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1.
Br J Haematol ; 196(4): 1018-1030, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34750806

RESUMEN

We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58 months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo/métodos , Adulto , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
2.
Ann Oncol ; 30(4): 612-620, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30657848

RESUMEN

BACKGROUND: In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: This was a multicenter, open-label, phase I-II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day ‒1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT. RESULTS: A total of 66 patients were recruited (median age 36 years; range 18-66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3-4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3-4 extrahematological adverse events (≥5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2×10e6/kg CD34+ cells (median 5.75; range 2.12-33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%). CONCLUSION: BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Brentuximab Vedotina/administración & dosificación , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Enfermedad de Hodgkin/terapia , Recurrencia Local de Neoplasia/terapia , Terapia Recuperativa/métodos , Administración Intravenosa , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Brentuximab Vedotina/efectos adversos , Neutropenia Febril Inducida por Quimioterapia/etiología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Citarabina/administración & dosificación , Citarabina/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/efectos adversos , Terapia Neoadyuvante/métodos , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Prednisona/administración & dosificación , Prednisona/efectos adversos , Supervivencia sin Progresión , Terapia Recuperativa/efectos adversos , Trasplante Autólogo , Adulto Joven
4.
Health Qual Life Outcomes ; 17(1): 11, 2019 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-30642340

RESUMEN

BACKGROUND: The purpose of this study is to describe Health-Related Quality of Life (HRQoL) of localized prostate cancer patients in an Active Surveillance (AS) program, and to compare them with those undergoing radical prostatectomy (RP), external-beam radiotherapy (XRT) and brachytherapy (BT). METHODS: Multi-institutional pooled cross-sectional analysis on patients in an AS protocol: < 75 years old; pathologically confirmed LPC (maximum of three positive cylinders); Gleason score < 3 + 4; clinical stage T1a-T2b; and PSA < 15 ng/ml. Exclusion criteria for this study were: less than 6 months in AS, termination of AS protocol, or incomplete data. Patients in AS were matched with those treated with RP, XRT or BT from the 'Spanish Multicentric Study of Clinically Localized Prostate Cancer' cohort according to risk group, time from treatment selection to HRQoL survey, and age. Prostate-specific (EPIC) and generic (SF-36) HRQoL instruments were completed. Analysis was stratified by HRQoL survey moment (>or < 2.5 years from treatment selection), and age (>or < 70 years old). RESULTS: Median of time from treatment selection to HRQoL survey in the total 396 patients (99 per treatment group) was 2.4 years (range 0.5-8.3). Patients in AS presented higher (better) urinary incontinence scores than RP ones in both stratus of time from treatment selection to HRQoL survey (92.6 vs 67.0 and 81.4 vs 64.4, p <  0.01). Patients in AS for < 2.5 years presented greater sexual scores than any active treatment (p <  0.01), but only statistically higher than RP for those in AS for longer than 2.5 years. The magnitude of the differences between AS and RP groups in both EPIC domains ranged from moderate (0.7 SD) to large (1.0 SD). Regardless of treatment applied, patients presented similar and slightly increased SF-36 scores than US general population reference norms. Nonetheless, patients in AS for < 2.5 years reported worse outcomes than other treatment groups on physical health domains, especially in bodily pain (0.5-0.6 SD), and vitality (0.6-0.8 SD). CONCLUSIONS: Considering patients' well-being, AS can be a good therapeutic option due to the low impact caused on urinary continence and sexual function. However, longitudinal studies are required to take into account HRQoL evolution over time.


Asunto(s)
Prostatectomía , Neoplasias de la Próstata/terapia , Calidad de Vida , Espera Vigilante , Anciano , Braquiterapia/efectos adversos , Braquiterapia/estadística & datos numéricos , Estudios de Casos y Controles , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Prostatectomía/efectos adversos , Prostatectomía/estadística & datos numéricos , Neoplasias de la Próstata/psicología , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/estadística & datos numéricos , Espera Vigilante/estadística & datos numéricos
5.
Environ Res ; 159: 135-142, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28800471

