Primary and Secondary Immunodeficiency Diseases in Oncohaematology: Warning Signs, Diagnosis, and Management

Background: Immunodeficiencies (ID), in particular primary immunodeficiencies (PID), are often associated with haematological manifestations, such as peripheral cytopenias or lymphoproliferative syndromes. Early diagnosis and management have significant prognostic implications. Secondary immunodeficiencies (SID) may also be induced by oncohaematological diseases and their treatments. Haematologists and oncologists must therefore be aware of the association between blood disorders and cancer and ID, and be prepared to offer their patients appropriate treatment without delay. Our aim was to define the warning signs of primary and secondary IDs in paediatric and adult patients with oncohaematological manifestations.Methods: A multidisciplinary group of six experts (2 haematologists, 2 immunologists, and 2 paediatricians specializing in ID) conducted a literature review and prepared a document based on agreements reached an in-person meeting. An external group of 44 IDs specialists from all over Spain assessed the document and were consulted regarding their level of agreement.Results: This document identifies the haematological and extra-haematological diseases that should prompt a suspicion of PIDs in adults and children, in both primary care and haematology and oncology departments. Cytopenia and certain lymphoproliferative disorders are key diagnostic pointers. The diagnosis must be based on a detailed clinical history, physical exploration, complete blood count and standard laboratory tests. The immunological and haematological tests included in the diagnostic process will depend on the care level. Patients who are candidates for immunoglobulin replacement therapy must be carefully selected, and treatment should be offered as soon as possible to avoid the development of complications. Finally, this document recommends procedures for monitoring these patients.Conclusions: This document combines scientific evidence with the opinion of a broad panel of experts, and emphasizes the importance of an early diagnosis and treatment to avoid complications. The resulting document is a useful tool for primary care physicians and specialists who see both adult and paediatric patients with oncohaematological diseases

Uso humano del espacio en el alto Caquetá

IP 1103-10-350-95Incluye anexos

A Case of IL-7R Deficiency Caused by a Novel Synonymous Mutation and Implications for Mutation Screening in SCID Diagnosis

International audienceReported synonymous substitutions are generally non-pathogenic, and rare pathogenic synonymous variants may be disregarded unless there is a high index of suspicion. In a case of IL7 receptor deficiency severe combined immunodeficiency (SCID), the relevance of a non-reported synonymous variant was only suspected through the use of additional in silico computational tools, which focused on the impact of mutations on gene splicing. The pathogenic nature of the variant was confirmed using experimental validation of the effect on mRNA splicing and IL7 pathway function. This case reinforces the need to use additional experimental methods to establish the functional impact of specific mutations, in particular for cases such as SCID where prompt diagnosis can greatly impact on diagnosis, treatment, and survival

Primary T-cell immunodeficiency with functional revertant somatic mosaicism in CD247

Depto. de Inmunología, Oftalmología y ORLFac. de MedicinaTRUEMinisterio de Economía y Competitividad (MINECO)Instituto de Salud Carlos III (ISCIII)Comunidad de MadridFundacion LairUniversidad Complutense de Madridpu

Ethic narratives for rethinking the world: didactic open resources, workshops and graphic narratives reading club

Este proyecto de innovación docente, continuación del proyecto Innova 117 (2020-21), da visibilidad al medio del cómic y a su estudio en el contexto universitario a través de actividades didácticas y formativas dirigidas al estudiantado y al profesorado de las facultades de Filología y Educación. Incluye un club de lectura de cómic de contenido ético enmarcado en los principios de la Agenda 2030, una serie de talleres críticos impartidos por investigadores y estudiantes y varios talleres instrumentales de edición de audio, traducción y didáctica. El proyecto tiene como objetivos principales fomentar el aprendizaje creativo, colaborativo, horizontal y entre pares.This teaching innovation project, which is the continuation of the former innovation project 117 (2020-21), focuses on comics and their study in the university context through didactic and training activities addressed to students and staff of the Faculty of Philology and Education. It includes a reading club (comics with ethic content that breach some of the principles included in the Agenda 2030), several workshops of applied critical theory (taught by students and staff) and several instrumental workshops on audio edition, translation and didactic. One of the main objectives is fostering creative, collaborative and peer-to-peer learning.Depto. de Estudios Ingleses: Lingüística y LiteraturaDepto. de Estudios Románicos, Franceses, Italianos y TraducciónFac. de FilologíaFALSEVicerrectorado de Calidadsubmitte

No Evidence that CD33 rs12459419 Polymorphism Predicts Gemtuzumab Ozogamicin Response in Consolidation Treatment of Acute Myeloid Leukemia Patients: Experience of the PETHEMA Group.

Gemtuzumab ozogamicin (GO) is a conjugate of a monoclonal antibody and calicheamicin, which has been reapproved for the treatment of acute myeloid leukemia (AML). AML patients with the CD33 rs12459419 CC genotype might benefit from the addition of GO to intensive treatment in contrast to patients with CT/TT genotypes. Nevertheless, contradictory results have been reported. We sought to shed light on the prediction of GO response in AML patients with rs12459419 polymorphism who were treated with GO in the consolidation (n = 70) or reinduction (n = 20) phase. The frequency distribution of the rs12459419 polymorphism in the complete cohort of patients was 44.4% (n = 40), 50% (n = 45), and 5.6% (n = 5) for CC, CT, and TT genotypes, respectively. Regarding the patients treated with GO for consolidation, we performed a Kaplan-Meier analysis of overall survival and relapse-free survival according to the rs12459419 polymorphism (CC vs. CT/TT patients) and genetic risk using the European Leukemia Net (ELN) 2010 risk score. We also carried out a Cox regression analysis for the prediction of overall survival, with age and ELN 2010 as covariates. We found no statistical significance in the univariate or multivariate analysis. Additionally, we performed a global Kaplan-Meier analysis for the patients treated with GO for reinduction and did not find significant differences; however, our cohort was too small to draw any conclusion from this analysis. The use of GO in consolidation treatment is included in the approval of the compound; however, evidence regarding its efficacy in this setting is lacking. Rs12459419 polymorphism could help in the selection of patients who might benefit from GO. Regrettably, in our cohort, the rs12459419 polymorphism does not seem to be an adequate tool for the selection of patients who might benefit from the addition of GO in consolidation cycles

Executive Summary of the Consensus Document on the Diagnosis and Management of Patients with Primary Immunodeficiencies

Primary immunodeficiencies (PIDs) are rare, undiagnosed and potentially fatal diseases. Clinical manifestations of PID can be fatal or leave sequelae that worsen the quality of life of patients. Traditionally, the treatment of PIDs has been largely supportive, with the exception of bone marrow transplantation and, more recently, gene therapy. The discovering of new affected pathways, the development of new molecules and biologics, and the increasing understanding of the molecular basis of these disorders have created opportunities in PIDs therapy. This document aims to review current knowledge and to provide recommendations about the diagnosis and clinical management of adults and childre with PIDs based on the available scientific evidence taking in to account current practice and future challenges. A systematic review was conducted, and evidence levels based on the available literature are given for each recommendation where available. � 2020 American Academy of Allergy, Asthma & Immunology; Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [Published by Elsevier Inc./Elsevier Espana]. All rights reserved