Author: "Haematology Department" - Searchworks@Jio Institute Digital Library Search Results

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3,730 results on '"Haematology Department"'

1. HODGKIN'S DISEASE AND LYMPHOMA

Author: BARRY O'NEILL and Haematology Department
Subjects: Oncology, medicine.medical_specialty, Hodgkin s, business.industry, Internal medicine, medicine, General Medicine, Disease, medicine.disease, business, Lymphoma
Published: 1962

2. Relationship between ABO Blood Group Distribution and COVID-19 Infection in Patients Admitted to the ICU: A Multicenter Observational Spanish Study

Author: Jericó, Carlos, Zalba-Marcos, Saioa, Quintana-Díaz, Manuel, López-Villar, Olga, Santolalla-Arnedo, Iván, Abad-Motos, Ane, Laso-Morales, María Jesús, Sancho, Esther, Subirà, Maricel, Bassas, Eva, Ruiz de Viñaspre-Hernández, Regina, Juárez-Vela, Raúl, García-Erce, José Antonio, http://orcid.org/0000-0001-6705-7122, http://orcid.org/0000-0002-6978-2501, http://orcid.org/0000-0003-0345-8028, http://orcid.org/0000-0003-3597-2048, http://orcid.org/0000-0001-7662-6286, [Jericó C] Internal Medicine Department, Complex Hospitalari Moisés Broggi, Sant Joan Despí, Spain. [Zalba-Marcos S] Haematology Department, Hospital Universitario de Navarra, Pamplona, Spain. [Quintana-Díaz M] PBM Research Group, Idi-Paz Research Institute, Madrid, Spain. Intensive Care Unit, Hospital Universitario La Paz, Madrid, Spain. [López-Villar O] Transfusion Service, Haematology Department, Hospital Universitario de Salamanca, Salamanca, Spain. [Santolalla-Arnedo I] Department of Nursing-GRUPAC, University of La Rioja, Logroño, Spain. [Abad-Motos A] Anaesthesia Department, Hospital Universitario Infanta Leonor, Madrid, Spain. [Sancho E] Haematology Department, Hospital General de Granollers, Granollers, Spain, and Hospital General de Granollers
Subjects: coronavirus infections, multivariate analysis, ABO blood-group system, Grups sanguinis, factores biológicos::antígenos::antígenos de superficie::antígenos de grupos sanguíneos::sistema del grupo sanguíneo ABO [COMPUESTOS QUÍMICOS Y DROGAS], Biological Factors::Antigens::Antigens, Surface::Blood Group Antigens::ABO Blood-Group System [CHEMICALS AND DRUGS], General Medicine, Epidemiologia, COVID-19 (Malaltia)
Abstract: ABO blood-group system; Coronavirus infections; Multivariate analysis. Sistema de grups sanguinis ABO; Infeccions per coronavirus; Anàlisi multivariant Sistema de grupos sanguíneos ABO; Infecciones por coronavirus; Análisis multivariable Since the beginning of the COVID-19 pandemic in December 2019, a relationship between the ABO blood group type and the novel coronavirus SARS-CoV-2, the etiological agent of COVID-19, has been reported, noting that individuals with the O blood group are the least likely to be infected. Spain is one of the most badly affected countries worldwide, with high rates of patients diagnosed, hospitalized, and deceased due to COVID-19 infection. The present study aimed to analyze the possible relationship of ABO in COVID-19 patients hospitalized in different Spanish centers during the first wave of the COVID-19 pandemic, for which the ABO group was available. Physicians from the transfusion services of different Spanish hospitals, who have developed a multicenter retrospective observational study, were invited to participate voluntarily in the research and 12,115 patients with COVID-19 infection were admitted to the nine participating hospitals. The blood group was known in 1399 cases (11.5%), of which 365 (26.1%) were admitted to the ICU. Regarding the distribution of ABO blood groups, a significant increase in the non-O blood groups and reduction for the O blood group was observed in patients hospitalized due to COVID-19, compared to the reference general population. Among the patients admitted to the ICU, after multivariate analysis, adjusted for the rest of the confounding variables, patients with the O blood group presented a significantly lower risk for admission to the ICU. We conclude that an association was observed between patients with the O blood group and their lower susceptibility to SARS-CoV-2 infection, both for those admitted to the hospitalization ward and for those who required admission to the ICU.
Published: 2022

3. Immunogenicity and safety of the meningococcal B recombinant (4CMenB) vaccine in allogeneic hematopoietic cell transplantation recipients

Author: Christine, Robin, Rabah, Redjoul, Aude, Terrade, Ala-Eddine, Deghmane, Ludovic, Cabanne, Catherine, Cordonnier, Muhamed-Kheir, Taha, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Infections Bactériennes Invasives - Invasive Bacterial Infections, Institut Pasteur [Paris] (IP), Centre National de Référence des Méningocoques et Haemophilus influenzae - National Reference Center Meningococci and Haemophilus influenzae (CNR), and The authors are grateful to the laboratory staff of the Invasive Bacterial Infections Unit at the Institut Pasteur, Paris, France. They are also grateful to the staff of the Haematology Department, Pr Sébastien Maury, of the Plateforme de Recherche Biologique, Pr Bijan Ghaled-Marsban and Dr Caroline Barau, and of the Unité de Recherche Clinique, Pr Sylvie Bastuji-Garin, Henri Mondor hospital.
Subjects: Male, Adult, Microbiology (medical), Antigens, Bacterial, [SDV]Life Sciences [q-bio], Vaccination, Hematopoietic Stem Cell Transplantation, Meningococcal Vaccines, General Medicine, Neisseria meningitidis, Serogroup B, Allogeneic hematopoietic cell transplantation, Meningococcal B vaccine, Antibodies, Bacterial, Meningococcal Infections, Bactericidal assays, Infectious Diseases, Humans, Neisseria meningitidis infection, Vaccine response
Abstract: International audience; ObjectivesDespite a high risk of invasive meningococcal (Men) disease, there is no published data on any MenB vaccine after hematopoietic cell transplantation (HCT). We investigated the immunogenicity and safety of the 4CMenB recombinant vaccine (Bexsero) in adult HCT recipients.MethodsPatients were eligible from 6 months post-HCT to receive 2 4CMenB doses at 2-month intervals. Sera were collected at baseline, 1 month after the second dose, and 12 months after enrolment. The serum bactericidal activity (SBA) using human complement (hSBA) was assessed against fHbp, NadA, PorAP1.4, and NHBA antigens. The vaccine response was defined by one criterion for one vaccine antigen: (1) in patients with a hSBA titer
Published: 2022

4. High frequency of exon 15 deletion in the FANCA gene in Tunisian patients affected with Fanconi anemia disease: implication for diagnosis

Author: Sondes H Meseddi, Koussay Dellagi, Dominique Stoppa Lyonnet, Olfa Messaoud, Jean Soulier, Tarek Ben Othmen, Mongia Hachicha, Fethi Mellouli, Sonia Abdelhak, Catherine Dubois d'Enghien, Mohamed Bejaoui, Ahlem Amouri, Faten Talmoudi, Héla Azaiez, Lamia Aissaoui, Tunisian Fanconi, Mariem Ben Rekaya, Rym Kefi, Ines Allegui, Lamia Torjemane, Ahlem Abdelhak, Hela Ben Abid, Monia Ouederni, Département d'Histologie et de Cytogénétique - Institut Pasteur de Tunis, Institut Pasteur de Tunis-Réseau International des Instituts Pasteur ( RIIP ), Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory ( LR11IPT05 ), Université Tunis El Manar ( UTM ) -Institut Pasteur de Tunis-Réseau International des Instituts Pasteur ( RIIP ), Department of tumor biology, Institut Curie, Institut Curie-Institut Curie, Haematology Department, Hedi Chaker Hospital, University of Sfax, Department of Haematology and Transplantation, National Bone Marrow Transplantation Centre, Department of Peadiatric Immuno-Haematology, National Bone Marrow Transplantation, Haematology Department, Aziza Othmana Hospital, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Sorbonne Paris Cité ( USPC ), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Department of Pediatrics, CHU Hedi Chaker, Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection ( LR11IPT02 ), This study was supported by the Tunisian Ministry of Higher Education and Scientific Research (Laboratory of 'Biomedical Genomics and Oncogenetics' LR11IPT05) and by the Tunisian Ministry of Health., The Tunisian Fanconi Anemia Study Group, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory (LR11IPT05), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Institut Curie [Paris], Hedi Chaker Hospital [Sfax], Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), and Pasteur Tunis, Institut
Subjects: Genetic counseling, [SDV]Life Sciences [q-bio], founder haplotype, Consanguinity, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, Fanconi anemia, Genetics, medicine, Multiplex ligation-dependent probe amplification, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Molecular Biology, Genetics (clinical), [ SDV ] Life Sciences [q-bio], Donor selection, Haplotype, Disease gene identification, medicine.disease, 3. Good health, MLPA, [SDV] Life Sciences [q-bio], [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Exon 15 deletion, founder mutation, Original Article, Founder effect
Abstract: International audience; Tunisian population is characterized by its heterogeneous ethnic background and high rate of consanguinity. In consequence, there is an increase in the frequency of recessive genetic disorders including Fanconi anemia (FA). The aim of this study was to confirm the existence of a founder haplotype among FA Tunisian patients and to identify the associated mutation in order to develop a simple tool for FA diagnosis. Seventy-four unrelated families with a total of 95 FA patients were investigated. All available family members were genotyped with four microsatellite markers flanking FANCA gene. Haplotype analysis and homozygosity mapping assigned 83 patients belonging to 62 families to the FA-A group. A common haplotype was shared by 42 patients from 26 families at a homozygous state while five patients from five families were heterozygous. Among them, 85% were from southern Tunisia suggesting a founder effect. Using multiplex ligation-dependent probe amplification (MLPA) technique, we have also demonstrated that this haplotype is associated with a total deletion of exon 15 in FANCA gene. Identification of a founder mutation allowed genetic counseling in relatives of these families, better bone marrow graft donor selection and prenatal diagnosis. This mutation should be investigated in priority for patients originating from North Africa and Middle East.
Published: 2014

5. Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

Author: Shiach, Caroline [Aintree University Hospitals NHS Foundation Trust, Haematology Department (United Kingdom)]
Published: 2017
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6. Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party

Author: Daikeler, T., Labopin, M., Gioia, M. di, Abinun, M., Alexander, T., Miniati, I., Gualandi, F., Fassas, A., Martin, T., Schwarze, C.P., Wulffraat, N., Buch, M., Sampol, A., Carreras, E., Dubois, B., Gruhn, B., Gungor, T., Pohlreich, D., Schuerwegh, A., Snarski, E., Snowden, J., Veys, P., Fasth, A., Lenhoff, S., Messina, C., Voswinkel, J., Badoglio, M., Henes, J., Launay, D., Tyndall, A., Gluckman, E., Farge, D., EBMT Autoimmune Disease Working, Department of Rheumatology, University Hospital Basel [Basel], Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Haematology Department, Careggi University Hospital, Newcastle General Hospital, Department of Rheumatology & Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biomedicine, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Department of Haematology II, Ospedale San Martino, Neurology & Haematology, George Papanicolau Hospital, Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Paediatric Haematology & Endocrinology, University Children's Hospital, University Medical Center, VU University Medical Center [Amsterdam], Section of Musculoskeletal Disease, University of Leeds, Hospital Universitari Son Espases, Department of Hematology, Hospital Clinic Barcelona, Department of Neurology, University Hospitals Leuven [Leuven], Department of Pediatrics, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Division of Immunology/Hematology/BMT, Charles University Hospital, Leiden University Medical Center (LUMC), Department of Hematology & Oncology, Medical University of Warsaw - Poland, Department of Haematology & Department of Oncology, NHS & University of Sheffield, Great Ormond Street Hospital for Children [London] (GOSH), University of Gothenburg (GU), University Hospital Lund, Dipartimento di Pediatria, Cinica di Oncoematologia Pediatrica, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Hematology & Rheumatology, University Hospital Tübingen, Department of Internal Medicine, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinical Research Unit, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), EULAR Grant & Freiwillige Akademische Gesellschaft Basel, Università degli Studi di Firenze = University of Florence (UniFI), Universiteit Leiden-Universiteit Leiden, University of Sheffield [Sheffield], and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, stem-cell transplantation bone-marrow-transplantation hemolytic-anemia blood, medicine.medical_treatment, Hematopoietic stem cell transplantation, Biochemistry, Autoimmune thrombocytopenia, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Prednisone, immune system diseases, Risk Factors, hemic and lymphatic diseases, Child, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, 3. Good health, Europe, surgical procedures, operative, Treatment Outcome, 030220 oncology & carcinogenesis, Child, Preschool, Rituximab, Female, Autoimmune hemolytic anemia, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Immunology, Autoimmune Diseases, 03 medical and health sciences, Young Adult, Antiphospholipid syndrome, Internal medicine, medicine, Humans, Immunologic Factors, Cyclophosphamide, Glucocorticoids, Retrospective Studies, Autoimmune disease, Lupus erythematosus, business.industry, Infant, Cell Biology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Multivariate Analysis, business, 030215 immunology
Abstract: To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34+ graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.
Published: 2011

