The primary end point was to evaluate the differences in subclinical cardiotoxicity, defined as decrease in LVEF to <55% at the end of treatment. Secondary objectives were efficacy, safety, and variations of troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and LVEF along follow-up. Ninety patients were included, 45 in each group. No differences were observed in the percentage of patients with LVEF <55% at end of treatment (11% in R-CHOP arm vs. 7% in R-COMP arm, p = 0.697) or at 4 months (10% vs. 6%, respectively, p = 0.667) and 12 months (8% vs. 7%, respectively, p = 1). However, a higher percentage of R-CHOP compared with R-COMP patients showed increased troponin levels in cycle 6 (100% vs. 63%, p = 0.001) and at 1 month after treatment (88% vs. 56%, respectively, p = 0.015). Cardiovascular adverse events were seen in five R-CHOP patients (nine episodes, four grade ≥3) and in four R-COMP patients (five episodes, all grade 1-2). No significant differences in efficacy were observed. In conclusion, R-COMP is a feasible immunochemotherapy schedule for DLBCL patients ≥60 years, with similar efficacy to R-CHOP. However, the use of non-pegylated doxorubicin instead of conventional doxorubicin was not associated with less early cardiotoxicity, although some reduced cardiac safety signals were observed. Trial registration: ClinicalTrials.gov Identifier: NCT02012088.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Prospectivos , Estudos Retrospectivos , Rituximab/administração & dosagem , Resultado do Tratamento , Vincristina/administração & dosagem
4.
Blood ; 137(1): 49-60, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-32693406

RESUMO

Patients with multiple myeloma (MM) carrying standard- or high-risk cytogenetic abnormalities (CAs) achieve similar complete response (CR) rates, but the later have inferior progression-free survival (PFS). This questions the legitimacy of CR as a treatment endpoint and represents a biological conundrum regarding the nature of tumor reservoirs that persist after therapy in high-risk MM. We used next-generation flow (NGF) cytometry to evaluate measurable residual disease (MRD) in MM patients with standard- vs high-risk CAs (n = 300 and 90, respectively) enrolled in the PETHEMA/GEM2012MENOS65 trial, and to identify mechanisms that determine MRD resistance in both patient subgroups (n = 40). The 36-month PFS rates were higher than 90% in patients with standard- or high-risk CAs achieving undetectable MRD. Persistent MRD resulted in a median PFS of âˆ¼3 and 2 years in patients with standard- and high-risk CAs, respectively. Further use of NGF to isolate MRD, followed by whole-exome sequencing of paired diagnostic and MRD tumor cells, revealed greater clonal selection in patients with standard-risk CAs, higher genomic instability with acquisition of new mutations in high-risk MM, and no unifying genetic event driving MRD resistance. Conversely, RNA sequencing of diagnostic and MRD tumor cells uncovered the selection of MRD clones with singular transcriptional programs and reactive oxygen species-mediated MRD resistance in high-risk MM. Our study supports undetectable MRD as a treatment endpoint for patients with MM who have high-risk CAs and proposes characterizing MRD clones to understand and overcome MRD resistance. This trial is registered at www.clinicaltrials.gov as #NCT01916252.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Neoplasia Residual/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos de Boro/uso terapêutico , Bortezomib/uso terapêutico , Aberrações Cromossômicas , Dexametasona/uso terapêutico , Feminino , Citometria de Fluxo , Glicina/análogos & derivados , Glicina/uso terapêutico , Humanos , Lenalidomida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Resultado do Tratamento
5.
J Clin Oncol ; 38(8): 784-792, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-31770060

