La terapia CAR-T, una revolución en el abordaje del cáncer.

Introducción: La terapia CAR-T está indicada en el tratamiento de la leucemia linfoblástica aguda de células B refractaria o en recaída (LLA-B R/R) en pacientes <25 años, y en el tratamiento del linfoma B difuso de células grandes (LBDCG) en recaída o refractario en pacientes adultos. Sin embargo, la presente revisión se centrará únicamente en el tratamiento de la LLA-B R/R. La LLA-B es la leucemia más común en niños y en adolescentes <20 años, y es el segundo cáncer más frecuente en la infancia. Aunque el tratamiento de la LLA-B suele ser efectivo, hay casos de LLA-B R/R que no responden al tratamiento, para los cuales estaría indicada la terapia CAR-T, la cual consiste en la extracción de los linfocitos T del paciente, y su reprogramación insertando un receptor de antígeno quimérico (CAR), para que sean capaces de atacar las células tumorales al reconocer sus receptores. Objetivos: Realizar una revisión bibliográfica para valorar los avances de la terapia CAR-T en la LLA-B R/R. Material y métodos: Se ha llevado a cabo una búsqueda bibliográfica en la base de datos MEDLINE vía PubMed, utilizando los descriptores (DeCS/MeSH), los criterios de inclusión y exclusión correspondientes. Resultados: La terapia CAR-T muestra eficacia en todos los estudios analizados. Las dosis elevadas de células CAR-T y la carga tumoral aumentan los riesgos de síndrome de liberación de citocinas severas y neurotoxicidad. No obstante, existen biomarcadores séricos que permiten evaluar el riesgo de toxicidad y aplicar una estrategia de intervención temprana. La adición de fludarabina/ciclofosfamida como quimioterapia linfodepletiva mejoró la persistencia de las células CAR-T y la supervivencia libre de enfermedad. Conclusiones: La terapia CAR-T es una potente terapia celular que ofrece una nueva oportunidad de tratamiento para la LLA-B R/R, aunque el perfil de toxicidad es alto, por lo que se debe seguir mejorando la terapia e intentar disminuir sus riesgos para mejorar los resultados

Actinomyces in Chronic Granulomatous Disease: An Emerging and Unanticipated Pathogen

Background.Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system that causes defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections, mostly by catalase-producing organisms. We report for the first time, to our knowledge, chronic infections with Actinomyces species in 10 patients with CGD. Actinomycosis is a chronic granulomatous condition that commonly manifests as cervicofacial, pulmonary, or abdominal disease, caused by slowly progressive infection with oral and gastrointestinal commensal Actinomyces species. Treatment of actinomycosis is usually simple in immunocompetent individuals, requiring long-term, high-dose intravenous penicillin, but is more complicated in those with CGD because of delayed diagnosis and an increased risk of chronic invasive or debilitating disease. Methods.Actinomyces was identified by culture, staining, 16S ribosomal DNA polymerase chain reaction, and/or a complement fixation test in 10 patients with CGD. Results.All 10 patients presented with a history of fever and elevated inflammatory signs without evident focus. Diagnosis was delayed and clinical course severe and protracted despite high-dose intravenous antibiotic therapy and/or surgery. These results suggest an unrecognized and unanticipated susceptibility to weakly pathogenic Actinomyces species in patients with CGD because these are catalase-negative organisms previously thought to be nonpathogenic in CGD. Conclusions.Actinomycosis should be vigorously sought and promptly treated in patients with CGD presenting with uncommon and prolonged clinical signs of infection. Actinomycosis is a catalase-negative infection important to consider in CG

Clonal Spread of Streptococcus pyogenes emm44 among Homeless Persons, Rennes, France

International audienc

Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor β1 Deficiency: Medical and Immunological Implications

The clinical phenotype of interleukin 12 receptor β1 chain (IL-12Rβ1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rβ1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rβ1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most

The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence

Trost E, Ott L, Schneider J, et al. The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence. BMC Genomics. 2010;11(1): 728

Détection par PCR en temps réel de l'Opéron ica chez Staphylococcus epidermidis (application à l'étude de l'infection liée au cathéter veineux central au sein d'une population pédiatrique d'immunodéprimés)

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Opéron ica et production de biofilm par S. epidermidis (développement et évaluation d'une technique de PCR au sein d'une population de neurochirurgie pédiatrique porteuse d'une dérivation ventriculaire)

PARIS-BIUP (751062107) / SudocSudocFranceF

Epidemiologie clinique et moléculaire des infections à streptococcus pyogenes en Bretagne, 2009-2010

Streptococcus pyogenes est une bactérie strictement inféodée à l'homme responsable d'infections bénignes comme graves. Notre étude a consisté à suivre l'épidémiologie de ces infections entre 2009 et 2010 dans plusieurs centres bretons volontaires. L'analyse des isolats a été réalisée par génotypage du gène emm. Le recueil a initialement révélé l'existence de cas groupés dans une population défavorisée de Rennes, associés au génotype emm44 rare en France mais également la présence de souches identiques dans d'autres secteurs. L'analyse des tableaux cliniques a objectivé une forte prédominance de pathologies cutanées, notamment des dermo-hypodermites. Enfin, l'analyse des infections dues au génotype emm28, le plus fréquent, a montré une forte association avec l'anite de 'enfant. Bien que non exhaustive, cette étude prospective nous a permis de mettre en évidence l'emergence d'un clone épidémique et d'établir une épidémiologie moléculaire des infections streptococciques en Bretagne.Streptococcus pyogenes is a bacteria commonly responsible of various infections, benign or more invasive ones. Our study offers the opportunity to achieve clinical, microbiological and epidemiological portrait of streptococcal infections in Brittany. During the first year we focused on Rennes area and identified an outbreak, in homeless and IV drug users, due to the uncommon emm.44 type isolates. In 2010, we enlarged surveillance to Brittany counties and identified other emm44 indicating an epidemic spreading of a single clone. The most frequent strptococcal infection was cutaneous. We found that emm28 strains were strongly associated with pediatric anitis. Prospective strain recovery, although not-exhaustive, provides an opportuity to identify an emm44 outbreak and to improve our epidemiological understanding of streptococcal infections in Brittany.LYON1-BU Santé (693882101) / SudocRENNES1-BU Santé (352382103) / SudocSudocFranceF

Acute Budd-Chiari syndrome in pediatric acute promyelocytic leukemia.

International audienc