RESUMEN

A total of 417 striped red mullet, Mullus surmuletus, were analyzed to study microplastic ingestion and livers of fish were assessed to study effects of microplastics. Nearly one third (27.30%) of the individuals were quantified to ingest microplastics although there was no evidence of oxidative stress or cellular damage in the liver of fish which had ingested microplastics. A small increase in the activity of glutathione S-transferase (GST) of M. surmuletus was detected which could be suggesting an induction of the detoxification systems but these findings should be tested in laboratory conditions under a controlled diet and known concentration of microplastics. Fish from trammel fisheries, operating closer to land and targeting larger individuals, showed higher mean ingestion values than fish from trawling fisheries, and were related to body size, as microplastics ingested increased with total fish length. Consequently, ingestion values of microplastics were not related to sampling distance from land giving further evidence of the ubiquity of microplastics in the marine environment. Finally, Fourier Transform Infrared Spectroscopy (FTIR) analysis showed that the vast majority of microplastics were filament type and polyethylene terephthalate (PET) was the main identified component.


Asunto(s)
Contaminación de Alimentos/análisis , Estrés Oxidativo , Perciformes/metabolismo , Plásticos/metabolismo , Alimentos Marinos/análisis , Contaminantes Químicos del Agua/metabolismo , Animales , Ingestión de Alimentos , Monitoreo del Ambiente , Femenino , Masculino , España
6.
Ann Oncol ; 27(12): 2251-2257, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-28007754

RESUMEN

BACKGROUND: To evaluate long-term outcome of myeloablative allogeneic stem cell transplantation (allo-SCT) (MAC) versus reduced-intensity allo-SCT (RIC) in patients with relapsed/refractory Hodgkin's lymphoma (HL) in recent years. PATIENTS AND METHODS: A total of 312 patients (63 MAC and 249 RIC) with relapsed/refractory HL who received allo-SCT between 2006 and 2010 and were reported to the EBMT Database were included in the study. RESULTS: With a median follow-up for alive patients of 56 (26-73) months, there were no significant differences in non-relapse mortality (NRM) between MAC and RIC. Relapse rate (RR) was somewhat lower in the MAC group (41% versus 52% at 24 months, P = 0.16). This lower RR translated into a marginal improvement in event-free survival (EFS) for the MAC group (48% versus 36% at 24 months, P = 0.09) with no significant differences in overall survival (73% for MAC and 62% for RIC at 24 months, P = 0.13). Multivariate analysis after adjusting for disease status at the time of allo-SCT showed that the use of MAC was of borderline statistical significance for predicting a lower RR and EFS [HR 0.7, 95% CI (0.5-1.0), P = 0.1] and [HR 0.7, 95% CI (0.5-1.0), P = 0.07], respectively, after allo-SCT. CONCLUSIONS: With modern transplant practices, the NRM associated with MAC for HL has strongly decreased, resulting into non-significant improvement of EFS because of a somewhat better disease control compared with RIC transplants. The intensity of conditioning regimens should be considered when designing individual allo-SCT strategies or clinical trials in patients with relapsed/refractory HL.


Asunto(s)
Enfermedad Injerto contra Huésped/epidemiología , Enfermedad de Hodgkin/terapia , Recurrencia Local de Neoplasia/terapia , Trasplante de Células Madre/métodos , Trasplante Homólogo/métodos , Adulto , Anciano , Médula Ósea , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Enfermedad de Hodgkin/patología , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Trasplante de Células Madre/efectos adversos , Acondicionamiento Pretrasplante , Trasplante Homólogo/efectos adversos , Resultado del Tratamiento
7.
J Sports Med Phys Fitness ; 55(4): 345-51, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25369272

RESUMEN

AIM: Changes in IL-6, TNF-α, and TNF-α receptors - sTNFRI and sTNFRII - were evaluated in a group of professional cyclists treated with immunomodulator AM3 (Inmunoferón®) for 6 months of training and competition. METHODS: Sixteen male professional cyclists with a similar training program participated in the study which was designed as a randomized, placebo-controlled, double-blind clinical trial. Venous blood samples were collected in basal conditions, before beginning the supplementation program, and after 90 and 180 days of training and competition season. RESULTS: No significant differences in biochemical parameters or in IL-6 were evidenced between placebo and AM3-treated groups throughout the study. Plasma TNF-α levels significantly decreased (P<0.05) after 90 days of training in the AM3 treated group. TNF-α receptors increased during training season in both placebo and AM3 treated groups, although the increase was significantly higher (P<0.05) in the AM3 group with respect to the placebo group. CONCLUSION: The changes produced by regular training and competition were modified throughout the season by AM3 treatment which could reduce the inflammatory response to excessive exercise.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Atletas , Fosfatos de Calcio/farmacología , Glicopéptidos/farmacología , Interleucina-6/sangre , Receptores del Factor de Necrosis Tumoral/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto , Ciclismo , Método Doble Ciego , Humanos , Masculino , Adulto Joven
8.
Ann Oncol ; 25(11): 2224-2229, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25193988