7. The EBMT activity survey on hematopoietic-cell transplantation and cellular therapy 2018: CAR-T's come into focus

Author: Passweg, J.R., Baldomero, H., Chabannon, C., Basak, G.W., Corbacioglu, S., Duarte, R., Dolstra, H., Lankester, A.C., Mohty, M., Montoto, S., Latour, R.P. de, Snowden, J.A., Styczynski, J., Yakoub-Agha, I., Kroger, N., European Soc Blood Marrow Transpla, UAM. Departamento de Medicina, University Hospital Basel [Basel], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Medical University of Warsaw - Poland, Universität Regensburg (UR), Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Radboud University Medical Center [Nijmegen], Leiden University Medical Center (LUMC), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Barts Health NHS Trust [London, UK], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Haematology & Department of Oncology, NHS & University of Sheffield, University of Technology and Life Sciences [ Bydgoszcz], CHU Lille, University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gestionnaire, HAL Sorbonne Université 5
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Oncology, medicine.medical_specialty, Myeloid, Medicina, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], medicine.medical_treatment, Hematopoietic stem cell transplantation, Transplantation, Autologous, Article, Cell therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Medicine, Leukaemia, Humans, Transplantation, Homologous, Aplastic anemia, Cellular therapies, Transplantation, Haematological cancer, Receptors, Chimeric Antigen, European Society for Blood and Marrow Transplantation (EBMT), business.industry, Multiple sclerosis, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Lymphoid malignancies, 3. Good health, Europe, Haematopoiesis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Hematopoietic-cell transplantation (HCT), Car t cells, business, 030215 immunology
Abstract: Hematopoietic-cell transplantation (HCT) is widely used for acquired and congenital disorders of the hematopoietic system. Number of transplants performed in Europe and associated countries continues to rise with 47,468 HCT in 42,901 patients [19,630 allogeneic (41%) and 27,838 autologous (59%)] reported by 701 centers in 50 countries in 2018. Main indications were myeloid malignancies 10,679 (25%; 97% allogeneic), lymphoid malignancies 27,318 (64%; 20% allogeneic), solid tumors 1625 (4%; 2.9% allogeneic), and nonmalignant disorders 3063 (7%; 81% allogeneic). This year’s analysis focuses on cellular therapies with the marked growth in CAR T-cell therapies from 151 in 2017 to 301 patients reported in 2018. Other cellular therapy numbers show less significant changes. Important trends in HCT include a 49% increase in allogeneic HCT for chronic phase CML (although transplant numbers remain low) and a 24% increase in aplastic anemia. In autologous HCT, there is an ongoing increase in autoimmune diseases (by 19%), predominantly due to activity in multiple sclerosis. This annual report reflects current activity and highlights important trends, useful for health care planning.
Published: 2020

8. Standardized next-generation sequencing of immunoglobulin and T-cell receptor gene recombinations for MRD marker identification in acute lymphoblastic leukaemia; a EuroClonality-NGS validation study

Author: Brüggemann, Monika, Kotrova, Michaela, Knecht, Henrik, Bartram, Jack, Boudjogrha, Myriam, Bystry, Vojtech, Fazio, Grazia, Froňková, Eva, Giraud, Mathieu, Grioni, Andrea, Hancock, Jeremy, Herrmann, Dietrich, Jimenez, Cristina, Krejci, Adam, Moppett, John, Reigl, Tomas, Salson, Mikaël, Scheijen, Blanca, Schwarz, Martin, Songia, Simona, Svaton, Michael, van Dongen, Jacques, Villarese, Patrick, Wakeman, Stephanie, Wright, Gary, Cazzaniga, Giovanni, Davi, Frédéric, García-Sanz, Ramón, Davi, David, Groenen, Patricia, Hummel, Michael, Macintyre, Elizabeth, Stamatopoulos, Kostas, Pott, Christiane, Trka, Jan, Darzentas, Nikos, Langerak, Anton, Gonzalez, David, Bruggemann, M, Kotrova, M, Knecht, H, Bartram, J, Boudjogrha, M, Bystry, V, Fazio, G, Fronkova, E, Giraud, M, Grioni, A, Hancock, J, Herrmann, D, Jimenez, C, Krejci, A, Moppett, J, Reigl, T, Salson, M, Scheijen, B, Schwarz, M, Songia, S, Svaton, M, van Dongen, J, Villarese, P, Wakeman, S, Wright, G, Cazzaniga, G, Davi, F, Garcia-Sanz, R, Gonzalez, D, Groenen, P, Hummel, M, Macintyre, E, Stamatopoulos, K, Pott, C, Trka, J, Darzentas, N, Langerak, A, Immunology, University Medical Center of Schleswig–Holstein = Universitätsklinikum Schleswig-Holstein (UKSH), Kiel University, Childhood Leukaemia Investigation Prague (CLIP), University Hospital Motol [Prague], Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189 (CRIStAL), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Ecole Centrale de Lille, Facultad de Quimica, Universidad Nacional Autonoma de Mexico, Bioinformatics and Sequence Analysis (BONSAI), Laboratoire d'Informatique Fondamentale de Lille (LIFL), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria), Liebherr-Werk Nenzing GmbH, Department of Immunology, Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bristol Genetics Laboratory, Southmead Hospital, North Bristol NHS Trust, Great Ormond Street Hospital for Children [London] (GOSH), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Haematology Department, University Hospital of Salamanca, Hematology Department and University Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France, Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands., Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, CHU Necker - Enfants Malades [AP-HP], Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden, University Hospital Schleswig–Holstein, Department of Paediatric Haematology/Oncology, Charles University [Prague], Central European Institute of Technology, Masaryk University, Brno, Czech Republic, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Paediatric Haematology, Department of Hematology, University Hospital Schleswig-Holstein [Kiel, Germany], Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Centro Ricerca Tettamanti, Clinica Pediatrica, Ospedale S. Gerardo-Ospedale S. Gerardo, Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Bristol Genetics Laboratory (Southmead Hospital), Southmead Hospital, Instituto de Investigación Biomédica de Salamanca (IBSAL), Department of Pediatric Haematology, Bristol Royal Hospital for Children, Department of Pathology [Nijmegen], Radboud University Medical Center [Nijmegen], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité d'Immunologie et d'Hématologie Pédiatrique (CHU Necker - Enfants Malades [AP-HP]), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Institute of Applied Biosciences, Thessaloniki, Greece., Charles University [Prague] (CU), Centre for Cancer Research and Cell Biology, Queen's University [Belfast] (QUB), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Genetic Markers, 0301 basic medicine, Cancer Research, Neoplasm, Residual, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Receptors, Antigen, T-Cell, Immunoglobulins, Computational biology, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Gene Rearrangement, T-Lymphocyte, Article, DNA sequencing, 03 medical and health sciences, symbols.namesake, All institutes and research themes of the Radboud University Medical Center, 0302 clinical medicine, Genetics research, Multiplex polymerase chain reaction, Humans, Cancer genetics, Recombination, Genetic, Sanger sequencing, minimal residual disease, next generation sequencing immunoglobulin and T-cell receptor, Genes, Immunoglobulin, biology, Computational Biology, High-Throughput Nucleotide Sequencing, Reproducibility of Results, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Gene rearrangement, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Reference Standards, Amplicon, Minimal residual disease, 3. Good health, Genes, T-Cell Receptor, 030104 developmental biology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Oncology, 030220 oncology & carcinogenesis, symbols, biology.protein, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Antibody, Primer (molecular biology)
Abstract: International audience; Amplicon-based next-generation sequencing (NGS) of immunoglobulin (IG) and T-cell receptor (TR) gene rearrangements for clonality assessment, marker identification and quantification of minimal residual disease (MRD) in lymphoid neoplasms has been the focus of intense research, development and application. However, standardization and validation in a scientifically controlled multicentre setting is still lacking. Therefore, IG/TR assay development and design, including bioinformatics, was performed within the EuroClonality-NGS working group and validated for MRD marker identification in acute lymphoblastic leukaemia (ALL). Five EuroMRD ALL reference laboratories performed IG/TR NGS in 50 diagnostic ALL samples, and compared results with those generated through routine IG/TR Sanger sequencing. A central polytarget quality control (cPT-QC) was used to monitor primer performance, and a central in-tube quality control (cIT-QC) was spiked into each sample as a library-specific quality control and calibrator. NGS identified 259 (average 5.2/sample, range 0–14) clonal sequences vs. Sanger-sequencing 248 (average 5.0/sample, range 0–14). NGS primers covered possible IG/TR rearrangement types more completely compared with local multiplex PCR sets and enabled sequencing of bi-allelic rearrangements and weak PCR products. The cPT-QC showed high reproducibility across all laboratories. These validated and reproducible quality-controlled EuroClonality-NGS assays can be used for standardized NGS-based identification of IG/TR markers in lymphoid malignancies.
Published: 2019

9. Extracellular vesicle-based therapeutics for heart repair

Author: Saludas, Laura, Oliveira, Cláudia C., Roncal, Carmen, Ruiz-Villalba, Adrián, Prósper, Felipe, Garbayo, Elisa, Blanco-Prieto, María J., [Saludas,L, Garbayo,E, Blanco-Prieto,MJ] Department of Pharmaceutical Technology and Chemistry, Faculty of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain. [Saludas,L, Roncal,C, Prósper,F, Blanco-Prieto,MJ] Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain. [Oliveira,CC, Ruiz-Villalba,A] Department of Animal Biology, Institute of Biomedicine of Málaga (IBIMA), Faculty of Science, University of Málaga, Málaga, Spain. [Oliveira,CC, Ruiz-Villalba,A] Andalusian Centre for Nanomedicine and Biotechnology (BIONAND), Málaga, Spain. [Roncal,C] Laboratory of Atherothrombosis, Program of Cardiovascular Diseases, CIMA, University of Navarra, Pamplona, Spain. [Roncal,C] Centro de Investigación Biomédica en Red (CIBERCV), Carlos III Institute of Health, Madrid, Spain. [Prósper,F] Program of Regenerative Medicine, CIMA, University of Navarra, Pamplona, Spain. [Prósper,F] Cell Therapy Area and Haematology Department, Clínica Universidad de Navarra, Pamplona, Spain. [Prósper,F] Centro de Investigación Biomédica en Red (CIBERONC), Carlos III Institute of Health, Madrid, Spain., and This work was funded by Spanish Ministry of Economy and Competitiveness (SAF2017-83734-R), the 7th EuroNanoMed-II call for proposals, project NanoHeart n°ANR-16-ENM2-0005-01 and Nano ReHeart AC15/0050. C.O. is supported by the European Union‘s Horizon 2020 research and innovation programme Under the Marie Sklodowska-Curie grant agreement No 713721. A.R.V. was supported by a Juan de La Cierva Fellowship (IJCI-2016-30254) and is supported by a 'I Plan Propio de Incorporación de Doctores' from the University of Málaga, and by the Spanish Ministerio de Ciencia y Universidades (RTI2018-095410-B-I00). E. Garbayo is supported by a 'Ramon y Cajal Fellowship' (RYC2018-025897-I).
Subjects: Targeting, Diseases::Cardiovascular Diseases::Heart Diseases::Myocardial Ischemia::Myocardial Infarction [Medical Subject Headings], Extracellular vesicles, Exosomes, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Communication [Medical Subject Headings], Vesículas extracelulares, Exosomas, Cargo loading, Myocardial infarction, Cardiac repair, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy [Medical Subject Headings], Cardiovascular diseases, Sistemas de liberación de medicamentos, Infarto del miocardio, Drug delivery, Diseases::Cardiovascular Diseases::Heart Diseases [Medical Subject Headings], Phenomena and Processes::Metabolic Phenomena::Metabolism::Biological Transport [Medical Subject Headings], Enfermedades cardiovasculares, Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::Exosomes [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Cell- and Tissue-Based Therapy [Medical Subject Headings], Diseases::Cardiovascular Diseases [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Delivery Systems [Medical Subject Headings]
Abstract: Extracellular vesicles (EVs) are constituted by a group of heterogeneous membrane vesicles secreted by most cell types that play a crucial role in cell-cell communication. In recent years, EVs have been postulated as a relevant novel therapeutic option for cardiovascular diseases, including myocardial infarction (MI), partially outperforming cell therapy. EVs may present several desirable features, such as no tumorigenicity, low immunogenic potential, high stability, and fine cardiac reparative efficacy. Furthermore, the natural origin of EVs makes them exceptional vehicles for drug delivery. EVs may overcome many of the limitations associated with current drug delivery systems (DDS), as they can travel long distances in body fluids, cross biological barriers, and deliver their cargo to recipient cells, among others. Here, we provide an overview of the most recent discoveries regarding the therapeutic potential of EVs for addressing cardiac damage after MI. In addition, we review the use of bioengineered EVs for targeted cardiac delivery and present some recent advances for exploiting EVs as DDS. Finally, we also discuss some of the most crucial aspects that should be addressed before a widespread translation to the clinical arena. Yes
Published: 2021

10. Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

Author: Bertrand Joly, Hagay Sobol, Isabelle Azais, Hervé Avet-Loiseau, Karine Augeul-Meunier, Catherine Le Bris, Delphine Demangel, Maroulio Pertesi, Xavier Leleu, Maria Victoria Revuelta, Maxime Vallée, Manuel Cliquennois, James D. McKay, Aurore Perrot, Aleksandra Butrym, Matthieu Foll, Björn Nilsson, Javier Oliver, Judit Várkonyi, Emeline Perrial, Xiaomu Wei, Artur Jurczyszyn, Gabriele Buda, Marcin Rymko, Cécile Leyronnas, Robert J. Klein, Elżbieta Iskierka-Jażdżewska, Claire Mathiot, Marzena Wątek, Eric Voog, Olivier Decaux, Florence Desquesnes, Jill Corre, Arnon Nagler, Jean Gabriel Fuzibet, Véronique Dorvaux, Jan Maciej Zaucha, Philippe Rodon, Siwei Chen, Denis Caillot, Laurent Garderet, Michel Maigre, Isabelle Leduc, Fabienne Lesueur, Borhane Slama, Sophie Rigaudeau, Philippe Mineur, Norbert Grząśko, Perrine Galia, Rui Manuel Reis, Federico Canzian, Philippe Helias, Yves-Jean Bignon, Marcin Kruszewski, Victor Moreno, Juan Sainz, Nathalie Cheron, Laurent Voillat, Charles Dumontet, Christian Berthou, Marie Beaumont, Brigitte Pegourie, Etienne Paubelle, Marguerite Vignon, Matteo Pelosini, Philippe Casassus, Isabelle Lambrecht, Laure Vincent, Eileen M Boyle, Annette Juul Vangsted, Pascal Bourquard, Laurent Mosser, Margaret Macro, Gerald Marit, Daniele Campa, Brigitte Kolb, Bruno Royer, Jean Fontan, Ramón García-Sanz, Philippe Moreau, Serge Leyvraz, Malgorzata Krawczyk-Kulis, Krzysztof Jamroziak, Joaquin Martinez-Lopez, Bruno Anglaret, Steven M. Lipkin, Nicole Frenkiel, Ofure Obazee, Marek Dudziński, Pascale Cony-Makhoul, Hervé Naman, Andres Jerez, Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Genetic Cancer Susceptibility, Department of Biological Statistics and Computational Biology, Cornell University, Weill Medical College of Cornell University Division of International Medicine and Infectious Diseases, Weill Medical College of Cornell University [New York], Hospices Civils de Lyon (HCL), ProfileXpert, Université de Lyon, LCMT, ProfileXpert, Biomedical Research Institute of Málaga (IBIMA), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathologies biliaires, fibrose et cancer du foie (Inserm UMR_S 938), CHU Saint-Antoine [APHP]-Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [APHP], Sorbonne Universités, UPMC Univ Paris 06, CNRS UMR 7371, INSERM UMR S1146, Laboratoire d'Imagerie Biomédicale, France, parent, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Département de Médecine Interne [CHU Rennes], Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hopital de Périgueux (CH Périgueux), Hopital de Périgueux, Service d'Hématologie, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Henri Duffaut (Avignon), Département Oncologie-Hématologie [Charleroi, Belgium], Grand Hôpital de Charleroi [Belgium], Centre Jean Bernard [Le Mans] (Institut Inter-Régional de Cancérologie), CHU de Fort de France (Service Post-Urgences, Pôle RASSUR), CHU de Fort de France, Hôpital JeanMinjoz, Centre hospitalier de Chartres (Chartres) (Service d'Hémato-Oncologie), Service hématologie (CHU d'Amiens), CHU Amiens-Picardie, Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie [AP-HP Hôpital Saint-Louis], AP-HP Hôpital Saint-Louis, Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], CHU Saint Louis [APHP], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Médecine Interne [CHU Nice] (Hôpital l'Archet), Hôpital l'Archet-Centre Hospitalier Universitaire de Nice (CHU de Nice), Service d'hématologie [CHR Metz-Thionville], Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre Hospitalier de Valence (Unité d'Hématologie), Centre hospitalier de Valence, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hematology Department - Namur Thrombosis and Hemostasis Center (NTHC), UCL Mont-Godinne, Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), CHUV, Lausanne (Departement d'Oncologie), Unité d'Oncologie Médicale, Rodez (Hôpital Jacques Puel, Pôle Medical 2), Unité de coordination en oncogériatrie de Basse-Normandie [Caen] (UCOG Basse-Normandie), CHI Poissy-Saint-Germain, Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, CHG Abbeville (Hématologie), Institut Daniel Hollard [Grenoble], Service d'hématologie et oncologie [Centre Hospitalier de Chalon-sur-Saône William Morey], Centre Hospitalier Chalon-sur-Saône William Morey, Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Intergroupe francophone du myélome (IFM), Service d'Onco-Hématologie, Centre Médical de Bligny, Briis sous Forges, Service Hématologie, CH LYON SUD, Pierre benite, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital Sud-Fancilien, CH Sud-Fancilien, Département d'Hématologie [CHU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU de Nîmes), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hématologie, Oncologie Médicale, Centre Azureen de cancérologie, Centre Azureen de cancérologie, Unité d'hématologie et d'oncologie [Centre Hospitalier de Versailles], Centre Hospitalier de Versailles (CHV), Inserm U1035, Biotherapies des Maladies Genetiques et Cancers, Univ Bordeaux, CHU de Bordeaux, Pole de Biologie et Pathologie, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Rhumatologie [Reims], Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), CHU Montpellier, Department of Clinical Hematology, Montpellier, France, Hospitalier et Universitaire de Pointe-à-Pitre (Oncologie Médicale), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CIBER Epidemiologia y Salud Pùblica [Madrid, Spain] (CIBERESP), Instituto de Salud Carlos III (ISC), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], Barretos Cancer Hospital [São Paulo, Brazil], Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary, Department of Rheumatology, 3rd Department of Internal Medicine, Semmelweis University, Budapest, Departement of Hematology, University Hospital, Bydgoszcz, Department of Hematology, Rigshospitalet, Copenhagen, Denmark, Department of Hematology, Jagiellonian University - Medical College, Gdynia Oncology Center, Gdynia and Department of Oncological Propedeutics, Genomic Oncology Area (GENYO), Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Department of Hematology, Insitute of Hematology and Transfusion Medicine, Warsa, Holycross Cancer Center of Kelce, Hematology Clinic, Kielce, Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Department of Hematology, Medical University of Lodz, Departement of Experimental Hemato-Oncology, Medical University of Lubli (Polish Myeloma Study Group), Servicio de Hematología, Hospital Universitario 12 de Octubre [Madrid], Hematology and Medical Oncology Department, Hospital Morales Meseguer, Murcia (IMIB), Department of Biology, University of Pisa, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Hematology Department, Teaching Hospital No1, Rzeszow, Teaching Hospital N°1, Haematology Department, University Hospital of Salamanca, Hematology Division Chaim Sheba Medical Center, Tel Hashomer, Department of Hematology Copernicus Hospital, Torun, Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Wroclaw Medical University, Department of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Icahn School of Medicine at Mount Sinai [New York] (MSSM), International Agency for Cancer Research (IACR), INSERM 1052, CNRS 5286, CRCL Lyon, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Centre de Recherche en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UPS), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Charleroi (Hématologie et pathologies de la coagulation), Centre Hospitalier Universitaire de Charleroi, Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Oncologie Génétique, de Prévention et Dépistage, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], Département Universitaire Nice (Internal Medicine Department), Hôpital de Nice, Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne-Université Paris 13 (UP13), Laboratoire de diagnostic génétique et moléculaire, Centre Jean Perrin, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), CHU Dijon, Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire de Caen, Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de génomique du myélome [IUCT Oncopole, Toulouse], IUCT Oncopole - Institut Universitaire du Cancer de Toulouse, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], CIBER de Epidemiología y Salud Pública (CIBERESP), Biomarkers and Susceptibility Unit, Catalan Institute of Oncology, Molecular Oncology Research Center [São Paulo, Brazil], Centro de Genomica e Investigacion Oncologica (GENYO), Hospital universitario 12 de Octubre, Holycross Cancer Center of Kielce, Hematology Clinic, Department of Laboratory Medicine Lunds University Hospital Lund, Cornell University [New York], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Centre Jean Bernard [Institut Inter-régional de Cancérologie - Le Mans], Laboratoire d'Hématologie [CHU Amiens], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier de Versailles André Mignot (CHV), Instituto de Salud Carlos III [Madrid] (ISC), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Jonchère, Laurent, Lund University [Lund], Pathologies biliaires, fibrose et cancer du foie [CRSA], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université catholique de Lille (UCL), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Pisa - Università di Pisa, Mines Paris - PSL (École nationale supérieure des mines de Paris), Wrocław Medical University, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes - Faculté de Médecine (UR Médecine), Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cancer Research, Letter, [SDV]Life Sciences [q-bio], MEDLINE, Library science, Myeloma, World health, 03 medical and health sciences, 0302 clinical medicine, Multiple myeloma, immune system diseases, Political science, hemic and lymphatic diseases, Exome Sequencing, Genetics, Humans, Exome, Genetic Predisposition to Disease, Cancer genetics, Exome sequencing, Germ-Line Mutation, ComputingMilieux_MISCELLANEOUS, Exosome Multienzyme Ribonuclease Complex, Extramural, Mieloma múltiple, French, Hematology, language.human_language, 3. Good health, Pedigree, [SDV] Life Sciences [q-bio], Exome/genetics, Exosome Multienzyme Ribonuclease Complex/genetics, Female, Genetic Predisposition to Disease/genetics, Germ-Line Mutation/genetics, Multiple Myeloma/genetics, Whole Exome Sequencing/methods, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Donation, language, Multiple Myeloma, Genètica, International agency
Abstract: French National Cancer Institute (INCA) and the Fondation Francaise pour la Recherche contre le Myelome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myelome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myelome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization
Published: 2019

11. Dyserythropoiesis evaluated by the RED score and hepcidin:ferritin ratio predicts response to erythropoietin in lower-risk myelodysplastic syndromes

