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 TratamientoRESUMEN
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 â1 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 JovenRESUMEN
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.
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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 numéricosRESUMEN
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.
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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 , EspañaRESUMEN
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 TratamientoRESUMEN
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.
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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 JovenRESUMEN
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.
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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 JovenRESUMEN
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.
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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 JovenRESUMEN
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.
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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/metabolismoRESUMEN
Coastal ecotones can disrupt natural conditions, yielding intricate ecological contexts where salinity plays a variable role. The aim of this study was to assess the salinity effect on three species representatives of semifixed dune (Crucianella maritima, Helianthemum caput-felis and Teucrium dunense). Field data were collected to assess plant cover in semifixed dunes, ecotone with other coastal habitats, and artificial Posidonia oceanica wracks. Soil samples were collected, and conductivity measured. Then, experimental exposure to salinity was conducted with 6 seawater (SW) treatments (Control, 6.25 % SW, 12.5 % SW, 25 % SW, 50 % SW, 100 % SW). Flowering, gas exchange, chlorophyll fluorescence and enzymatic antioxidant measurements were conducted after two months of exposure. In the field trial, species presence varied depending on the habitat and was null on P. oceanica. The relation between conductivity and species abundance showed moderate tolerance for the three species. For C. maritima this relation was variable depending on the habitat. Experimental data suggest moderate tolerance with stress occurring at 25 % SW onwards. Gas exchange response to salinity was similar among species, but more drastic reduction in assimilation rate and larger decrease in water use efficiency was observed for C. maritima. Instead, photoinhibition occurred in H. caput-felis and T. dunense but was absent in C. maritima likely related to the fact that H. caput-felis and T. dunense activated catalase and superoxide dismutase enzymes, while C. maritima showed activation of glutathione-related enzymes. Malondialdehyde (MDA) increased in C. maritma and decreased for the other species indicating a more complex involvement of MDA under stress conditions. Flowering response to salinity was overall more resilient in T. dunense. Our results, based on field conductivity data and measurements of physiological, antioxidant, and reproductive traits, delineate specific tolerance differences and strategies towards salinity for Mediterranean semifixed dune species.
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Salinidad , Estrés Salino , Ecosistema , Agua de Mar/química , Alismatales/fisiología , Tolerancia a la Sal/fisiología , Brassicaceae/fisiologíaRESUMEN
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.
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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 RetrospectivosRESUMEN
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.
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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 JovenRESUMEN
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.
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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 , RecurrenciaRESUMEN
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 adversosRESUMEN
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.