RESUMEN

BACKGROUND: The aim of this study was to investigate the impact of the high-dose regimen on the outcome of patients with follicular lymphoma (FL) having had autologous stem-cell transplantation (ASCT) in a recent time period. PATIENTS: Between 1995 and 2007, 2233 patients with FL had their first ASCT with either a total body irradiation (TBI)-containing regimen or carmustin, etoposide, cytarabine and melphalan (BEAM), of which 47% were autografted in first remission. RESULTS: After a median observation time of 73 months (interquartile range 30-107), 5- and 10-year non-relapse mortality (NRM) was similar (6% and 10% in both groups). No significant NRM differences became evident after multivariate adjustment for confounders. Secondary malignancies were observed in 9.7% and 7.9% of the patients after TBI and BEAM (P = 0.19), which were treatment-related myelodysplastic syndromes/acute myelogenous leukaemia (t-MDS/AML) in 3.4% and 2.8% (P = 0.57). The median time to t-MDS/AML was around 50 months in both groups. Because of a lower relapse incidence, TBI was associated with better event-free survival reaching statistical significance in the patients transplanted in first remission but not in those transplanted beyond first remission. CONCLUSIONS: In patients with FL who received TBI-based ASCT after 1995 increased NRM and t-MDS/AML risks did not emerge compared with BEAM while disease control was at least equivalent.


Asunto(s)
Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/radioterapia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/radioterapia , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carmustina/administración & dosificación , Carmustina/efectos adversos , Terapia Combinada , Citarabina/administración & dosificación , Citarabina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma Folicular/patología , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Podofilotoxina/administración & dosificación , Podofilotoxina/efectos adversos , Inducción de Remisión , Rituximab , Trasplante de Células Madre , Trasplante Autólogo , Irradiación Corporal Total , Adulto Joven
9.
Cytokine ; 69(2): 155-64, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24954162

RESUMEN

Exercise induces changes in circulating pro- and anti-inflammatory cytokines. The aim was to investigate the effect of docosahexaenoic acid (DHA) diet supplementation on the plasma cytokine levels and on the peripheral mononuclear (PBMCs) cells cytokine production after a training season or an acute bout of exercise. Fifteen male soccer players were randomly assigned to a placebo or an experimental group. The experimental group consumed an almond-based beverage enriched with DHA, whereas the placebo group consumed the same beverage without DHA. Three blood samples were taken: in basal conditions at the beginning of the nutritional intervention and after eight weeks of training season in basal and post-exercise conditions. The DHA content increased in erythrocytes after 8weeks of training and supplementation. Neither diet supplementation with DHA nor training season altered the basal plasma cytokines and growth factors. Only acute exercise significantly increased plasma IL6 in experimental and placebo groups. Lipopolysaccharide (LPS) activation induced the inflammatory response in PBMCs, with a significant production rate of TNFα, IL6 and IL8 mainly after acute exercise. DHA supplementation significantly reduced the rate of TNFα and IL6 production by stimulated PBMCs. Acute exercise increased the Toll-like receptor 4 (TLR4) protein levels in PBMCs, although the increase was only statistically significant in the placebo group. In conclusion, a training season does not induce significant changes in the circulating cytokine profile in well-trained soccer players. Exercise increases the PBMCs cell capabilities to produce cytokines after TLR4 stimulation with LPS and this rate of cytokine production is attenuated by diet DHA supplementation.


Asunto(s)
Suplementos Dietéticos , Ácidos Docosahexaenoicos/farmacología , Ejercicio Físico , Inflamación/patología , Leucocitos Mononucleares/patología , Lipopolisacáridos/farmacología , Bebidas , Recuento de Células , Citocinas/sangre , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intercelular/sangre , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Masculino , Receptor Toll-Like 4/metabolismo , Adulto Joven
10.
Mitochondrion ; 76: 101869, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38467292

RESUMEN

Hydrogen peroxide (H2O2) is a reactive species that is also involved in the redox regulation of cells because of it is relative stability. In numerous pathological situations, a chronic increase in the production of reactive species is observed, which is related to oxidative stress and cellular damage. This study aimed to evaluate the effects of long-term exposure to different H2O2 concentrations on oxidative stress biomarkers and mitochondrial dynamics in HL60 cells. HL60 cells were treated with a sustained production (0.1, 1.0 and 10.0 nM/s) of H2O2 for one hour. H2O2 production and malondialdehyde (MDA) levels, as a lipid peroxidation marker, increased progressively in HL60 cells in accordance with higher H2O2 exposure, with significant differences between the 10 nM/s H2O2 group and the control and 0.1 nM/s groups. Similarly, progressive increased expression in genes related to the mitochondrial antioxidant defences and mitochondrial dynamics were also observed. Significantly increased gene expression in the 10 nM/s H2O2 with respect to the control group was observed for manganese superoxide dismutase (MnSOD), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG1α), nuclear respiratory factor 2 (Nrf2), mitochondrial transcription factor A (Tfam), mitofusins 1 and 2 (Mfn1 and Mfn2) and uncoupling protein 3 (UCP3), whereas no significant changes were observed in the cytochrome c oxidase subunit IV (COXIV) gene expression. In conclusion, exposure to different sustained production of H2O2 is related to a progressive increase in the gene expression of mitochondrial dynamics and redox processes in HL60 cells, but also to oxidative damage at higher H2O2 production levels.


Asunto(s)
Peróxido de Hidrógeno , Peroxidación de Lípido , Mitocondrias , Estrés Oxidativo , Especies Reactivas de Oxígeno , Humanos , Peróxido de Hidrógeno/metabolismo , Estrés Oxidativo/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Células HL-60 , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Malondialdehído/metabolismo
11.
Bone Marrow Transplant ; 59(2): 232-238, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38007531

RESUMEN

Allogeneic haematopoietic cell transplantation (alloHCT) has curative potential counterbalanced by its toxicity. Prognostic scores fail to include current era patients and alternative donors. We examined adult patients from the EBMT registry who underwent alloHCT between 2010 and 2019 for oncohaematological disease. Our primary objective was to develop a new prognostic score for overall mortality (OM), with a secondary objective of predicting non-relapse mortality (NRM) using the OM score. AI techniques were employed. The model for OM was trained, optimized, and validated using 70%, 15%, and 15% of the data set, respectively. The top models, "gradient boosting" for OM (AUC = 0.64) and "elasticnet" for NRM (AUC = 0.62), were selected. The analysis included 33,927 patients. In the final prognostic model, patients with the lowest score had a 2-year OM and NRM of 18 and 13%, respectively, while those with the highest score had a 2-year OM and NRM of 82 and 93%, respectively. The results were consistent in the subset of the haploidentical cohort (n = 4386). Our score effectively stratifies the risk of OM and NRM in the current era but do not significantly improve mortality prediction. Future prognostic scores can benefit from identifying biological or dynamic markers post alloHCT.


Asunto(s)
Inteligencia Artificial , Trasplante de Células Madre Hematopoyéticas , Humanos , Adulto , Trasplante Homólogo , Recurrencia Local de Neoplasia , Trasplante de Células Madre Hematopoyéticas/métodos , Pronóstico , Enfermedad Crónica , Estudios Retrospectivos
12.
Ann Oncol ; 24(9): 2430-4, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23712545

RESUMEN

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. METHODS: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. RESULTS: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. CONCLUSION(S): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.


Asunto(s)
Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/cirugía , Recurrencia Local de Neoplasia/mortalidad , Trasplante de Células Madre , Adolescente , Adulto , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Sobrevida , Trasplante Autólogo , Insuficiencia del Tratamiento , Adulto Joven
13.
Semin Hematol ; 60(5): 305-312, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38342663