Author: Hervé Puy, Pierre Fenaux, Jean-Yves Cahn, Frédérique Verdier, Clara Mariette, Agathe Debliquis, Anne Sophie Alary, Florence Lachenal, Cecile Leyronnas, Olivier Herault, Orianne Wagner-Ballon, Shanti Ame, Zoubida Karim, Alice Rousseau, Bernard Drenou, Agnès Charpentier, Martin Carre, François Dreyfus, Stéphane Cheze, Frédéric Maloisel, Olivier Kosmider, Thibaud Lefebvre, Cécile Bouilloux, F Garban, Sarah Ducamp, Mathieu Meunier, Michaela Fontenay, Borhane Slama, Sophie Park, Andrea Toma, Marie-Christine Jacob, Christian Rose, Kamel Laribi, Selim Corm, Emmanuel Gyan, Valérie Bardet, Bruno Anglaret, Nicolas Chapuis, Gian Matteo Pica, CHU Grenoble, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Haematology Department, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Immunocytologie, EFS, Hématologie-Biologique, Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Centre Hospitalier de Valence (Unité d'Hématologie), Centre hospitalier de Valence, Institut Daniel Hollard [Grenoble], Medipole De Savoie, Centre Hospitalier Henri Duffaut (Avignon), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Le Mans (CH Le Mans), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CH Pierre Oudot Bourgoin-Jallieu, CHU Henri Mondor, Centre Hospitalier Universitaire [Grenoble] (CHU), Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Université du Québec à Montréal = University of Québec in Montréal (UQAM), CNRS GDR 3697 MicroNiT, Centre National de la Recherche Scientifique (CNRS), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Hôpital Ambroise Paré [AP-HP], Service d'hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), karim, zoubida, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université de Tours, and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Ineffective erythropoiesis, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Kaplan-Meier Estimate, medicine.disease_cause, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, hemic and lymphatic diseases, Erythropoiesis, 10. No inequality, Aged, 80 and over, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Flow Cytometry, Prognosis, Recombinant Proteins, 3. Good health, Treatment Outcome, International Prognostic Scoring System, Epoetin Zeta, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, medicine.drug, medicine.medical_specialty, Anemia, Iron, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Article, 03 medical and health sciences, Hepcidins, Hepcidin, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Erythropoietin, Aged, business.industry, Myelodysplastic syndromes, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Ferritin, ROC Curve, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Myelodysplastic Syndromes, Ferritins, biology.protein, business, Biomarkers, 030215 immunology
Abstract: International audience; Erythropoiesis-stimulating agents are generally the first line of treatment of anemia in patients with lower-risk myelodysplastic syndrome. We prospectively investigated the predictive value of somatic mutations, and biomarkers of ineffective erythropoiesis including the flow cytometry RED score, serum growth-differentiation factor-15, and hepcidin levels. Inclusion criteria were no prior treatment with erythropoiesis-stimulating agents, low- or intermediate-1-risk myelodysplastic syndrome according to the International Prognostic Scoring System, and a hemoglobin level 4 (P=0.05) and a hepcidin:ferritin ratio 2000 pg/mL and a hepcidin:ferritin ratio
Published: 2019

12. Nationwide survey on the use of eltrombopag in patients with severe aplastic anemia: a report on behalf of the French Reference Center for Aplastic Anemia

Author: Paul Coppo, Régis Peffault de Latour, Brigitte Dupriez, Gérard Socié, Ana Berceanu, Lionel Adès, Louis Terriou, Natacha Maillard, Julie Abraham, Flore Sicre de Fontbrune, Thierry Leblanc, Driss Chaoui, Marie Balsat, Bernard Drenou, Etienne Lengliné, Emmanuel Raffoux, Gaelle Guillerm, Selim Corm, Pierre Peterlin, Olivier Tournilhac, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Haematology Department, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Département d'hématologie, Centre Hospitalier de Lens, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie clinique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service d'Hématologie, Argenteuil, Centre Hospitalier Victor Dupouy, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital Jean Bernard, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, CHU Saint-Antoine [APHP], Lille Inflammation Research International Center (LIRIC), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Male, medicine.medical_specialty, Pediatrics, Anemia, Eltrombopag, Salvage therapy, Benzoates, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Refractory, Interquartile range, Surveys and Questionnaires, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, Aplastic anemia, ComputingMilieux_MISCELLANEOUS, Aged, Antilymphocyte Serum, Retrospective Studies, Salvage Therapy, business.industry, Anemia, Aplastic, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, Bone Marrow Failure, 3. Good health, Surgery, Transplantation, Platelet transfusion, Hydrazines, Treatment Outcome, chemistry, 030220 oncology & carcinogenesis, Pyrazoles, Female, France, business, 030215 immunology
Abstract: Few therapeutic options are available for patients with aplastic anemia who are ineligible for transplantation or refractory to immunosuppressive therapy. Eltrombopag was recently shown to produce trilineage responses in refractory patients. However, the effects of real-life use of this drug remain unknown. This retrospective study (2012-2016) was conducted by the French Reference Center for Aplastic Anemia on patients with relapsed/refractory aplastic anemia, and patients ineligible for antithymocyte globulin or transplantation, who received eltrombopag for at least 2 months. Forty-six patients with aplastic anemia were given eltrombopag without prior antithymocyte globulin treatment (n=11) or after antithymocyte globulin administration (n=35) in a relapsed/refractory setting. Eltrombopag (median daily dose 150 mg) was introduced 17 months (range, 8-50) after the diagnosis of aplastic anemia. At last followup, 49% were still receiving treatment, 9% had stopped due to a robust response, 2% due to toxicity and 40% due to eltrombopag failure. Before eltrombopag treatment, all patients received regular transfusions. The overall rates of red blood cell and platelet transfusion independence were 7%, 33%, 46% and 46% at 1, 3, 6 months and last follow-up. Responses were slower to develop in antithymocyte treatment-naive patients. In patients achieving transfusion independence, hemoglobin concentration and platelet counts improved by 3 g/dL (interquartile range, 1.4-4.5) and 42×109/L (interquartile range, 11-100), respectively. Response in at least one lineage (according to National Institutes of Health criteria) was observed in 64% of antithymocyte treatment-naive and 74% of relapsed/refractory patients, while trilineage improvement was observed in 27% and 34%, respectively. We found high rates of hematologic improvement and transfusion independence in refractory aplastic anemia patients but also in patients ineligible for antithymocyte globulin receiving first-line treatment. In conclusion, elderly patients unfit for antithymocyte globulin therapy may benefit from eltrombopag.
Published: 2018

13. Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial

Author: Marie-Christine Kyrtsonis, Thorsten Graef, Argiris Symeonidis, Leonard T. Heffner, Miquel Granell, Veronique Leblond, Christian Buske, Elizabeth Bilotti, Priyanka Singh, Chaim Shustik, Albert Oriol, Jorge J. Castillo, Jeff Rey V Matous, Alessandra Tedeschi, Robert F. Cornell, Meletios A. Dimopoulos, Ramón García-Sanz, Steven P. Treon, Constantine S. Tam, Efstathios Kastritis, Shuo Ma, David MacDonald, Carlos Fernández de Larrea, Jianling Li, Judith Trotman, Olivier Tournilhac, Concord Repatriation General Hospital, Universitá degli Studi dell’Insubria, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Haematology Department, University Hospital of Salamanca, Hematology-Lymphoma, Laikon genarl Hospital, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Dept. of Hematology, University hospitals, National and Kapodistrian University of Athens (NKUA), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, medicine.medical_specialty, Population, Neutropenia, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, education, Adverse effect, Survival rate, ComputingMilieux_MISCELLANEOUS, Aged, Neoplasm Staging, Salvage Therapy, education.field_of_study, business.industry, Adenine, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hepatitis B, Middle Aged, medicine.disease, Prognosis, 3. Good health, Surgery, Survival Rate, Pyrimidines, Oncology, chemistry, International Prognostic Scoring System, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Ibrutinib, Pyrazoles, Rituximab, Female, Waldenstrom Macroglobulinemia, business, 030215 immunology, medicine.drug, Follow-Up Studies
Abstract: Summary Background In the era of widespread rituximab use for Waldenstrom's macroglobulinaemia, new treatment options for patients with rituximab-refractory disease are an important clinical need. Ibrutinib has induced durable responses in previously treated patients with Waldenstrom's macroglobulinaemia. We assessed the efficacy and safety of ibrutinib in a population with rituximab-refractory disease. Methods This multicentre, open-label substudy was done at 19 sites in seven countries in adults aged 18 years and older with confirmed Waldenstrom's macroglobulinaemia, refractory to rituximab and requiring treatment. Disease refractory to the last rituximab-containing therapy was defined as either relapse less than 12 months since last dose of rituximab or failure to achieve at least a minor response. Key exclusion criteria included: CNS involvement, a stroke or intracranial haemorrhage less than 12 months before enrolment, clinically significant cardiovascular disease, hepatitis B or hepatitis C viral infection, and a known bleeding disorder. Patients received oral ibrutinib 420 mg once daily until progression or unacceptable toxicity. The substudy was not prospectively powered for statistical comparisons, and as such, all the analyses are descriptive in nature. This study objectives were the proportion of patients with an overall response, progression-free survival, overall survival, haematological improvement measured by haemoglobin, time to next treatment, and patient-reported outcomes according to the Functional Assessment of Cancer Therapy-Anemia (FACT-An) and the Euro Qol 5 Dimension Questionnaire (EQ-5D-5L). All analyses were per protocol. The study is registered at ClinicalTrials.gov, number NCT02165397, and follow-up is ongoing but enrolment is complete. Findings Between Aug 18, 2014, and Feb 18, 2015, 31 patients were enrolled. Median age was 67 years (IQR 58–74); 13 (42%) of 31 patients had high-risk disease per the International Prognostic Scoring System Waldenstrom Macroglobulinaemia, median number of previous therapies was four (IQR 2–6), and all were rituximab-refractory. At a median follow-up of 18·1 months (IQR 17·5–18·9), the proportion of patients with an overall response was 28 [90%] of 31 (22 [71%] of patients had a major response), the estimated 18 month progression-free survival rate was 86% (95% CI 66–94), and the estimated 18 month overall survival rate was 97% (95% CI 79–100). Baseline median haemoglobin of 10·3 g/dL (IQR 9·3–11·7) increased to 11·4 g/dL (10·9–12·4) after 4 weeks of ibrutinib treatment and reached 12·7 g/dL (11·8–13·4) at week 49. A clinically meaningful improvement from baseline in FACT-An score, anaemia subscale score, and the EQ-5D-5L were reported at all post-baseline visits. Time to next treatment will be presented at a later date. Common grade 3 or worse adverse events included neutropenia in four patients (13%), hypertension in three patients (10%), and anaemia, thrombocytopenia, and diarrhoea in two patients each (6%). Serious adverse events occurred in ten patients (32%) and were most often infections. Five (16%) patients discontinued ibrutinib: three due to progression and two due to adverse events, while the remaining 26 [84%] of patients are continuing ibrutinib at the time of this report. Interpretation The sustained responses and median progression-free survival time, combined with a manageable toxicity profile observed with single-agent ibrutinib indicate that this chemotherapy-free approach is a potential new treatment choice for patients who had heavily pretreated, rituximab-refractory Waldenstrom's macroglobulinaemia. Funding Pharmacyclics LLC, an AbbVie Company.
Published: 2017

14. Preanalytical errors: a preliminary approach to the point of view of primary health care givers

Author: Adolfo Romero, M Carmen Barba, Isabel S. Caparrós, Juan Gómez-Salgado, Carlos Ruiz-Frutos, Margarita Reina, [Gómez-Salgado,J] Primary Care District Huelva Costa Condado Campiña, Huelva, Andalucía, Spain. [Romero,A, Caparrós,IS] Haematology Department, University Hospital Virgen de la Victoria, Málaga, Andalucía, Spain. [Barba,MC, and Reina,M] Primary Care District Málaga, Andalucía, Spain. [Ruiz-Frutos,C] Environmental Health Department, University of Huelva, Spain.
Subjects: media_common.quotation_subject, Clinical Biochemistry, Health Care::Health Care Facilities, Manpower, and Services::Health Services::Medical Errors [Medical Subject Headings], MEDLINE, Errores diagnósticos, Sample (statistics), Técnicas de laboratorio clínico, Preanalytical mistakes, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Atención primaria de salud, Humans, Diagnostic Errors, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques [Medical Subject Headings], SWOT analysis, media_common, Medical education, Teamwork, Primary Health Care, Clinical Laboratory Techniques, Biochemistry (medical), Perspective (graphical), Workload, General Medicine, Primary care, Focus group, Health Care::Health Services Administration::Patient Care Management::Comprehensive Health Care::Primary Health Care [Medical Subject Headings], Humanos, Qualitative approach, Sample collection, Psychology
Abstract: The presence of errors in the preanalytical phase is a widely studied topic. However, information regarding the perspective of those professionals involved is rather scant.Two focus groups of professionals from Primary Care involved in the preanalytical phase (general practitioners [GP], community nurses [CN], and other auxiliary health workers, including administrative personnel [AHW]) were convened. A qualitative analysis with a phenomenological approach was performed by using the structure of SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis as a guide, and results were categorized by grouping the resultant dimensions according to this structure.Overall, 12 professionals (3 GP, 6 CN, and 3 AHW) were distributed in two groups. Age and gender distribution were similar between groups. The most commented strengths were organizational capability and teamwork. The main weakness was the workload increase (compared to the short time spent on sample collection). Opportunities were related to workload optimization through on-line analytical requests. Threats were related to the long time elapsed between sample drawing at Primary Care and delivery to the Central Laboratory.The phenomenological approach allows revealing those aspects that cannot be entirely elucidated by objective data measurement. Attitudes considered as positive can be exploited by the institution, whereas those considered as negative alert us to possible future problems. Primary Care professionals offered a different point of view to laboratory staff, but both recognized high workload as the main threat and on-line analytical request as the best opportunity. These perspectives may help to improve detection and decrease the number of errors.
Published: 2015

15. Biological Description of 109 Cases of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) from the French Network of BPDCN

Author: Bernard Drenou, Sabrina Bouyer, Christophe Ferrand, Anne Galoisy, Francine Garnache Ottou, Christine Arnoulet, Blandine Bénet, Romaric Lacroix, Maïder Pagadoy, Fabrice Jardin, Marie-Christine Béné, Jean Feuillard, Philippe Saas, Chrystelle Vidal, Delphine Binda, Lydia Campos, Michel Ticchioni, Veronique Latger Cannard, Anne Roogy, Françoise Solly, Sylvie Daliphard, Elizabeth Macintyre, Maria Elena Noguera, Franck Geneviève, Françoise Schillinger, Carine Lecoq Lafon, Julien Guy, Valérie Bardet, Eric Deconinck, Anne Arnaud, Sabeha Biichle, Lucile Baseggio, Fanny Angelot Delettre, Liliana Vila, Zehaira Benseddik, Daniel Lusina, Magalie L. E. Garff Tavernier, Christophe Roumier, Véronique Salaun, Vahid Asnafi, Marie Christine Jacob, Eve Poret, Mikael Roussel, Estelle Seilles, Louis Benazet, Adriana Plesa, Veronique Harriverl, Franck Leroux, Jonchère, Laurent, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Clinical Investigation Centre, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction Générale de l'Organisation des Soins (DGOS)-Université de Bourgogne (UB), Laboratoire de Biologie Médicale, Centre hospitalier de Chartres (Chartres)-Hôpital Louis Pasteur [Chartres], Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Hématologie Cellulaire, Hospices Civils de Lyon (HCL), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hematology Laboratory, Hospices Civils de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biopathology, Haematology Department, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Immunologie, Centre Hospitalier Universitaire de Nice (CHU de Nice)-Groupe hospitalier l'Archet (Nice), Service d'hématologie biologique [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Hématologie Biologique, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Anatomie et Cytologie Pathologique B, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie - Pathologie, CHU de Saint-Étienne Hôpital Nord (Saint Etienne), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire d'hématologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Laboratoire de biologie médicale, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Ingénierie et biologie cellulaire et tissulaire (IBCT (ex IFR133)), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Service d'Hématologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Université de Franche-Comté ( UFC ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie ( CIC-P803 ), Université de Bourgogne ( UB ) -Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Centre Hospitalier Emile Muller [Mulhouse] ( CH E.Muller Mulhouse ), Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ) -Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Universitaire de Nice ( CHU de Nice ) -Groupe hospitalier l'Archet (Nice), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne-Université Paris 13 ( UP13 ), CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes], Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), CHU Angers, Vascular research center of Marseille ( VRCM ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ), Centre d'Investigation Clinique de Besançon ( CICB ), Etablissement Français du Sang Bourgogne Franche-Comté-Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Ingénierie et biologie cellulaire et tissulaire ( IBCT (ex IFR133) ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Laboratoire d'Hématologie, Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté]), Centre d'Investigation Clinique de Besançon (CICB), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang Bourgogne Franche-Comté-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Hôpital Jean Minjoz-Université de Franche-Comté (UFC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Centre Hospitalier Universitaire de Nice (CHU Nice)-Groupe hospitalier l'Archet (Nice), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: 0303 health sciences, Pathology, medicine.medical_specialty, [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Immunology, Cell Biology, Hematology, Blastic plasmacytoid dendritic cell neoplasm, Biology, Biochemistry, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Myeloid cells, medicine, Skin lesion, 030304 developmental biology, 030215 immunology
Abstract: Blastic plasmacytoid dendritic cell neoplasm is a clonal disease derived from precursors of plasmacytoid dendritic cells (pDC). It is a rare neoplasm involving the skin which may or may not be associated from the outset with a leukemic component. The disease invariably progresses to aggressive leukemic dissemination, leading to a differential diagnosis with acute leukemia. In 2004, we set up a French network to recruit biological data at diagnosis. Diagnosis was according to recommendations (Swerdlow et al, 2008), with, in addition, a mandatory panel of pDC markers (Garnache-Ottou et al, 2009) detected by flow cytometry or by immunohistochemistry on infiltrated blood, bone marrow or cutaneous lesions. In total, 109 cases of BPDCN were included in 35 hospitals (2000-2013). BPDCN is more prevalent in men (sex ratio 4.4/1) and in elderly subjects (median age: 63 years; 7 patients were Immunophenotype showed that HLA-DR and CD4 were expressed in all cases, but 4 cases did not express CD56 (confirmed using 3 different antibodies). Expression of markers of others hematopoietic lineages was frequent. Among myeloid markers, the most frequent was CD33 (46%), followed by CD117 (23%), whereas CD13, CD11c, CD15 and CD65 were rarely expressed. Monocyte markers (CD14, CD64, CD11b) and myeloperoxidase were never expressed. For the T lineage, CD2 and CD7 were the most frequent (62% and 58% respectively) whereas CD5 was rare (7%). No cytoplasmic or surface CD3 were detected. For the B lineage, CD22 was expressed in 16%, and low levels of cCD79a in 5%. Both were never expressed together, and no CD19, CD20 and immunoglobulins were found. Generally, we observed one of these antigens (Ags) per case, but in 44% of cases, there was a combination of 2 or 3 Ags from 2 or 3 different lineages. Immature Ags such as CD34 and CD133 were never found, and Tdt was found in 14% of cases. Cytogenetic analysis revealed abnormal caryotype in 65% of the 78 caryotypes evaluated, with 20 cases having a complex caryotype. The frequency of the chromosomal abnormalities involved are shown in Figure 1H. In conclusion, we describe the largest series of BPDCN to date in the literature. Detailed clinical and biological data at presentation allow improved recognition of this rare form of acute and aggressive leukemia, enabling early initiation of appropriate management. Figure 1. A: Blood cell count in 109 BPDCN patients at diagnosis. Bars represent the median. B: Typical BPDCN morphology. C: In this case, the nuclei were peripheral, cytoplasm presented heterogenous basophilia, vacuoles were rare but large pseudopodia are frequent. D: Typical morphology with frequent microvacuoles under the cytoplasmic membrane. E: Immature morphology. F: Pseudolymphocytic morphology. G: Presence of dysplasia in myeloid cells with Auer Rods in the granulocytes. The morphology of the Blastic cells is typical. H. Chromosomal abnormalities in 78 caryotypes evaluated: The histogram represents the number of cases in which each chromosome was involved (deletion, gain, translocations). Figure 1. A: Blood cell count in 109 BPDCN patients at diagnosis. Bars represent the median. B: Typical BPDCN morphology. C: In this case, the nuclei were peripheral, cytoplasm presented heterogenous basophilia, vacuoles were rare but large pseudopodia are frequent. D: Typical morphology with frequent microvacuoles under the cytoplasmic membrane. E: Immature morphology. F: Pseudolymphocytic morphology. G: Presence of dysplasia in myeloid cells with Auer Rods in the granulocytes. The morphology of the Blastic cells is typical. H. Chromosomal abnormalities in 78 caryotypes evaluated: The histogram represents the number of cases in which each chromosome was involved (deletion, gain, translocations). Disclosures Bardet: Celgene: Research Funding. Deconinck:CHUGAI: Other: Travel for international congress; PFIZER: Research Funding; ROCHE: Research Funding; NOVARTIS: Other: Travel for international congress; ALEXION: Other: Travel for international congress; JANSSEN: Other: Travel for international congress; LFB loboratory: Consultancy.
Published: 2015

16. Preanalytical errors: the professionals’ perspective

Author: José Andrés Domínguez, Adolfo Romero, Isabel S. Caparrós, Andrés Cobos, José Antonio Gómez-Fernández, Carlos Ruiz-Frutos, Juan Gómez-Salgado, [Gómez-Salgado,J] Healthcare District Huelva Costa, Condado-Campiña, Andalusian Health Service, La-Palma del Condado, Huelva, Spain. [Gómez-Salgado,J, Ruiz-Frutos,C] Department of Nursing, University of Huelva, Spain. [Romero,A, Cobos,A, Caparrós,IS] Laboratory and Haematology Department, University Hospital Virgen de la Victoria, Malaga, Spain. [Gómez-Fernández,JA] Laboratory Department, University Hospital Juan Ramón Jiménez, Huelva, Spain. [Domínguez,JA] Department of Sociology, University of Huelva, Spain., and This study was partially supported by project Fondo de Investigaciones Sanitarias (FIS) grant PIFIS 1099/12 from 'Instituto de Salud Carlos III' Ministerio de Sanidad y Política Social. Gobierno de España. (Health Ministry, Spanish Government).
Subjects: Quality Control, Actitud del personal de salud, Strengths, Attitude of Health Personnel, Clinical Biochemistry, Errores diagnósticos, Specimen Handling, Health administration, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Manejo de especímenes, Patient safety, Weakness, Qualitative analysis, Nursing, Humans, Medicine, Diagnostic Errors, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Errors [Medical Subject Headings], Technology, Industry, Agriculture::Technology, Industry, and Agriculture::Technology::Quality Control [Medical Subject Headings], business.industry, Biochemistry (medical), Perspective (graphical), Opportunity and threats (SWOT), General Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Specimen Handling [Medical Subject Headings], Control de calidad, Healthcare management, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Attitude::Attitude of Health Personnel [Medical Subject Headings], business, Preanalytical errors
Abstract: This study was aimed at understanding the perspective on preanalytical errors from the point of view of the professionals involved in the preanalytical process. A significant contribution of their specialized knowledge and experience in day-to-day practice for identifying these kinds of mistakes, and their most frequent causes, was expected.It seems evident that weaknesses and threats are closely related to institutional organization aspects and the same is true for positive elements (strengths and opportunities). There is also an important appreciation of the staff’s implication. Staff´s opinions should be taken into account by institution managers, as they offer an approach that is different and complementary to the one traditionally applied, which is purely managerial and therefore not sufficient. The results should be complemented with more updated information. Multidisciplinary cooperation must involve not only professionals from different fields but also with different roles, i.e., managers, in order to obtain results that can be used to improve healthcare, save costs and to guarantee patient’s safety. We will continue with this research line investigating the same questions among primary care staff, in order to assess “the other side of the coin” of this problem. Yes 2015-04-01
Published: 2014

17. Cytogenetic assessment of Fanconi anemia in children with aplastic anemia in Tunisia

Author: Faten, Talmoudi, Lobna, Kammoun, Nizar, Benhalim, Lamia, Torjemane, Monia, Ouederni, Lamia, Aissaoui, Amel, Lakhal, Fethi, Mellouli, Tarek B, Othmen, Mohamed, Bejaoui, Sonia, Abdelhak, Mounira, Meddeb, Koussay, Dellagi, Sondes, Hdiji, Ahlem, Amouri, S, Hmida, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Paediatric Department, Hedi Chaker Hospital [Sfax], Department of Haematology and Transplantation, National Bone Marrow Transplantation Centre, Department of Peadiatric Immuno-Haematology, National Bone Marrow Transplantation, Haematology Department, Aziza Othmana Hospital, Tunis, Centre National de Greffe de la Moëlle osseuse Tunis (CNGMO), Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory (LR11IPT05), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Laboratoire d'Immunopathologie, Vaccinologie et Génétique Moléculaire (LVGM)
Subjects: Male, Pediatrics, medicine.medical_specialty, Tunisia, Adolescent, Anemia, [SDV]Life Sciences [q-bio], Mitomycin, North africa, Consanguinity, Gastroenterology, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Fanconi anemia, Chromosome instability, Internal medicine, Chromosomal Instability, medicine, Humans, pediatric aplastic anemia, Aplastic anemia, Child, mitomycin C, 030304 developmental biology, 0303 health sciences, business.industry, Mitomycin C, Anemia, Aplastic, Infant, Chromosome Breakage, Hematology, FA siblings, medicine.disease, 3. Good health, Fanconi Anemia, Oncology, 030220 oncology & carcinogenesis, Child, Preschool, Pediatrics, Perinatology and Child Health, Cytogenetic Analysis, Female, Chromosome breakage, business
Abstract: International audience; Background:Chromosome breakage hypersensitivity to alkylating agents is the gold standard test for Fanconi anemia (FA) diagnosis. The aim of the present study was to assess the proportion of FA cases among aplastic anemia (AA) in Tunisian pediatric patients.Observation:Investigation of mitomycin C-induced chromosomal breakage was carried out in 163 pediatric patients with AA and siblings of the cases where diagnosis of FA was confirmed. We identified 31 patients with FA whose percentage of unstable mitoses ranges from 65% to 100%. Among 18 siblings who were investigated for chromosomal instability, 3 were incidentally found to be affected.Conclusions:FA is an important cause of AA in Tunisia. Our report is the first study in North Africa that explored cytogenetic and phenotypic findings in FA children. It also showed the importance of mitomycin C sensitivity screening in all FA siblings.
Published: 2013

