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

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Lack of Specific Immune Response after Five Doses of mRNA SARS-CoV-2 Vaccine in a Patient with CD4⁺ T-Cell Lymphopenia but Preserved Responses to CMV

Immunogenicity of SARS-CoV-2 mRNA vaccines is highly heterogeneous in patients with inborn errors of immunity (IEIs). This case report analyzes the immune response to mRNA COVID-19 two-dose primary vaccination followed by three boosters in an IEI patient with marked CD4+ T-cell cytopenia and diminished thymic output, in comparison with that raised against latent, chronic cytomegalovirus (CMV) infection. Serum IgG antibodies anti-spike (S) protein of SARS-CoV-2 and anti-CMV were both determined by chemiluminescent microparticle immunoassays (CMIAs). SARS-CoV-2 and CMV memory CD4+ T-cell responses were simultaneously evaluated in vitro using an activation-induced marker (AIM) assay via multicolor flow cytometry. Throughout the 2-year follow-up that included the administration of five doses of SARS-CoV-2 mRNA vaccines, cellular anti-SARS-CoV-2-specific responses remained consistently negative, with extremely weak humoral responses, while the patient showed in vitro persistent CD4+ T-cell reactivity to CMV peptides and high-IgG CMV-specific titers. The assessment of immune responses to vaccines and prevalent viruses is essential in IEI patients in order to take adequate preventive measures

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

Survival in primary hemophagocytic lymphohistiocytosis, 2016 to 2021: etoposide is better than its reputation

Böhm S, Wustrau K, Pachlopnik Schmid J, et al. Survival in primary hemophagocytic lymphohistiocytosis, 2016 to 2021: etoposide is better than its reputation. Blood. 2024;143(10):872-881.ABSTRACT: Primary hemophagocytic lymphohistiocytosis (pHLH) is a life-threatening hyperinflammatory syndrome that develops mainly in patients with genetic disorders of lymphocyte cytotoxicity and X-linked lymphoproliferative syndromes. Previous studies with etoposide-based treatment followed by hematopoetic stem cell transplantation (HSCT) resulted in 5-year survival of 50% to 59%. Contemporary data are lacking. We evaluated 88 patients with pHLH documented in the international HLH registry from 2016-2021. In 12 of 88 patients, diagnosis was made without HLH activity, based on siblings or albinism. Major HLH-directed drugs (etoposide, antithymocyte globulin, alemtuzumab, emapalumab, ruxolitinib) were administered to 66 of 76 patients who were symptomatic (86% first-line etoposide); 16 of 57 patients treated with etoposide and 3 of 9 with other first-line treatment received salvage therapy. HSCT was performed in 75 patients; 7 patients died before HSCT. Three-year probability of survival (pSU) was 82% (confidence interval [CI], 72%-88%) for the entire cohort and 77% (CI, 64%-86%) for patients receiving first-line etoposide. Compared with the HLH-2004 study, both pre-HSCT and post-HSCT survival of patients receiving first-line etoposide improved, 83% to 91% and 70% to 88%. Differences to HLH-2004 included preferential use of reduced-toxicity conditioning and reduced time from diagnosis to HSCT (from 148 to 88 days). Three-year pSU was lower with haploidentical (4 of 9 patients [44%]) than with other donors (62 of 66 [94%]; P< .001). Importantly, early HSCT for patients who were asymptomatic resulted in 100% survival, emphasizing the potential benefit of newborn screening. This contemporary standard-of-care study of patients with pHLH reveals that first-line etoposide-based therapy is better than previously reported, providing a benchmark for novel treatment regimes. © 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies