11 research outputs found
Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens
Get PDFFLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability. © 2021, The Author(s)
One-year breakthrough SARS-CoV-2 infection and correlates of protection in fully vaccinated hematological patients
Get PDFThe long-term clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has been little explored. A prospective multicenter registry-based cohort study conducted from December 2020 to July 2022 by the Spanish Transplant and Cell Therapy group, was used to analyze the relationship of antibody response over time after full vaccination (at 3-6 weeks, 3, 6 and 12 months) (2 doses) and of booster doses with breakthrough SARS-CoV-2 infection in 1551 patients with hematological disorders. At a median follow-up of 388 days after complete immunization, 266 out of 1551 (17%) developed breakthrough SARS-CoV-2 infection at median of 86 days (range 7-391) after full vaccination. The cumulative incidence was 18% [95% confidence interval (C.I.), 16-20%]. Multivariate analysis identified higher incidence in chronic lymphocytic leukemia patients (29%) and with the use of corticosteroids (24.5%), whereas female sex (15.5%) and more than 1 year after last therapy (14%) were associated with a lower incidence (p < 0.05 for all comparisons). Median antibody titers at different time points were significantly lower in breakthrough cases than in non-cases. A serological titer cut-off of 250 BAU/mL was predictive of breakthrough infection and its severity. SARS-CoV-2 infection-related mortality was encouragingly low (1.9%) in our series. Our study describes the incidence of and risk factors for COVID-19 breakthrough infections during the initial vaccination and booster doses in the 2021 to mid-2022 period. The level of antibody titers at any time after 2-dose vaccination is strongly linked with protection against both breakthrough infection and severe disease, even with the Omicron SARS-CoV-2 variant
SARS-CoV-2-reactive antibody waning, booster effect and breakthrough SARS-CoV-2 infection in hematopoietic stem cell transplant and cell therapy recipients at one year after vaccination
Get PDFThe kinetics of SARS-CoV-2 reactive IgG antibodies after full vaccination and booster in allogeneic and autologous stem cell transplantation (allo-HSCT, ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) are of utmost importance for estimating risk of infection. A prospective multicenter registry-based cohort study, conducted from December 2020 to July 2022 was used to analyze antibody waning over time, booster effect and the relationship of antibody response and breakthrough infection in 572 recipients (429 allo-HSCT, 121 ASCT and 22 CAR-T cell therapy). A significant decline in antibody titers was observed at 3 and 6 months after full vaccination in recipients without pre-vaccine SARS-CoV-2 infection, whereas recipients infected prior to vaccination showed higher and stable antibody titers over time. In poor responders, a booster dose was able to increase antibody titers in 83% of allo-HSCT and 58% of ASCT recipients but not in CART-T cell recipients [0%] (p < 0.01). One-year cumulative incidence of breakthrough infection was 15%, similar among cell therapy procedures. Immunosuppressive drugs at the time of vaccination [hazard ratio (HR) 1.81, p = 0.0028] and reduced intensity conditioning (HR 0.49, p = 0.011) were identified as the only conditions associated with different risk of breakthrough infection in allo-HSCT recipients. Antibody titers were associated with breakthrough infection and disease severity. No death was observed among the 72 breakthrough infections. Antibody level decay after the first two vaccine doses was common except in recipients with pre-vaccination SARS-CoV-2 infection. Poorly responding allo-HSCT recipients showed a response advantage with the booster as compared to ASCT and, especially, the null response found in CAR-T cell recipients. Antibody titers were positively correlated with the risk of breakthrough SARS-CoV-2 infection which was mainly driven by the immunosuppression status.REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research. We thank the Spanish Society of Hematology (SEHH) for its support in study diffusion.Peer reviewe
Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients
Get PDFPrior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3–6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin’s lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research. We thank the Spanish Society of Hematology (SEHH) for its support on the study. We sincerely want to thanks the invaluable aid of microbiology services for their commitment in SARS-CoV-2-reactive IgG antibody monitoring in these highly immunosuppressed patients from all participating centers. Finally, we also want to thank the patients, nurses, and study coordinators for their foremost contributions in this study.Peer reviewe
Glotopolítica latinoamericana : Tendencias y perspectivas
Get PDFGlotopolítica latinoamericana: tendencias y perspectivas recoge el resultado de presentaciones y deliberaciones del IV Congreso Latinoamericano de Glotopolítica, realizado en la Universidad de San Pablo (Brasil) en septiembre de 2019, que convocó a numerosos y destacados especialistas en el área. Su inscripción en una serie (los anteriores se realizaron en Chile, Colombia y Alemania) nos permite apreciar los grandes ejes de los que da cuenta el cuidadoso e inteligente armado del libro decidido por los editores, y fundamentado en la Presentación. El tramo que hemos recorrido como especialistas, en el cual los eventos internacionales son hitos significativos, ha ido mostrando la amplitud de un campo que se construye apelando a tradiciones académicas variadas, que insiste en su carácter interdisciplinario y crítico y que no deja de tener una dimensión militante que se expone en las reflexiones teóricas, las investigaciones empíricas y las prácticas institucionales
Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy
Get PDFIntroductionScarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era.PurposeTo assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting.MethodsA retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed.ResultsNearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality.ConclusionsThe results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality
NUEVE JUECES ENTRAN EN DIÁLOGO CON NUEVE HIPÓTESIS ACERCA DE LA PRUEBA DE LOS HECHOS EN EL CONTEXTO PENAL
Full text linkEquidad en salud
Full text link•Acceso a diagnóstico y tratamiento para depresión según posición social en países seleccionados de Latinoamérica •Análisis narrativo de experiencias de chilenos exiliados políticos con discapacidad física en Malmö, Suecia •Caracterización y comparación de puérperas peruanas y chilenas atendidas en el Hospital San José •Conocimientos y prácticas de estudiantes de 7º y 8º básico, de ambos sexos, de Curacaví •Desarrollo económico y mortalidad prematura, Chile, 1994-2003 •Determinación nacional del Índice Significante de Caries (SIC) en adolescentes de 12 años, Chile 2010 •Diagnóstico de salud bucal en niños 2 y 4 años asistentes a la educación preescolar, zonas norte y centro •El GES promueve la equidad en el tratamiento del gran quemado de la tercera edad •Evaluación del nivel de conocimiento en salud bucal de la comunidad educativa preescolar •Factores psicosociales y culturales que inciden en embarazo adolescente en niñas menores de 15 años •Índice Significante de Caries en niños de 6 años, Chile 2010 •La mortalidad por cáncer del cuello uterino en Río de Janeiro: Estudio ecológico •Nivel de desarrollo psicomotor y su relación con el score de riesgo DSM •Perfil en interconsultas dermatológicas del consultorio Padre Esteban Gumucio Vives de Santiago de Chile, 2010 •Prevalencia caries, pérdida de dientes, necesidad de tratamiento en adultos mapuche - huilliches de Isla Huapi •Recursos humanos odontológicos para tratamiento de caries en adolescentes de 12 años, Chile 2010 •Retraso del diagnóstico de tuberculosis en la percepción de los representantes de ONG en Río de Janeiro •Rol de la escuela en promoción de salud y reducción de vulnerabilidad social en salud •Tendencia de las tasas de mortalidad fetal e infantil y sus componentes, Chile 1996- 2006 •Implementación de un mamógrafo móvil para la Región de los Río
SARS-CoV-2 vaccine response and rate of breakthrough infection in patients with hematological disorders
Get PDFBackground The clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has not yet been established. Patients and methods A prospective multicenter registry-based cohort study conducted from December 2020 to December 2021 by the Spanish transplant and cell therapy group was used to analyze the relationship of antibody response at 3-6 weeks after full vaccination (2 doses) with breakthrough SARS-CoV-2 infection in 1394 patients with hematological disorders. Results At a median follow-up of 165 days after complete immunization, 37 out of 1394 (2.6%) developed breakthrough SARS-CoV-2 infection at median of 77 days (range 7-195) after full vaccination. The incidence rate was 6.39 per 100 persons-year. Most patients were asymptomatic (19/37, 51.4%), whereas only 19% developed pneumonia. The mortality rate was 8%. Lack of detectable antibodies at 3-6 weeks after full vaccination was the only variable associated with breakthrough infection in multivariate logistic regression analysis (Odds Ratio 2.35, 95% confidence interval 1.2-4.6, p = 0.012). Median antibody titers were lower in cases than in non-cases [1.83 binding antibody units (BAU)/mL (range 0-4854.93) vs 730.81 BAU/mL (range 0-56,800), respectively (p = 0.007)]. We identified 250 BAU/mL as a cutoff above which incidence and severity of the infection were significantly lower. Conclusions Our study highlights the benefit of developing an antibody response in these highly immunosuppressed patients. Level of antibody titers at 3 to 6 weeks after 2-dose vaccination links with protection against both breakthrough infection and severe disease for non-Omicron SARS-CoV-2 variants
Equidad en salud
Get PDF•Acceso a diagnóstico y tratamiento para depresión según posición social en países seleccionados de Latinoamérica •Análisis narrativo de experiencias de chilenos exiliados políticos con discapacidad física en Malmö, Suecia •Caracterización y comparación de puérperas peruanas y chilenas atendidas en el Hospital San José •Conocimientos y prácticas de estudiantes de 7º y 8º básico, de ambos sexos, de Curacaví •Desarrollo económico y mortalidad prematura, Chile, 1994-2003 •Determinación nacional del Índice Significante de Caries (SIC) en adolescentes de 12 años, Chile 2010 •Diagnóstico de salud bucal en niños 2 y 4 años asistentes a la educación preescolar, zonas norte y centro •El GES promueve la equidad en el tratamiento del gran quemado de la tercera edad •Evaluación del nivel de conocimiento en salud bucal de la comunidad educativa preescolar •Factores psicosociales y culturales que inciden en embarazo adolescente en niñas menores de 15 años •Índice Significante de Caries en niños de 6 años, Chile 2010 •La mortalidad por cáncer del cuello uterino en Río de Janeiro: Estudio ecológico •Nivel de desarrollo psicomotor y su relación con el score de riesgo DSM •Perfil en interconsultas dermatológicas del consultorio Padre Esteban Gumucio Vives de Santiago de Chile, 2010 •Prevalencia caries, pérdida de dientes, necesidad de tratamiento en adultos mapuche - huilliches de Isla Huapi •Recursos humanos odontológicos para tratamiento de caries en adolescentes de 12 años, Chile 2010 •Retraso del diagnóstico de tuberculosis en la percepción de los representantes de ONG en Río de Janeiro •Rol de la escuela en promoción de salud y reducción de vulnerabilidad social en salud •Tendencia de las tasas de mortalidad fetal e infantil y sus componentes, Chile 1996- 2006 •Implementación de un mamógrafo móvil para la Región de los Río