18. Differentiation of Fanconi anemia and aplastic anemia using mitomycin C test in Tunisia

Author: Helmi Guermani, Imene Chemkhi, Lamia Aissaoui, Lamia Torjmane, Faten Talmoudi, Olfa Kilani, Nabila Abidli, Lobna Kammoun, Neila Ben Romdhane, Tarek Ben Othmane, Nizar Ben Halim, Fethi Mellouli, Wiem Ayed, Moez Elloumi, Sondes Hadiji, Yosra Ben Youssef, Sonia Abdelhak, Ahlem Amouri, Mohamed Bejaoui, Sofiene Hentati, Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory (LR11IPT05), Université de Tunis El Manar (UTM)-Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Département d'Histologie et de Cytogénétique - Institut Pasteur de Tunis, Institut Pasteur de Tunis, Department of Peadiatric Immuno-Haematology, National Bone Marrow Transplantation, Department of Haematology and Transplantation, National Bone Marrow Transplantation Centre, Haematology Department, Aziza Othmana Hospital, Tunis, Farhat Hached Hospital, Paediatric Department, Hedi Chaker Hospital [Sfax], Hôpital La Rabta [Tunis], and This work was supported by the Tunisian Ministry of Higher Education and Scientific Research (Laboratory of 'Biomedical Genomics and Oncogenetics' LR11IPT05) and the Tunisian Ministry of Public Health.
Subjects: Male, [SDV]Life Sciences [q-bio], Gastroenterology, Consanguinity, 0302 clinical medicine, Fanconi anemia, Mitomycin C, Chromosome instability, Child, 0303 health sciences, Antibiotics, Antineoplastic, Mosaicism, Anemia, Aplastic, Chromosome Breakage, General Medicine, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Child, Preschool, Female, Chromosome breakage, Aplastic anemia, General Agricultural and Biological Sciences, Adult, medicine.medical_specialty, Tunisia, Adolescent, Anemia, Mitomycin, General Biochemistry, Genetics and Molecular Biology, Diagnosis, Differential, Cytogenetics, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, 030304 developmental biology, General Immunology and Microbiology, business.industry, Chromosome Fragility, Infant, Chromosomal breakage test, medicine.disease, Fanconi Anemia, Immunology, business
Abstract: International audience; Fanconi anemia (FA) is a recessive chromosomal instability syndrome that is clinically characterized by multiple symptoms. Chromosome breakage hypersensitivity to alkylating agents is the gold standard test for FA diagnosis. In this study, we provide a detailed laboratory protocol for accurate assessment of FA diagnosis based on mitomycin C (MMC) test. Induced chromosomal breakage study was successful in 171 out of 205 aplastic anemia (AA) patients. According to the sensitivity of MMC at 50 ng/ml, 38 patients (22.22%) were diagnosed as affected and 132 patients (77.17%) as unaffected. Somatic mosaicism was suspected in an 11-year-old patient with a FA phenotype. Twenty-six siblings of FA patients were also evaluated and five of them (19.23%) were diagnosed as FA. From this study, a standard protocol for diagnosis of FA was developed. It is routinely used as a diagnostic test of FA in Tunisia.
Published: 2012

19. Dectin-1 and DC-SIGN Polymorphisms Associated with Invasive Pulmonary Aspergillosis Infection

Author: Asta Försti, Salvador Oyonarte, Carmen Belén Lupiañez, Lourdes Vazquez, Manuel Jurado, Juan Sainz, Juana Segura-Catena, Kari Hemminki, Rafael Rios, [Sainz,J, Lupiáñez,CB, Segura-Catena,J, Ríos,R, Jurado,M] Genomic Oncology Area, Genyo (Pfizer-University of Granada-Andalusian Government Centre for Genomics and Oncological Research), Granada, Spain. [Sainz,J, Hemminki,K, Försti, A] Molecular Genetic Epidemiology Department, German Cancer Research Center, Heidelberg, Germany. [Sainz,J, Jurado,M] Haematology Department, University Hospital Virgen de las Nieves, Granada,Spain. [Vazquez,L] Hematology Department, University Hospital of Salamanca, Salamanca, Spain. [Oyonarte,S] Blood Transfusion Regional Centre and Sectorial Tissue Bank, Granada, Spain. [Hemminki,K, Försti,A] Center for Primary Health Care Research, Clinical Research Center, Malmö, Sweden., and This study was supported by grants P08-CVI-4116 from Consejeríaa de Salud de la Junta de Andalucia (Sevilla, Spain) and PI081051 from Fondo de Investigaciones Sanitarias (Madrid, Spain).
Subjects: Male, Epidemiology, Enfermedades Pulmonares Fúngicas, Diseases::Bacterial Infections and Mycoses::Mycoses::Hyalohyphomycosis::Aspergillosis [Medical Subject Headings], lcsh:Medicine, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Aspergillosis, Polymerase Chain Reaction, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Mannans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Membrane Glycoproteins::Cell Adhesion Molecules [Medical Subject Headings], Genotype, Molecular Cell Biology, Odds Ratio, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Odds Ratio [Medical Subject Headings], lcsh:Science, Genetics, Multidisciplinary, Lectinas Tipo C, Fungal genetics, Fungal Diseases, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, Organisms::Eukaryota::Fungi::Mitosporic Fungi::Aspergillus::Aspergillus fumigatus [Medical Subject Headings], Infectious Diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoenzyme Techniques::Enzyme-Linked Immunosorbent Assay [Medical Subject Headings], Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings], Medicine, Female, Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface [Medical Subject Headings], Research Article, Adult, Risk, Adolescent, Phenomena and Processes::Mathematical Concepts::Probability::Risk [Medical Subject Headings], Receptores de Superficie Celular, Polimorfismo Genético, Diseases::Bacterial Infections and Mycoses::Mycoses::Lung Diseases, Fungal [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Single-nucleotide polymorphism, Enzyme-Linked Immunosorbent Assay, Receptors, Cell Surface, Biology, Polymorphism, Single Nucleotide, Molecular Genetics, Chemicals and Drugs::Carbohydrates::Polysaccharides::Mannans [Medical Subject Headings], Genetic variation, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Humans, Lectins, C-Type, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Allele, Genetic association, Aged, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide [Medical Subject Headings], Polymorphism, Genetic, Lung Diseases, Fungal, Aspergillus fumigatus, lcsh:R, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Lectins::Lectins, C-Type [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction [Medical Subject Headings], Galactose, Odds ratio, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic [Medical Subject Headings], medicine.disease, Ensayo de Inmunoadsorción Enzimática, Mananos, Aspergilosis, Check Tags::Female [Medical Subject Headings], Immunology, Reacción en Cadena de la Polimerasa, Moléculas de Adhesión Celular, lcsh:Q, Polimorfismo de Nucleótido Simple, Cell Adhesion Molecules, Population Genetics
Abstract: Journal Article; Research Support, Non-U.S. Gov't; The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1(rs3901533 T/T) and Dectin-1(rs7309123 G/G) genotypes and DC-SIGN(rs4804800 G), DC-SIGN(rs11465384 T), DC-SIGN(7248637 A) and DC-SIGN(7252229 C) alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37-22.77; OR = 4.91 95%CI 1.52-15.89; OR = 2.75 95%CI 1.27-5.95; OR = 2.70 95%CI 1.24-5.90; OR = 2.39 95%CI 1.09-5.22 and OR = 2.05 95%CI 1.00-4.22, respectively). There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1(rs3901533_T) allele and Dectin-1(rs7309123_G/G) genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1(rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk-adapted prophylaxis. Yes
Published: 2012
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20. Comprehensive investigation of genetic variation in the 8q24 region and multiple myeloma risk in the IMMEnSE consortium

Author: Krzysztof Jamroziak, Zofia Szemraj-Rogucka, Daniele Campa, Mario Petrini, Federico Canzian, Herlander Marques, Victor Moreno, Juan Sainz, Alessandro Martino, Charles Dumontet, Hartmut Goldschmidt, Anna Maria Rossi, Rafael Rios, Niels Weinhold, Federica Gemignani, Gabriele Buda, Manuel Jurado, Janusz Szemraj, Peter Bugert, Enrico Orciuolo, Fabienne Lesueur, Ramón García-Sanz, Rui Manuel Reis, Stefano Landi, Junta de Andalucía, Instituto de Salud Carlos III, Ministry of Science and Higher Education (Poland), Universidade do Minho, Department of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Oncology, Transplants and Advanced Technologies, Section of Hematology, Pisa University, Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Haematology Department, University Hospital of Salamanca, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), Medical Faculty of Mannheim, Institute of Transfusion Medicine and Immunology, Red Cross Blood Service of Baden-Württemberg-Hessen, Universität Heidelberg [Heidelberg], Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), Biomarkers and Susceptibility Unit, Catalan Institute of Oncology, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine V, National Center for Tumor Diseases (NCTD), and Scanella, Marie-Pierre
Subjects: Male, Epidemiology, Genome-wide association study, MESH: Multiple Myeloma, Myeloma, MESH: Genotype, 0302 clinical medicine, MESH: Genetic Variation, Haematological malignancies, Cancer genetics, Multiple myeloma, Cancer, Genetics, 0303 health sciences, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, Hematology, genetics, cancer genetics, cancer, epidemiology, haematological malignancies, myeloma, MESH: Case-Control Studies, 3. Good health, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, Chromosomes, Human, Pair 8, Genotype, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Genetic variation, medicine, Humans, Genetic Predisposition to Disease, Genetic variability, Gene, 030304 developmental biology, Genetic association, MESH: Humans, Science & Technology, Genetic Variation, medicine.disease, MESH: Male, Case-Control Studies, MESH: Genome-Wide Association Study, MESH: Chromosomes, Human, Pair 8, MESH: Female, Genome-Wide Association Study
Abstract: et al., Genome-wide association studies (GWAS) have shown that the 8q24 region harbours multiple independent cancer susceptibility loci, even though it is devoid of genes. Given that no GWAS data are currently available for multiple myeloma (MM), we tested the hypothesis that genetic variants in this region could play a role in MM risk. We genotyped 20 single nucleotide polymorphisms of 8q24 in 1188 MM cases and 2465 controls and found a statistically significant (P = 0·0022) association between rs2456449 and MM risk. These data provide further evidence that the genetic variability in the 8q24 region is associated with cancer risk, particularly haematological malignancies. © 2012 Blackwell Publishing Ltd., Collection of blood samples from Spain patients from Granada area and DNA extraction was partially supported by grants P08-CVI-4116 from Consejería de Salud de la Junta de Andalucia (Sevilla, Spain) and PI081051 from Fondo de Investigaciones Sanitarias (Madrid, Spain). Collection of blood samples from Polish patients and controls from Lodz area and DNA extraction was supported by a grant from Polish Ministry of Science and Higher Education (No. NN402178334).
Published: 2012

21. Bosentan and oral anticoagulants in HIV patients: what we can learn of cases reported so far

Author: Juan Enrique Martínez de la Plata, Olivia Urquízar-Rodríguez, María Angustias Molina-Arrebola, Jose Antonio Morales-Molina, [Morales-Molina, JA, Martinez-de la Plata, JE, and Urquízar-Rodríguez, O] Pharmacy Department, Hospital de Poniente, El Ejido, Almeria, Spain [Molina-Arrebola, MA] Haematology Department, Hospital de Poniente, El Ejido, Almeria, Spain
Subjects: Pediatrics, medicine.medical_specialty, Interacciones de Drogas, MEDLINE, Human immunodeficiency virus (HIV), Diseases::Virus Diseases::Sexually Transmitted Diseases::Sexually Transmitted Diseases, Viral::HIV Infections [Medical Subject Headings], Case Report, HIV patients, medicine.disease_cause, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Benzopyrans::Coumarins::4-Hydroxycoumarins::Acenocoumarol [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Pharmacological Processes::Drug Interactions [Medical Subject Headings], Medicine, Drug Interactions, Severe complication, Acenocoumarol, bosentan, lcsh:RC633-647.5, acenocoumarol, business.industry, Warfarin, VIH, Bosentan, lcsh:Diseases of the blood and blood-forming organs, drug interactions, Hematology, Warfarina, Acenocumarol, respiratory tract diseases, warfarin, Named Groups::Persons::Patients [Medical Subject Headings], Hiv patients, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Benzopyrans::Coumarins::4-Hydroxycoumarins::Warfarin [Medical Subject Headings], Hipertensión Pulmonar, business, acenocoumarol, bosentan, drug interactions, warfarin, HIV patients, medicine.drug, HIV Patients
Abstract: Journal Article; Pulmonary arterial hypertension is an infrequent but nevertheless serious life-threatening severe complication of HIV infection. It can be treated with bosentan and oral anticoagulants. Bosentan could induce the acenocoumarol metabolism and it increases the INR values. Until now, no study of interaction between bosentan and oral anticoagulants in HIV patients has reported. So we present a case of this interaction between these drugs and we reviewed MEDLINE to identify all the papers published so far. In our case, several weeks after increasing dose of bosentan acenocoumarol dose had to be progressively increased to 70 mg/week (+33%) without obtaining an adequate INR level (2.0-3.0). Forty-nine days later, we achieved a therapeutic INR with 90 mg/week of warfarin. The use of bosentan and oral anticoagulants together in these patients require a closer monitoring during first weeks of treatment, after increasing the bosentan dose and even during longer periods of time. Yes
Published: 2011

