Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL)

© 2021 The Author(s).The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.This project was supported by the AECC (GC16173697BIGA); ISCIII (PI19/01828) co-funded by ERDF/ESF "A way to make Europe"/ "Investing in your future", CERCA/Generalitat de Catalunya SGR 2017 288 (GRC)/ “La Caixa” P. Barba was supported by the Instituto de Salud Carlos III FIS16/01433 and PERIS 2018-2020 from Generalitat de Catalunya (BDNS357800)

Daratumumab is a safe and effective rescue therapy for multiple myeloma patients who relapse after allo-HSCT

This study was supported in part by the Spanish grant of Instituto de Salud Carlos III (PI16/01485) and FEDER European Union.Peer reviewe

The advertising as a tool for social inclusion in children with Down syndrome in the campaign “Compromiso Babysec”

El tema que se presenta en esta investigación se centra en la publicidad como herramienta de inclusión de niños con síndrome de Down en Lima Metropolitana. A pesar de los esfuerzos que está haciendo el Estado peruano para organizar y cuantificar a las personas que tienen alguna discapacidad, no todos están inscritos en el Registro Nacional de Persona con Discapacidad; por lo tanto, no pueden acceder al apoyo que les brinda el Estado y se genera una exclusión social. El caso que se analiza es “Compromiso Babysec”, una campaña de éxito en América del Sur y en el 2019 lanzaron la versión peruana. La relevancia de este trabajo es porque no existen muchas investigaciones que determinen la importancia de la publicidad como herramienta frente a este tema social. De esta manera, el objetivo principal de la investigación es analizar de qué manera la campaña “Compromiso Babysec” puede incentivar la inclusión social en niños con síndrome de Down en Lima Metropolitana. Esta investigación se realizará con una metodología cualitativa bajo la técnica de entrevista a profundidad. En primer lugar, se considerará a madres de 35 a 45 años de nivel socioeconómico B que tengan hijos con síndrome de Down de cero a diez años y que han sido espectadoras de la campaña “Compromiso Babysec”. En segundo lugar, serán madres de 30 a 40 años de nivel socioeconómico B con hijos de cero a diez años que no tienen síndrome de Down y que han sido espectadoras de la campaña “Compromiso Babysec”.This research focuses on advertising as a tool for social inclusion of children with Down syndrome in Metropolitan Lima. In spite of the efforts that the Peruvian State is making to organize and quantify the people who have a disability, not all of them are registered in the National Registry of Persons with Disabilities; therefore, they can not access to the support provided by the State and social exclusion is generated. The case under analysis is "Compromiso Babysec" (Commitment Babysec), a successful campaign in South America; which was launched in Peru in 2019. The relevance of this work resides in the fact that there are not many investigations that focus on the importance of advertising as a tool against this social issue. This is why the main objective of the research is to analyze how the campaign "Compromiso Babysec" can encourage social inclusion of children with Down syndrome in Metropolitan Lima. This research will be carried out according to a qualitative methodology under the technique of in-depth interview. Thus, two target audiences will be considered: first, mothers of 35 to 45 years of age of the socioeconomic status B who have children with Down syndrome from zero to ten years of age and who have been spectators of the "Compromiso Babysec" campaign. Secondly, mothers from 30 to 40 years of age the socioeconomic status B with children from zero to ten years of age who do not have Down syndrome and who have been spectators of the "Compromiso Babysec" campaign.Trabajo de investigació

Effectiveness of antidepressants in improving the prognosis of COVID-19: A systematic review and meta-analysis