RESUMO

PURPOSE: Assessing measurable residual disease (MRD) has become standard with many tumors, but the clinical meaning of MRD in multiple myeloma (MM) remains uncertain, particularly when assessed by next-generation flow (NGF) cytometry. Thus, we aimed to determine the applicability and sensitivity of the flow MRD-negative criterion defined by the International Myeloma Working Group (IMWG). PATIENTS AND METHODS: In the PETHEMA/GEM2012MENOS65 trial, 458 patients with newly diagnosed MM had longitudinal assessment of MRD after six induction cycles with bortezomib, lenalidomide, and dexamethasone (VRD), autologous transplantation, and two consolidation courses with VRD. MRD was assessed in 1,100 bone marrow samples from 397 patients; the 61 patients without MRD data discontinued treatment during induction and were considered MRD positive for intent-to-treat analysis. The median limit of detection achieved by NGF was 2.9 × 10-6. Patients received maintenance (lenalidomide ± ixazomib) according to the companion PETHEMA/GEM2014MAIN trial. RESULTS: Overall, 205 (45%) of 458 patients had undetectable MRD after consolidation, and only 14 of them (7%) have experienced progression thus far; seven of these 14 displayed extraosseous plasmacytomas at diagnosis and/or relapse. Using time-dependent analysis, patients with undetectable MRD had an 82% reduction in the risk of progression or death (hazard ratio, 0.18; 95% CI, 0.11 to 0.30; P < .001) and an 88% reduction in the risk of death (hazard ratio, 0.12; 95% CI, 0.05 to 0.29; P < .001). Timing of undetectable MRD (after induction v intensification) had no impact on patient survival. Attaining undetectable MRD overcame poor prognostic features at diagnosis, including high-risk cytogenetics. By contrast, patients with Revised International Staging System III status and positive MRD had dismal progression-free and overall survivals (median, 14 and 17 months, respectively). Maintenance increased the rate of undetectable MRD by 17%. CONCLUSION: The IMWG flow MRD-negative response criterion is highly applicable and sensitive to evaluate treatment efficacy in MM.


Assuntos
Citometria de Fluxo/métodos , Mieloma Múltiplo/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Ensaios Clínicos Fase III como Assunto , Dexametasona/administração & dosagem , Feminino , Humanos , Lenalidomida/administração & dosagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Neoplasia Residual/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Am J Hematol ; 94(8): 853-861, 2019 08.
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.


Assuntos
Medula Óssea/patologia , Mieloma Múltiplo/diagnóstico por imagem , Neoplasia Residual/diagnóstico por imagem , Imagem Corporal Total , Medula Óssea/diagnóstico por imagem , Citometria de Fluxo , Humanos , Estimativa de Kaplan-Meier , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Neoplasia Residual/mortalidade , Neoplasia Residual/patologia , Neoplasia Residual/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos
7.
Biol Blood Marrow Transplant ; 25(9): 1703-1712, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31054983

RESUMO

Multiple myeloma (MM) remains as an incurable disease and, although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach, most patients ultimately relapse, and their treatment remains challenging. Because allo-HSCT can modify not only the biology of the disease, but also the immune system and the microenvironment, it can potentially enhance the response to rescue therapies. Information on the efficacy and safety of novel drugs in patients relapsing after allo-HSCT is lacking, however. The objectives of this study were to evaluate the efficacy and toxicity of rescue therapies in patients with MM who relapsed after allo-HSCT, as well as to compare their efficacy before and after allo-HSCT. This retrospective multicenter study included 126 consecutive patients with MM who underwent allo-HSCT between 2000 and 2013 at 8 Spanish centers. All patients engrafted. The incidence of grade II-IV acute graft-versus-host disease (GVHD) was 47%, and nonrelapse mortality within the first 100 days post-transplantation was 13%. After a median follow-up of 92 months, overall survival (OS) was 51% at 2 years and 43% at 5 years. The median progression-free survival after allo-HSCT was 7 months, whereas the median OS after relapse was 33 months. Patients relapsing in the first 6 months after transplantation had a dismal prognosis compared with those who relapsed later (median OS, 11 months versus 120 months; P < .001). The absence of chronic GVHD was associated with reduced OS after relapse (hazard ratio, 3.44; P < .001). Most patients responded to rescue therapies, including proteasome inhibitors (PIs; 62%) and immunomodulatory drugs (IMiDs; 77%), with a good toxicity profile. An in-depth evaluation, including the type and intensity of PI- and IMiD-based combinations used before and after allo-HSCT, showed that the overall response rate and duration of response after allo-HSCT were similar to those seen in the pretransplantation period. Patients with MM who relapse after allo-HSCT should be considered candidates for therapy with new drugs, which can achieve similar response rates with similar durability as seen in the pretransplantation period. This pattern does not follow the usual course of the disease outside the transplantation setting, where response rates and time to progression decreases with each consecutive line of treatment.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Fatores Imunológicos/administração & dosagem , Inibidores de Proteassoma/administração & dosagem , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Recidiva , Estudos Retrospectivos , Espanha/epidemiologia , Taxa de Sobrevida
8.
J Otol ; 14(1): 12-16, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30936896

RESUMO

A rat model of chronic tympanic membrane perforation was developed to be used in the search of new materials for the sealing of these perforations. A longitudinal study was carried out in rats subjected to incisional myringotomy followed by the application of mitomycin C alone or with dexamethasone. Rats were checked at days 3, 7, 10, 14 and weekly thereafter until perforation closure, for up to 6 months. The addition of dexamethasone is a key component in order to obtain a chronic opening. Myringotomies treated with saline had a mean healing time of 8.5 days. At 8 weeks, between 62.5% and 77.7% of tympanic membranes treated with mitomycin C and dexamethasone remained perforated and at 6 months this number fell to 21.4%. This technique is able to maintain most tympanic membrane perforations patent for at least 8 weeks. This rat model is adequate for its use in preclinical or translational research.

11.
Bone Marrow Transplant ; 53(8): 1001-1009, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29463854

RESUMO

The purpose of this retrospective registry study was to investigate the outcome of autoSCT for primary mediastinal B-cell lymphoma (PMBCL) in the rituximab era, including the effects of eventual post-transplant radiotherapy (RT) consolidation. Patients with PMBCL aged between 18 and 70 years who were treated with a first autoSCT between 2000 and 2012 and registered with the EBMT were eligible. Eighty-six patients with confirmed PMBCL and the full data set required for this analysis were evaluable. Sixteen patients underwent autoSCT in remission after first-line therapy (CR/PR1), 44 patients were transplanted with chemosensitive relapsed or primary refractory disease (CR/PR >1), and 24 patients were chemorefractory at the time of autoSCT. With a median follow-up of 5 years, 3-year estimates of relapse incidence, progression-free survival, and overall survival were 6%, 94%, and 100% for CR/PR1; 31%, 64%, and 85% for CR/PR >1; and 52%, 39%, and 41% for REF, respectively. Whilst there was no significant benefit of post-transplant RT in the CR/PR >1 group, RT could completely prevent disease recurrence post d100 in the refractory group. In conclusion, autoSCT with or without consolidating RT is associated with excellent outcome in chemoimmunotherapy-sensitive PMBCL, whereas its benefits seem to be limited in chemoimmunotherapy-refractory disease.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células B/radioterapia , Linfoma de Células B/cirurgia , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Adulto , Idoso , Europa (Continente) , Feminino , Humanos , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
J Vis Exp ; (131)2018 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-29443073

RESUMO

Cell and gene therapy are exciting and promising strategies for the purpose of cardiac regeneration in the setting of heart failure with reduced ejection fraction (HFrEF). Before they can be considered for use, and implemented in humans, extensive preclinical studies are required in large animal models to evaluate the safety, efficacy, and fate of the injectate (e.g., stem cells) once delivered into the myocardium. Small rodent models offer advantages (e.g., cost effectiveness, amenability for genetic manipulation); however, given inherent limitations of these models, the findings in these rarely translate into the clinic. Conversely, large animal models such as rabbits, have advantages (e.g., similar cardiac electrophysiology compared to humans and other large animals), whilst retaining a good cost-effective balance. Here, we demonstrate how to perform a percutaneous contrast echocardiography-guided intramyocardial injection (IMI) technique, which is minimally invasive, safe, well tolerated, and very effective in the targeted delivery of injectates, including cells, into several locations within the myocardium of a rabbit model. For the implementation of this technique, we also have taken advantage of a widely available clinical echocardiography system. After putting in practice the protocol described here, a researcher with basic ultrasound knowledge will become competent in the performance of this versatile and minimally invasive technique for routine use in experiments, aimed at hypothesis testing of the capabilities of cardiac regenerative therapeutics in the rabbit model. Once competency is achieved, the whole procedure can be performed within 25 min after anaesthetizing the rabbit.


Assuntos
Ecocardiografia/métodos , Insuficiência Cardíaca/diagnóstico por imagem , Injeções/métodos , Miocárdio/metabolismo , Animais , Insuficiência Cardíaca/patologia , Humanos , Modelos Animais , Miocárdio/citologia , Coelhos
14.
Am J Hematol ; 93(1): 40-46, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28971503

RESUMO

Whilst autologous stem cell transplantation (auto-SCT) is considered standard of care for relapsed/refractory classical Hodgkin lymphoma, the role of auto-SCT in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is not well defined due to limited data. We report the first study on auto-SCT for NLPHL with a larger cohort. Eligible for this retrospective registry study were patients reported to the EBMT between 2003 and 2013, aged 18 or older with relapsed/refractory NLPHL who underwent first auto-SCT with disease chemosensitive to salvage therapy. NLPHL transformed to diffuse large B cell lymphoma were excluded. Sixty patients (83% male; median age 40 years) met the eligibility criteria. The median time between diagnosis and transplant was 21 months (IQR 13-58), and the median number of prior treatment lines was 2 (range 1-5), including rituximab in 63% of the patients. At auto-SCT, 62% of the patients were in complete remission (CR) and 38% in partial remission. Seventy-two percent of the patients received BEAM as high-dose therapy. With a median follow-up of 56 months (range 3-105), 5-year progression-free and overall survival (OS) were 66% and 87%, respectively. Univariate comparisons considering age, time from diagnosis to transplant, prior chemotherapy lines, and prior rituximab use failed to identify significant predictors for any survival endpoint except for being in CR at the time of auto-SCT (vs PR, P = .049) for OS. Auto-SCT in patients with relapsed/refractory NLPHL who are sensitive to salvage therapy gives excellent disease control and long-term survival independent of the time interval between diagnosis and transplant.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Europa (Continente) , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Cancer Med ; 6(12): 2766-2774, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29076254

RESUMO

Overall survival (OS) is the gold-standard end point for studies evaluating autologous stem cell transplantation (ASCT) in follicular lymphoma (FL), but assessment may be elusive due to the lengthy disease course. We analyzed the validity of two earlier end points, proposed in the setting of first-line chemo-/immunotherapy, as surrogates for OS-progression-free survival (PFS) status at 24 months (PFS24) and complete response at 30 months (CR30) post-ASCT. We also have investigated the clinical features of patients with early progression after ASCT. Data were available for 626 chemosensitive FL patients who received ASCT between 1989 and 2007. Median follow-up was 12.2 years from ASCT. In the PFS24 analysis, 153 (24%) patients progressed within 24 months and 447 were alive and progression-free at 24 months post-ASCT (26 who died without disease progressions within 24 months were excluded). Early progression was associated with shorter OS (hazard ratio [HR], 6.8; P = 0.00001). In the subgroup of patients who received an ASCT in the setting or relapse after being exposed to rituximab, the HR was 11.3 (95% CI, 3.9-30.2; P < 0.00001). In the CR30 analysis, 183 of 596 (31%) response-evaluable patients progressed/died with 30 months post-ASCT. The absence of CR30 was associated with shorter OS (HR, 7.8; P < 0.00001), including in patients with prior rituximab (HR, 8.2). PFS24 and CR30 post-ASCT are associated with poor outcomes and should be primary end points. Further research is needed to identify this population to be offered alternative treatments.


Assuntos
Linfoma Folicular/cirurgia , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Bases de Dados Factuais , Progressão da Doença , Intervalo Livre de Doença , Determinação de Ponto Final , Feminino , Humanos , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Espanha , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
16.
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
17.
J Craniofac Surg ; 28(4): 939-943, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28230598

RESUMO

Among various biomaterials used as scaffolds in tissue engineering, silk fibroin is a highly attractive material. A scaffold should be biocompatible and nontoxic, with optimal physical features and mechanical properties. For this reason, tissue-engineering approaches in regenerative medicine have focused on investigating the biocompatibility of possible biomaterials by analyzing cell-scaffold interaction properties. The aim of the present study was to examine the biocompatibility of silk fibroin as a film (two-dimensional [2D]) and a scaffold (three-dimensional [3D]) after being cellularized with human dental pulp stem cells (hDPSCs). Human dental pulp stem cells were isolated from healthy patients aged between 18 and 31 years. Further, silk fibroin-based 2D films and 3D scaffolds were prepared. Human dental pulp stem cells were directly seeded onto the biomaterial surfaces and their proliferation, adherence, and cell morphology were analyzed after 24, 120, and 168 hours. Additionally, the characteristics of the silk fibroin 2D films and 3D scaffolds before and after cell seeding were analyzed by scanning electron microscopy. After the initial 24 hours, silk fibroin-based 3D scaffolds displayed more adhered cells with a suitable fibroblastic morphology than those displayed on the 2D films. After longer culture times, hDPSCs proliferated sufficiently to cover the entire surface of the 3D silk fibroin scaffold, whereas the 2D films were only partially covered. Our results indicate the good in vitro biocompatibility of silk fibroin-based biomaterials, especially when 3D scaffolds rather than 2D films are used.


Assuntos
Células-Tronco Adultas/fisiologia , Materiais Biocompatíveis , Adesão Celular , Polpa Dentária/citologia , Fibroínas , Engenharia Tecidual/métodos , Tecidos Suporte , Adolescente , Adulto , Células-Tronco Adultas/citologia , Animais , Proliferação de Células , Humanos , Adulto Jovem
18.
Hematol Oncol ; 34(2): 108-114, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25491088

RESUMO

Multiple myeloma (MM) is a hematologic neoplasm characterized by plasma tumor cell proliferation in the bone marrow. It's a rare malignancy before a 40-year-old and it is extremely uncommon during pregnancy. We report the case of a 37-year-old woman with a newly diagnosed IgG λ MM (Durie-Salmon stage IIIA, International Staging System II and good prognosis cytogenetic) at the 27th week of her pregnancy. Our management during pregnancy, the delivery, and initiation of anti-myeloma treatment with bortezomib, lenalidomide, and dexamethasone are published. There are a few reviews reporting the most common features and management of MM during pregnancy. We perform a comprehensive review of all 32 cases reported between 1965 and 2014 in which a MM was diagnosed during pregnancy including score, cytogenetic results, labor characteristics, and response to therapy. About 53% of pregnant women did not start treatment before partum. Cesarean section was the most common form of delivery (82%). About 88% of newborns were healthy, although most of them were premature (73%). Management of a MM diagnosed during pregnancy should be based on the presence of myeloma-related organ damage to secure survival of the mother without fetal adverse effects related to treatment. Serial fetal ultrasound may be helpful in order to avoid complications. The cesarean section may be preferred depending on maternal and fetus prognosis. Whole-body diffusion-weighted imaging minimal response could be an appropriate technique to discard plasmacytomas during pregnancy in critical situations such as the appearance of symptoms of spinal cord compression. Therapeutic choices should be agreed with the pregnant after a thorough discussion of the prognostic factors of the disease and the potential risk for the fetus and the patient. While awaiting partum, dexamethasone is a non-toxic treatment. Triple therapy including a proteasome inhibitor should be started quickly after delivery. Copyright © 2014 John Wiley & Sons, Ltd.

19.
Respir Physiol Neurobiol ; 221: 54-8, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26593639

RESUMO

The safety of autologous bone marrow mononuclear cells (ABMNC) intraspinal infusion in amyotrophic lateral sclerosis (ALS) patients was evaluated considering breathing and sleep patterns. Patients between 20 and 65 years old were eligible if they had definite ALS, spinal onset, a disease duration between 6 and 36 months, FVC>50%, and a below 90% oxygen saturation (T90) <2% of sleep time. The transplant was performed 6 months after enrollment. ABMNC were infused at thoracic 3-4 level. Eleven patients were included. The REM sleep decreased slightly one year after the cell transplant but not significantly. There were no differences in apnea-hipopnea index, mean oxygen saturation and nadir desaturation evolution. An increase of T90 was observed 180 and 360 days after injection (2.95±1.51% and 4.30±4.10% respectively), although it was not statistically significant. The central drive determined by occlusion pressure (P01) and inspiratory flow showed non-significant differences after one year. Intramedullary injection of ABMNC did not worsen the cortico medullar diaphragmatic pathways.


Assuntos
Esclerose Amiotrófica Lateral/complicações , Esclerose Amiotrófica Lateral/cirurgia , Transplante de Medula Óssea/métodos , Pneumopatias/etiologia , Respiração , Adulto , Feminino , Seguimentos , Humanos , Injeções Espinhais , Leucócitos Mononucleares/fisiologia , Leucócitos Mononucleares/transplante , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Polissonografia , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/cirurgia , Espirometria , Resultado do Tratamento
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