22. Risk factors for, and clinical relevance of, faecal extended-spectrum β-lactamase producing (ESBL-EC) carriage in neutropenic patients with haematological malignancies

Author: Francisco Gudiol, Jordi Carratalà, Laura Calatayud, Josefina Liñares, Carlota Gudiol, J. M. Ribera, M. Batlle, María Ángeles Domínguez, Montserrat Arnan, Hematology Department, Hospital Duran i Reynals, l'Hospitalet de Llobregat, Infectious Disease Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, University of Barcelona, REIPI (Spanish Network for Research in Infectious Diseases), Instituto de Salud Carlos III [Madrid] (ISC), Microbiology Department, Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Ciber de Enfermedades Respiratorias, ISCIII, Haematology Department, and Hospital Germans Trias I Pujol
Subjects: Male, Microbiology (medical), medicine.medical_specialty, Neutropenia, Bacteremia, Drug resistance, beta-Lactamases, Cohort Studies, Feces, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Drug Resistance, Bacterial, Epidemiology, Escherichia coli, medicine, polycyclic compounds, Humans, 030212 general & internal medicine, Risk factor, Escherichia coli Infections, 0303 health sciences, Leukemia, 030306 microbiology, business.industry, Life Sciences, General Medicine, Middle Aged, biochemical phenomena, metabolism, and nutrition, medicine.disease, bacterial infections and mycoses, 3. Good health, Molecular Typing, Transplantation, Infectious Diseases, Carriage, Hematologic Neoplasms, Carrier State, Immunology, Female, business, Cohort study
Abstract: The purpose of this study was to assess the risk factors for, and the clinical relevance of, faecal carriage by extended-spectrum β-lactamase producing Escherichia coli (ESBL-EC) in neutropenic cancer patients (NCP). An observational prospective multicentre cohort study was conducted over 2 years at two teaching hospitals. Patients with acute leukaemia or undergoing stem cell transplantation were included during neutropenia episodes. Rectal swabs were obtained at hospital admission and weekly thereafter until discharge or death. ESBL-EC colonized episodes were compared with non-colonized episodes. ESBL-EC strains were studied by PCR and isoelectric focusing, and molecular typing was performed by pulsed field gel electrophoresis (PFGE). Among 217 episodes of neutropenia, the prevalence of ESBL-EC faecal carriage was 29% (14% at hospital admission). Multivariate analysis identified previous antibiotics as the only independent risk factor for ESBL-EC faecal colonization (OR 5.38; 95% CI 2.79-10.39). Analysis of ESBL-EC isolates revealed a polyclonal distribution with CTX-M predominance (81.3%). E. coli bacteraemia was mainly caused by non-ESBL producing strains and its rate was similar in both groups (13% vs. 11%). We found no association between ESBL-EC carriage and an increased risk of ESBL-EC bacteremia or a negative influence on other clinical outcomes, including length of hospitalisation, early and overall mortality rates. ESBL-EC faecal colonization is frequent in NCP but difficult to identify by epidemiological or clinical features on presentation. Prior antibiotic therapy is the major associated risk factor. In this setting colonization does not appear to have a significant clinical relevance. Thus, routine testing for ESBL-EC faecal carriage does not seem to be beneficial.
Published: 2010

23. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study

Author: Balduini, Cl, Gugliotta, L, Luppi, Mario, Laurenti, L, Klersy, C, Pieresca, C, Quintini, G, Iuliano, F, Re, R, Spedini, P, Vianelli, N, Zaccaria, A, Pogliani, Em, Musso, R, Bobbio Pallavicini, E, Quarta, G, Galieni, P, Fragasso, A, Casella, G, Noris, P, Ascari, E, The, Italian TTP Study Group, Balduini, C, Gugliotta, L, Luppi, M, Laurenti, L, Klersy, C, Pieresca, C, Quintini, G, Iuliano, F, Re, R, Spedini, P, Vianelli, N, Zaccaria, A, Pogliani, E, Musso, R, Bobbio Pallavicini, E, Quarta, G, Galieni, P, Fragasso, A, Casella, G, Noris, P, Ascari, E, Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, Haematology, Santa Maria Nuova Hospital, Haematology, Department of Oncology, Haematology and Respiratory Diseases, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Haematology, Catholic University, A. Gemelli Hospital, Biometry and Clinical Epidemiology, Haematology-BMT, Paolo Giaccone Hospital, Giannettasio Hospital, Unit of Medicine, Civitanova Marche Hospital, Haematology and BMT, Cremona Hospital, Hematology and Oncology, L. and A. Seràgnoli Hospital, University of Bologna, Oncology, Ravenna Hospital, Haematology-BMT, San Gerardo Hospital, Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Ferrarotto University Hospital, Haematology and Oncology, Crema Hospital, A. Perrino Hospital, Mazzoni Hospital, Internal Medicine, and Madonna delle Grazie Hospital
Subjects: Adult, Male, medicine.medical_specialty, Dose, TTP, Thrombotic thrombocytopenic purpura, Anti-Inflammatory Agents, 030204 cardiovascular system & hematology, Gastroenterology, Methylprednisolone, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, MED/15 - MALATTIE DEL SANGUE, Internal medicine, Statistical significance, Medicine, Plasma exchange, Humans, Purpura, Thrombocytopenic, Idiopathic, Acute-Phase Reaction, Steroid, Survival analysis, Purpura, Thrombocytopenic, Idiopathic, Dose-Response Relationship, Drug, business.industry, Hematology, General Medicine, Middle Aged, medicine.disease, Thrombocytopenia, Survival Analysis, 3. Good health, Surgery, Treatment Outcome, 030220 oncology & carcinogenesis, Adjunctive treatment, Steroids, Female, Caplacizumab, business, medicine.drug
Abstract: International audience; Therapeutic plasma exchange (PE) is the accepted therapy for thrombotic thrombocytopenic purpura (TTP). Because not all patients achieve remission, other treatment modalities have been used in addition to PE, but no randomized clinical trial evaluated their efficacy. The aim of this multicentric study was to compare the effectiveness of standard- versus high-dose methylprednisolone as an adjunctive treatment to PE in the acute phase of TTP. Sixty patients with idiopathic TTP were randomized to receive methylprednisolone 1 mg/kg/die intravenous or 10 mg/kg/die for 3 days, thereafter, 2.5 mg/kg/die in addition to PE. Both dosages of steroids were well tolerated. At the end of induction therapy (day 23), the percentage of patients failing to achieve complete remission was significantly higher in the standard dose (16 of 30) than in the high-dose group (seven of 30). Also, the number of cases without a good response at day 9 and the number of deaths were higher in the standard-dose arm, but the differences did not reach the statistical significance. Results of present study indicate that the association of PE with high-dose instead of standard-dose steroids reduces the percentage of TTP patients that fail to achieve complete remission.
Published: 2009

24. Transcripts of ceruloplasmin but not hepcidin, both major iron metabolism genes, exhibit a decreasing pattern along the portocentral axis of mouse liver

Author: Marie-Bérengère Troadec, Bruno Turlin, André Guillouzo, Alain Fautrel, Emilie Camberlein, Bernard Drenou, Pierre Brissot, Olivier Loréal, Patricia Leroyer, Université de Rennes (UR), Haematology Department, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Department of Anatomopathology, CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Hôpital Pontchaillou, and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: Male, Iron Overload, Mouse, Iron, Ferroportin, Hepcidin, Transferrin receptor, 03 medical and health sciences, Mice, 0302 clinical medicine, Hepcidins, Liver zonation, Ploidy, Animals, Lobules of liver, RNA, Messenger, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Hemojuvelin, Laser capture microdissection, 0303 health sciences, Ploidies, biology, Life Sciences, Ceruloplasmin, Iron metabolism, Cell biology, Up-Regulation, Ferritin, Mice, Inbred C57BL, Biochemistry, Liver, 030220 oncology & carcinogenesis, biology.protein, Molecular Medicine, Gene expression, Laser microdissection, Cytometry, Antimicrobial Cationic Peptides
Abstract: Background/aims During iron overload of dietary origin, iron accumulates predominantly in periportal hepatocytes. A gradient in the basal and normal transcriptional control of genes involved in iron metabolism along the portocentral axis of liver lobules could explain this feature. Therefore, we aimed at characterizing, by quantitative RT-PCR, the expression of iron metabolism genes in adult C57BL/6 mouse hepatocytes regarding lobular localisation, with special emphasis to cell ploidy, considering its possible relationship with lobular zonation. Methods We used two methods to analyse separately periportal and perivenous liver cells: 1) a selective liver zonal destruction by digitonin prior to a classical collagenase dissociation, and 2) laser capture microdissection. We also developed a method to separate viable 4N and 8N polyploid hepatocytes by flow cytometer. Results Transcripts of ceruloplasmin, involved in iron efflux, were overexpressed in periportal areas and the result was confirmed by in situ hybridization study. By contrast, hepcidin 1, hemojuvelin, ferroportin, transferrin receptor 2, hfe and l -ferritin mRNAs were not differentially expressed according to either lobular zonation or polyploidisation level. Conclusions At variance with glutamine or urea metabolism, iron metabolism is not featured by a metabolic zonation lying only on a basal transcriptional control. The preferential periportal expression of ceruloplasmin raises the issue of its special role in iron overload disorders involving a defect in cellular iron export.
Published: 2007