RESUMEN

In the era of immunochemotherapy, approximately 60%-70% of diffuse large B-cell lymphoma (DLBCL) patients achieve remission with first-line rituximab-based chemoimmunotherapy. However, 30%-40% relapse after initial response to first-line therapy and, out of them, 20%-50% are refractory or experience early relapse. The second-line therapy algorithm for DLBCL has recently evolved, thanks to the recent approval of new therapeutic agents or their combinations. The new guidelines suggest a stratification of relapsed/refractory (R/R) DLBCL based on the time to relapse. For transplant-eligible patients, autologous stem cell transplant remains the preferred option when the patient relapses after 12 months from diagnosis, while anti-CD19 CART-cell therapy is the current preferred choice for high-risk DLBCL, defined as primary refractory or relapse ≤12 months. For transplant-ineligible or CAR T-cell therapy-ineligible patients, the therapeutic arsenal historically lacked effective options. However, new therapeutic options, including polatuzumab vedotin combined with bendamustine-rituximab and tafasitamab with lenalidomide, have been recently approved, and novel agents such as loncastuximab tesirine, selinexor, anti-CD19 CAR T-cell therapy, and bispecific antibodies have shown promising efficacy and manageable safety in this setting offering new hope to patients in this challenging scenario.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Humanos , Rituximab/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Recurrencia
14.
Transplant Cell Ther ; 29(3): 151-163, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36442770

RESUMEN

Transplantation-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic cell transplantation (HCT) associated with significant morbidity and mortality. However, TA-TMA is a clinical diagnosis, and multiple criteria have been proposed without universal application. Although some patients have a self-resolving disease, others progress to multiorgan failure and/or death. Poor prognostic features also are not uniformly accepted. The lack of harmonization of diagnostic and prognostic markers has precluded multi-institutional studies to better understand incidence and outcomes. Even current interventional trials use different criteria, making it challenging to interpret the data. To address this urgent need, the American Society for Transplantation and Cellular Therapy, Center for International Bone Marrow Transplant Research, Asia-Pacific Blood and Marrow Transplantation, and European Society for Blood and Marrow Transplantation nominated representatives for an expert panel tasked with reaching consensus on diagnostic and prognostic criteria. The panel reviewed literature, generated consensus statements regarding diagnostic and prognostic features of TA-TMA using the Delphi method, and identified future directions of investigation. Consensus was reached on 4 key concepts: (1) TA-TMA can be diagnosed using clinical and laboratory criteria or tissue biopsy of kidney or gastrointestinal tissue; however, biopsy is not required; (2) consensus diagnostic criteria are proposed using the modified Jodele criteria with additional definitions of anemia and thrombocytopenia. TA-TMA is diagnosed when ≥4 of the following 7 features occur twice within 14 days: anemia, defined as failure to achieve transfusion independence despite neutrophil engraftment; hemoglobin decline by ≥1 g/dL or new-onset transfusion dependence; thrombocytopenia, defined as failure to achieve platelet engraftment, higher-than-expected transfusion needs, refractory to platelet transfusions, or ≥50% reduction in baseline platelet count after full platelet engraftment; lactate dehydrogenase (LDH) exceeding the upper limit of normal (ULN); schistocytes; hypertension; soluble C5b-9 (sC5b-9) exceeding the ULN; and proteinuria (≥1 mg/mg random urine protein-to-creatinine ratio [rUPCR]); (3) patients with any of the following features are at increased risk of nonrelapse mortality and should be stratified as high-risk TA-TMA: elevated sC5b-9, LDH ≥2 times the ULN, rUPCR ≥1 mg/mg, multiorgan dysfunction, concurrent grade II-IV acute graft-versus-host disease (GVHD), or infection (bacterial or viral); and (4) all allogeneic and pediatric autologous HCT recipients with neuroblastoma should be screened weekly for TA-TMA during the first 100 days post-HCT. Patients diagnosed with TA-TMA should be risk-stratified, and those with high-risk disease should be offered participation in a clinical trial for TA-TMA-directed therapy if available. We propose that these criteria and risk stratification features be used in data registries, prospective studies, and clinical practice across international settings. This harmonization will facilitate the investigation of TA-TMA across populations diverse in race, ethnicity, age, disease indications, and transplantation characteristics. As these criteria are widely used, we expect continued refinement as necessary. Efforts to identify more specific diagnostic and prognostic biomarkers are a top priority of the field. Finally, an investigation of the impact of TA-TMA-directed treatment, particularly in the setting of concurrent highly morbid complications, such as steroid-refractory GVHD and infection, is critically needed.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Microangiopatías Trombóticas , Humanos , Niño , Pronóstico , Médula Ósea , Estudios Prospectivos , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos
15.
Rev Esp Quimioter ; 36(1): 1-25, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36322133