Objective, and material and methods: A systematic review and meta-analysis was performed to evaluate the effectiveness of antidepressants in reducing the poor evolution of COVID-19 disease (a composite variable including death, hospitalization and need for mechanical ventilation), and mortality, according the guidelines for Systematic Reviews of Interventions published by the Cochrane library. Source of data: MEDLINE, EMBASE and COCHRANE LIBRARY were consulted up to February 25, 2022. Unpublished studies were searched on clinicaltrials.gov platform. Selection of studies: Seven masked and unmasked, observational and experimental studies evaluating death, hospitalization and need for mechanical ventilation were selected. A second subgroup analysis with mortality variable was performed. Data extraction: A full risk of bias assessment was performed addressing issues such as information and confounding bias. ROB2 and Robins-I tools for randomized and no randomized studies were employed respectively. In the quantitative analysis, the risk of publication bias, heterogeneity, estimation of pooled measure and a sensitivity analysis was performed. The pooled final measure was calculated as odds ratio with its correspondent 95% confidence interval. A random effects model was used for this purpose due to the heterogeneity between included studies.Finally, a sensitivity analysis was performed to assess the robustness of final pooled measure. Results: Seven studies were finally considered to calculate the final pooled measure. The effect of intervention was OR 0.73; 95% CI 0.56–0.94. Conclusions: The use of antidepressants, and specially SSRI could be effective for reducing the risk of poor progression of COVID-19 disease. Resumen: Objetivo, y material y métodos: Se realizó una revisión sistemática y un metaanálisis para evaluar la eficacia de los antidepresivos en la reducción de la mala evolución de la enfermedad COVID-19 (variable compuesta que incluye muerte, hospitalización y necesidad de ventilación mecánica), y mortalidad, según las directrices para Revisiones Sistemáticas de Intervenciones publicadas por la biblioteca Cochrane. Fuente de datos: Se consultaron MEDLINE, EMBASE y la biblioteca Cochrane hasta el 25 de febrero de 2022. Se realizaron búsquedas de estudios no publicados en la plataforma clinicaltrials.gov. Selección de estudios: Se seleccionaron estudios observacionales y experimentales, enmascarados y no enmascarados, que evaluaron la muerte, la hospitalización y la necesidad de ventilación mecánica. Se realizó un segundo análisis de subgrupos con la variable mortalidad. Extracción de datos: Se realizó una evaluación completa del riesgo de sesgo que abordó temas como el sesgo de información y los factores de confusión. Se emplearon las herramientas Rob2 y Robins-I para los estudios aleatorios y no aleatorios, respectivamente. En el análisis cuantitativo, se analizó el sesgo de publicación, heterogeneidad, y se estimó la medida combinada global. La medida final se calculó como odds ratio con su correspondiente intervalo de confianza del 95%. Para ello se utilizó un modelo de efectos aleatorios debido a la heterogeneidad entre los estudios incluidos.Finalmente, se realizó un análisis de sensibilidad para evaluar la robustez de la medida final estimada. Resultados: Se consideraron 7 estudios para calcular la medida agrupada final. El efecto de la intervención (tratamiento con antidepresivos) fue OR 0,73; IC 95% 0,56-0,94. Conclusiones: El uso de antidepresivos, y especialmente de ISRS, podría ser eficaz para reducir el riesgo de mala evolución y mortalidad de la enfermedad COVID-19

Unique clinico-biological, genetic and prognostic features of adult early T-cell precursor acute lymphoblastic leukemia

Early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL), was first identified within cases of childhood T-ALL based on its unique immunophenotypic and genetic features of limited (early) T-cell differentiation associated with (some) myeloid and stem cell features.1 Thus ETP-ALL blasts express CD7, dim CD5 (<75% positive cells), in the absence of CD1a and CD8, and positivity for ≥1 myeloid/stem cell related markers (i.e., CD34, CD13 or CD33).21 In turn, ETP-ALL frequently shows myeloid-associated gene alterations such as FLT3, NRAS/KRAS, DNMT3A, IDH1 and IDH2 mutations,43 with lower frequencies of other T-ALL-associated mutations (e.g., NOTCH1 and CDKN2A/B gene mutations).65 The World Health Organization (WHO) 2016 classification of ALL included ETP-ALL for the first time, as a provisional entity,7 but it failed to establish robust diagnostic criteria. Thus, after the first immunophenotypic characterization of ETP-ALL by Coustan-Smith et al.1 the proposed criteria did not allow identification of all ETP-ALL cases as detected by gene expression profiling.2 In addition, the “partial CD5 expression” criterion had a negative impact on the reproducibility of ETP-ALL diagnoses because of the lack of standardization of the method used for its assessment. Because of this, Zuubier et al. proposed refined immunophenotypic criteria by excluding CD5 expression while adding negativity for CD4.2Funding: this project was supported by the Asociación Española Contra el Cáncer (project ref: GC16173697BIGA), PI14/01971 FIS, Instituto Carlos III, CERCA Program/Generalitat de Catalunya, 2014-SGR225 (GRE), Obra Social “La Caixa” . This work was also partially supported by FEDER funds from the ISCIII (PT13/0010/0026, CIBERONC (CB16/12/00284 and CB16/12/00400), Madrid, Spain). P. Barba was supported by the Instituto de Salud Carlos III FIS16/01433 and PERIS 2018-2020 from Generalitat de Catalunya (BDNS357800) grant

Conditioning‐based outcomes after allogeneic transplantation for myeloma following a prior autologous transplant (1991‐2012) on behalf of EBMT CMWP

[Objectives] The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma—reduced intensity conditioning (RIC), non‐myeloablative (NMA), myeloablative conditioning (MAC) or Auto‐AlloHCT—on outcomes in patients who had had a prior autologous transplant.[Methods] A retrospective analysis of the EBMT database (1991‐2012) was performed.[Results] A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto‐Allo transplants. At a median follow‐up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%‐47%), 45% (95% CI 32%‐57%), 19% (95% CI 6%‐32%) and 34% (95% CI 17%‐51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P < .001) but not after 2002 (HR = 1.2, P = .276).[Conclusion] From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches

Increased survival due to lower toxicity for high-risk T-cell acute lymphoblastic leukemia patients in two consecutive pediatric-inspired PETHEMA trials

[Objective and methods]: Pediatric‐inspired regimens have been adopted by several groups as the treatment strategy for adult patients with acute lymphoblastic leukemia (ALL). Whether subsequent modifications of these protocols have led to an improvement in the outcome of patients is uncertain, especially in T‐cell ALL. We analyzed 169 patients with high‐risk T‐cell ALL included in two consecutive trials of the PETHEMA Group (HR‐ALL03 [n = 104] and the more contemporary HR‐ALL11 [n = 65]). [Results]: Patients and disease characteristics were balanced between both groups. Regarding efficacy, we observed a similar complete remission (CR) rate, relapse and disease‐free survival (DFS) between both protocols. Patients included in the HR‐ALL11 trial had better 2‐year overall survival (OS) compared with the HR‐ALL03 (65% [95% CI 51%‐79%] vs 44% [95% CI 34%‐54%], P = 0.026). Regarding toxicity, we observed a better safety profile in the HR‐11 protocol. Irrespective of the protocol, patients with good measurable residual disease (MRD) clearance had a promising outcome without allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in CR1, with 2‐year OS of 67%. [Conclusion]: Patients with T‐cell ALL included in the HR‐11 trial showed better OS than patients in the HR‐03, mostly driven by a reduction of NRM.This work was supported in part by a grant from Generalitat de Catalunya (2017 SGR288 (GRC)); economical support from CERCA Programme/Generalitat de Catalunya and from Fundació Internacional Josep Carreras. The research leading to this invention has received funding from “la Caixa” Foundation. JMR was supported by PI14/01971 from Fondo de Investigaciones Sanitarias. PB was supported by the Instituto de Salud Carlos III FIS16/01433 and PERIS 2018‐2020 from Generalitat de Catalunya (BDNS357800) grants

Política Internacional (no. 8 oct-dic 2020)

La Revista tiene el objetivo de contribuir al desarrollo de las ciencias políticas, así como difundir los logros en política internacional. Se dirige a los profesionales de las relaciones internacionales en Cuba y del resto del mundo