RESUMEN

We do not know the precise figure for solid organ tumors diagnosed each year in Spain and it is therefore difficult to calculate whether there has been a decrease in cancer diagnoses as a consequence of the pandemic. Some indirect data suggest that the pandemic has worsened the stage at which some non-hematological neoplasms are diagnosed. Despite the lack of robust evidence, oncology patients seem more likely to have a poor outcome when they contract COVID-19. The antibody response to infection in cancer patients will be fundamentally conditioned by the type of neoplasia present, the treatment received and the time of its administration. In patients with hematological malignancies, the incidence of infection is probably similar or lower than in the general population, due to the better protective measures adopted by the patients and their environment. The severity and mortality of COVID-19 in patients with hematologic malignancies is clearly higher than the general population. Since the immune response to vaccination in hematologic patients is generally worse than in comparable populations, alternative methods of prevention must be established in these patients, as well as actions for earlier diagnosis and treatment. Campaigns for the early diagnosis of malignant neoplasms must be urgently resumed, post-COVID manifestations should be monitored, collaboration with patient associations is indisputable and it is urgent to draw the right conclusions to improve our preparedness to fight against possible future catastrophes.


Asunto(s)
COVID-19 , Neoplasias Hematológicas , Humanos , Pandemias/prevención & control , COVID-19/diagnóstico , Neoplasias Hematológicas/complicaciones , España/epidemiología , Vacunación , Prueba de COVID-19
16.
Ann Oncol ; 23(1): 166-171, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21467125

RESUMEN

BACKGROUND: Limited experience is available on the feasibility and efficacy of autologous stem-cell transplantation (ASCT) in patients with mantle cell lymphoma (MCL) beyond 65 years. DESIGN AND METHODS: We analysed 712 patients with MCL treated with ASCT from 2000 to 2007 and reported to the European Group for Blood and Marrow Transplantation registry. Patients>65 years were compared with patients<65 years for the end points non-relapse mortality (NRM), relapse incidence, progression-free survival (PFS), and overall survival (OS). RESULTS: Seventy-nine patients were ≥65 years old. Median time from diagnosis to ASCT was longer in the elderly patients (11 versus 9 months, P=0.005); they had more commonly received at least two treatment lines (62.0% versus 47.9%, P=0.02) and were less commonly in first complete remission at ASCT (35.4% versus 51.2%, P=0.002). Median follow-up after ASCT was 19 and 25 months, respectively. NRM was comparable at 3 months (3.8% versus 2.5%) and at 5 years (5.6% versus 5.0%). There were no differences in relapse rate (66% versus 55% at 5 years), PFS (29% versus 40%) and OS (61% versus 67%) between both populations of patients. CONCLUSION: ASCT beyond 65 years of age is feasible in selected patients with MCL and results in similar disease control and survival as in younger patients.


Asunto(s)
Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/cirugía , Trasplante de Células Madre/mortalidad , Adulto , Distribución por Edad , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Trasplante Autólogo
17.
Br J Nutr ; 107 Suppl 2: S23-52, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22591897

RESUMEN

Omega 3 fatty acids can be obtained from several sources, and should be added to the daily diet to enjoy a good health and to prevent many diseases. Worldwide, general population use omega-3 fatty acid supplements and enriched foods to get and maintain adequate amounts of these fatty acids. The aim of this paper was to review main scientific evidence regarding the public health risks and benefits of the dietary sources of omega-3 fatty acids. A systematic literature search was performed, and one hundred and forty-five articles were included in the results for their methodological quality. The literature described benefits and risks of algal, fish oil, plant, enriched dairy products, animal-derived food, krill oil, and seal oil omega-3 fatty acids.


Asunto(s)
Dieta , Grasas de la Dieta , Suplementos Dietéticos , Ácidos Grasos Omega-3 , Salud Pública , Animales , Ácidos Grasos Omega-3/efectos adversos , Ácidos Grasos Omega-3/uso terapéutico , Aceites de Pescado , Alimentos Fortificados , Humanos , Aceites de Plantas , Riesgo , Medición de Riesgo
18.
Int J Sports Med ; 33(7): 531-6, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22562744

RESUMEN

The aim was to study the effects of scuba diving immersion on plasma antioxidant defenses, nitric oxide production, endothelin-1 and vascular endothelial growth factor levels. 9 male divers performed an immersion at 50 m depth for a total time of 35 min. Blood samples were obtained before diving at rest, immediately after diving, and 3 h after the diving session. Leukocyte counts, plasma 8oxoHG, malondialdehyde and nitrite levels significantly increased after recovery. Activities of lactate dehydrogenase, creatine kinase, catalase and superoxide significantly increased immediately after diving and these activities remained high after recovery. Plasma myeloperoxidase activity and protein levels and extracellular superoxide dismutase protein levels increased after 3 h. Endothelin-1 concentration significantly decreased after diving and after recovery. Vascular endothelial growth factor concentration significantly increased after diving when compared to pre-diving values, returning to initial values after recovery. Scuba diving at great depth activated the plasma antioxidant system against the oxidative stress induced by elevated pO2 oxygen associated with hyperbaria. The decrease in endothelin-1 levels and the increase in nitric oxide synthesis could be factors that contribute to post-diving vasodilation. Diving increases vascular endothelial growth factor plasma levels which can contribute to the stimulation of tissue resistance to diving-derived oxidative damage.


Asunto(s)
Antioxidantes/metabolismo , Buceo/fisiología , Óxido Nítrico/biosíntesis , Estrés Oxidativo , Adulto , Endotelina-1/metabolismo , Humanos , Masculino , Malondialdehído/metabolismo , Oxígeno/metabolismo , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Vasodilatación
19.
Bone Marrow Transplant ; 57(2): 176-182, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34711917

RESUMEN

Traceability of patients who are candidates for Hematopoietic cell transplant (HCT) is crucial to ensure HCT program quality. Continuous knowledge of both a detailed registry from a HCT program and final exclusion causes can contribute to promoting a real-life vision and optimizing patient and donor selection. We analyzed epidemiological data reported in a 4 year-monocentric prospective registry, which included all patients presented as candidates for autologous (Auto) and/or allogeneic (Allo) HCT. A total of 543 patients were considered for HCT: 252 (42.4%) for Allo and 291 (57.6%) for Auto. A total of 98 (38.9%) patients were excluded from AlloHCT due to basal disease progression more commonly (18.2%). Seventy-six (30.2%) patients had an HLA identical sibling, whereas 147 (58.3%) patients had only Haplo. UD research was performed in 106 (42%) cases, significantly more often in myeloid than lymphoid malignancies (57% vs 28.7%, p < 0.001) but 61.3% were finally canceled, due to donor or disease causes in 72.4%. With respect to Auto candidates, a total of 60 (20.6%) patients were finally excluded; progression was the most common cause (12%). Currently, Haplo is the most frequent donor type. The high cancellation rate of UD research should be revised to optimize further donor algorithms.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Selección de Donante , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Sistema de Registros , Acondicionamiento Pretrasplante , Trasplante Autólogo
20.
Chemosphere ; 280: 130575, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33957472

RESUMEN

Aquaculture is a potential source of microplastics (MPs) that could be strong stressors for marine organisms. In this study, we evaluated the effects of MPs derived from aquaculture in antioxidant defences and oxidative stress markers in gills of Mytilus galloprovincialis. Mussels were distributed in three areas with different impacts: inside aquaculture cages, Control 1 (located inside Andratx harbour) and Control 2 (located in a no-anthropized area). Samples were obtained along three different time periods in May (T0), July (T60) and in September (T120). At each sampling period, mussels' biometric measurements were taken, and tissue samples were kept frozen for biochemical determinations and to determine the intake of MPs. An increase in MPs intake was detected throughout the study, and this increase was significantly higher in samples from the aquaculture cages. Similarly, antioxidant enzyme activities (catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase) were significantly higher in samples from cages at T120. Additionally, a similar tendency was observed in glutathione-s-transferase, with a higher activity in the aquaculture cages at T60 and T120. Malondialdehyde and carbonyl protein derivates as a marker of oxidative damage were also measured and samples from aquaculture cages presented higher oxidative stress markers, mainly in T120. In conclusion, living in environments exposed to aquaculture activities at sea may imply a higher intake of MPs which in turn might cause an antioxidant response in M. galloprovincialis which is not enough to avoid oxidative damage.


Asunto(s)
Mytilus , Contaminantes Químicos del Agua , Animales , Acuicultura , Biomarcadores/metabolismo , Microplásticos , Mytilus/metabolismo , Estrés Oxidativo , Plásticos , Contaminantes Químicos del Agua/análisis
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