25. Transdifferentiation of hepatocyte-like cells from the human hepatoma HepaRG cell line through bipotent progenitor

Author: Philippe Gripon, Bruno Turlin, Anne Corlu, Dina Kremsdorf, Serban Morosan, Bernard Drenou, Delphine Garnier, Virginie Cerec, Christiane Guguen-Guillouzo, Denise Glaise, Régulations des équilibres fonctionnels du foie normal et pathologique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogénèse des Hépatites Virales B et Immunothérapie (UMR_S 812), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Haematology Department, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pathogénèse des Hépatites Virales B et Immunothérapie ( UMR_S 812 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Emile Muller [Mulhouse] ( CH E.Muller Mulhouse ), Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ) -Groupe Hospitalier de Territoire Haute Alsace ( GHTHA ), Signalisation et Réponses aux Agents Infectieux et Chimiques ( SeRAIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: MESH: Cell Death, Pathology, MESH : Liver Neoplasms, Cell Transplantation, Cellular differentiation, Gene Expression, MESH : Hepatocytes, Mice, SCID, MESH: Hepatocytes, Mice, 0302 clinical medicine, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Liver Neoplasms, MESH : Cell Proliferation, MESH : Female, MESH: Animals, MESH: Mice, SCID, MESH: Carcinoma, Hepatocellular, 0303 health sciences, Cell Death, Transdifferentiation, Liver Neoplasms, Cell Differentiation, Cell biology, MESH: Cell Transplantation, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Liver, 030220 oncology & carcinogenesis, Neoplastic Stem Cells, Female, MESH : Cell Differentiation, MESH : Carcinoma, Hepatocellular, MESH: Cell Differentiation, medicine.medical_specialty, MESH: Gene Expression, MESH: Cell Line, Tumor, Carcinoma, Hepatocellular, MESH : Cell Lineage, Biology, Cholangiocyte, 03 medical and health sciences, MESH : Neoplastic Stem Cells, MESH: Cell Proliferation, Cell Line, Tumor, MESH : Mice, Reversible differentiation, medicine, Animals, Humans, Cell Lineage, Progenitor cell, MESH: Mice, 030304 developmental biology, Progenitor, Cell Proliferation, MESH: Humans, Hepatology, MESH : Cell Line, Tumor, MESH : Humans, MESH: Biological Markers, MESH : Liver, MESH: Cell Lineage, MESH: Neoplastic Stem Cells, MESH : Mice, SCID, MESH : Cell Transplantation, Transplantation, MESH : Biological Markers, MESH : Gene Expression, Cell culture, MESH : Cell Death, Hepatocytes, MESH : Animals, MESH: Female, Biomarkers, MESH: Liver
Abstract: International audience; Hepatic tumors, exhibiting mature hepatocytes and undifferentiated cells merging with cholangiocyte and hepatocyte phenotypes, are frequently described. The mechanisms by which they occur remain unclear. We report differentiation and transdifferentiation behaviors of human HepaRG cells isolated from a differentiated tumor developed consecutively to chronic HCV infection. We demonstrate that, in vitro, proliferating HepaRG cells differentiate toward hepatocyte-like and biliary-like cells at confluence. If hepatocyte-like cells are selectively isolated and cultured at high cell density, they proliferate and preserve their differentiation status. However, when plated at low density, they transdifferentiate into hepatocytic and biliary lineages through a bipotent progenitor. In accordance, transplantation of either undifferentiated or differentiated HepaRG cells in uPA/SCID mouse damaged liver gives rise mainly to functional human hepatocytes infiltrating mouse parenchyma. Analysis of the differentiation/transdifferentiation process reveals that: (1) the reversible differentiation fate of HepaRG cells is related to the absence of p21(CIP1) and p53 accumulation in differentiated cells; (2) HepaRG bipotent progenitors express the main markers of in vivo hepatic progenitors, and that cell differentiation process is linked to loss of their expression; (3) early and transient changes of beta-catenin localization and HNF3beta expression are correlated to Notch3 upregulation during hepatobiliary commitment of HepaRG cells. CONCLUSION: Our results demonstrate the great plasticity of transformed hepatic progenitor cells and suggest that the transdifferentiation process could supply the pool of hepatic progenitor cells. Moreover, they highlight possible mechanisms by which transdifferentiation and proliferation of unipotent hepatocytes might cooperate in the development of mixed and differentiated tumors.
Published: 2007

26. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways

Author: Nader Omidvar, Rose Ann Padua, Laura Guerenne, Stephanie Beurlet, Valérie Vanneaux, Pierre Fenaux, Fabien Guidez, Maria Elena Noguera, Mohamed Said, Laure Sarda-Mantel, Ghulam J. Mufti, Petra Gorombei, Carole Le Pogam, Pierre de la Grange, Christine Chomienne, Patricia Krief, Ken I. Mills, Marika Pla, BMC, BMC, Hémopathies Myéloïdes : Cellules Souches, Modèles Pré-Cliniques et Recherche Translationnelle (UMR 1131), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Department of Haematological Medicine, Kings College Hospital-King‘s College London, GenoSplice technology, Incubateur et Pépinière d'Entreprises Paris-Salpêtrière (iPEPS-ICM), Haematology Department, Cardiff University, Unité de Thérapie Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre for Cancer Research and Cell Biology, Queen's University [Belfast] (QUB), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Nucléaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Laboratoire d’Hématologie, Département d’Expérimentation Animale, Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), and This work was supported by grants from INSERM, Université Paris Diderot,Fondation de France, Association pour la Recherche Contre sur le Cancer,Association Laurette Fugain, Ligue Contre le Cancer. FP7 Marie Curie N° N°264361
Subjects: 0301 basic medicine, Cancer Research, [SDV]Life Sciences [q-bio], Bioinformatics, Mice, Risk Factors, hemic and lymphatic diseases, MDS, Oligonucleotide Array Sequence Analysis, Regulation of gene expression, Hematology, Reverse Transcriptase Polymerase Chain Reaction, Wnt signaling pathway, Myeloid leukemia, lcsh:Diseases of the blood and blood-forming organs, Cell cycle, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Gene Expression Regulation, Neoplastic, [SDV] Life Sciences [q-bio], Leukemia, Oncology, Leukemia, Myeloid, Acute Disease, Mice models, Signal Transduction, medicine.medical_specialty, Mice, Transgenic, lcsh:RC254-282, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Animals, Humans, Molecular Biology, business.industry, lcsh:RC633-647.5, Myelodysplastic syndromes, Research, Gene Expression Profiling, Reproducibility of Results, Gene expression profile, medicine.disease, Gene expression profiling, Disease Models, Animal, 030104 developmental biology, Myelodysplastic Syndromes, Cancer research, business, Myelodysplastic syndrome
Abstract: Background In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. Methods We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Results Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. Conclusions These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0235-8) contains supplementary material, which is available to authorized users.
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27. Outcomes with single-agent gilteritinib for relapsed or refractory FLT3-mutant AML after contemporary induction therapy.

Author: Othman J, Hwang A, Brodermann M, Abdallah I, McCloskey K, Gallipoli P, Clarke G, Dang R, Vidler J, Krishnamurthy P, Basheer F, Latif AL, Palanicawandar R, Taylor T, Khan A, Campbell V, Hogan F, Kanellopoulos A, Fleming K, Collins A, Dalley C, Loke J, Marshall S, Taussig D, Munisamy S, Loizou E, Yassin H, Dennis M, Zhao R, Belsham E, Murray D, Fowler N, O'Nions J, Khan A, Sellar R, and Dillon R
Subjects: Humans, Middle Aged, Male, Female, Aged, Adult, Treatment Outcome, Aged, 80 and over, Induction Chemotherapy, Protein Kinase Inhibitors therapeutic use, Recurrence, Drug Resistance, Neoplasm, fms-Like Tyrosine Kinase 3 genetics, fms-Like Tyrosine Kinase 3 antagonists & inhibitors, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, Pyrazines therapeutic use, Aniline Compounds therapeutic use, Mutation
Abstract: Abstract: Gilteritinib is the current standard of care for relapsed or refractory fms related receptor tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia in many countries, however outcomes for patients relapsing after contemporary first-line therapies (intensive chemotherapy with midostaurin, or nonintensive chemotherapy with venetoclax) are uncertain. Moreover, reported data on toxicity and health care resource use is limited. Here, we describe a large real-world cohort of 152 patients receiving single-agent gilteritinib in 38 UK hospitals. Median age was 61 years, and 36% had received ≥2 prior lines of therapy, including a FLT3 inhibitor in 41% and venetoclax in 24%. A median of 4 cycles of gilteritinib were administered, with 56% of patients requiring hospitalization in the first cycle (median, 10 days). Over half of patients required transfusion in each of the first 4 cycles. Complete remission (CR) was achieved in 21%, and CR with incomplete recovery (CRi) in a further 9%. Remission rates were lower for patients with FLT3-tyrosine kinase domain or adverse karyotype. Day-30 and day-60 mortality were 1% and 10.6%, respectively, and median overall survival was 9.5 months. On multivariable analysis, increasing age, KMT2A rearrangement, and complex karyotype were associated with worse survival whereas RUNX1 mutations were associated with improved survival. Twenty patients received gilteritinib as first salvage having progressed after first-line therapy with venetoclax, with CR/CRi achieved in 25% and median survival 4.5 months. Real-world results with gilteritinib mirror those seen in the clinical trials, but outcomes remain suboptimal, with more effective strategies needed., (© 2024 by The American Society of Hematology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)
Published: 2024
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28. NK- and T-cell repertoire is established early after allogeneic HSCT and is imprinted by CMV reactivation.

Author: Schäfer A, Calderin Sollet Z, Hervé MP, Buhler S, Ferrari-Lacraz S, Norman PJ, Kichula KM, Farias TDJ, Masouridi-Levrat S, Mamez AC, Pradier A, Simonetta F, Chalandon Y, and Villard J
Subjects: Humans, Adult, Male, Female, Middle Aged, Transplantation, Homologous, Receptors, Antigen, T-Cell metabolism, Young Adult, Aged, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Hematopoietic Stem Cell Transplantation adverse effects, Cytomegalovirus immunology, Cytomegalovirus Infections immunology, T-Lymphocytes immunology, T-Lymphocytes metabolism, Virus Activation immunology
Abstract: Abstract: Besides genetic influences, nongenetic factors such as graft-versus-host disease and viral infections have been shown to be important shapers of the immune reconstitution and diversification processes after hematopoietic stem cell transplantation (HSCT). However, differential susceptibility to immune modulation by nongenetic factors is not fully understood. We determined to follow the reconstitution of the T-cell receptor (TCR) repertoire through immune sequencing of natural killer (NK) cells using a 35-marker spectral flow cytometry panel and in relation to clinical events. A longitudinal investigation was performed on samples derived from 54 HSCT recipients during the first year after HSCT. We confirmed a significant contraction in TCR repertoire diversity, with remarkable stability over time. Cytomegalovirus (CMV) reactivation had the ability to significantly change TCR repertoire clonality and composition, with a long-lasting imprint. Our data further revealed skewing of NK-cell reconstitution in CMV reactivated recipients, with an increased frequency of KIR2DL2L3S2+ adaptive, cytolytic, and functional CD107a+ NK cells, concomitant with a reduced pool of NKG2A+ NK cells. We provided support that CMV might act as an important driver of peripheral homeostatic proliferation of circulating specific T and NK cells, which can be viewed as a compensatory mechanism to establish a new peripheral repertoire., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Published: 2024
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29. Data-driven, harmonised classification system for myelodysplastic syndromes: a consensus paper from the International Consortium for Myelodysplastic Syndromes.

Author: Komrokji RS, Lanino L, Ball S, Bewersdorf JP, Marchetti M, Maggioni G, Travaglino E, Al Ali NH, Fenaux P, Platzbecker U, Santini V, Diez-Campelo M, Singh A, Jain AG, Aguirre LE, Tinsley-Vance SM, Schwabkey ZI, Chan O, Xie Z, Brunner AM, Kuykendall AT, Bennett JM, Buckstein R, Bejar R, Carraway HE, DeZern AE, Griffiths EA, Halene S, Hasserjian RP, Lancet J, List AF, Loghavi S, Odenike O, Padron E, Patnaik MM, Roboz GJ, Stahl M, Sekeres MA, Steensma DP, Savona MR, Taylor J, Xu ML, Sweet K, Sallman DA, Nimer SD, Hourigan CS, Wei AH, Sauta E, D'Amico S, Asti G, Castellani G, Delleani M, Campagna A, Borate UM, Sanz G, Efficace F, Gore SD, Kim TK, Daver N, Garcia-Manero G, Rozman M, Orfao A, Wang SA, Foucar MK, Germing U, Haferlach T, Scheinberg P, Miyazaki Y, Iastrebner M, Kulasekararaj A, Cluzeau T, Kordasti S, van de Loosdrecht AA, Ades L, Zeidan AM, and Della Porta MG
Subjects: Humans, Consensus, Myelodysplastic Syndromes classification, Myelodysplastic Syndromes diagnosis, Myelodysplastic Syndromes genetics
Abstract: The WHO and International Consensus Classification 2022 classifications of myelodysplastic syndromes enhance diagnostic precision and refine decision-making processes in these diseases. However, some discrepancies still exist and potentially cause inconsistency in their adoption in a clinical setting. We adopted a data-driven approach to provide a harmonisation between these two classification systems. We investigated the importance of genomic features and their effect on the cluster assignment process to define harmonised entity labels. A panel of expert haematologists, haematopathologists, and data scientists who are members of the International Consortium for Myelodysplastic Syndromes was formed and a modified Delphi consensus process was adopted to harmonise morphologically defined categories without a distinct genomic profile. The panel held regular online meetings and participated in a two-round survey using an online voting tool. We identified nine clusters with distinct genomic features. The cluster of highest hierarchical importance was characterised by biallelic TP53 inactivation. Cluster assignment was irrespective of blast count. Individuals with monoallelic TP53 inactivation were assigned to other clusters. Hierarchically, the second most important group included myelodysplastic syndromes with del(5q). Isolated del(5q) and less than 5% of blast cells in the bone marrow were the most relevant label-defining features. The third most important cluster included myelodysplastic syndromes with mutated SF3B1. The absence of isolated del(5q), del(7q)/-7, abn3q26.2, complex karyotype, RUNX1 mutations, or biallelic TP53 were the basis for a harmonised label of this category. Morphologically defined myelodysplastic syndrome entities showed large genomic heterogeneity that was not efficiently captured by single-lineage versus multilineage dysplasia, marrow blasts, hypocellularity, or fibrosis. We investigated the biological continuum between myelodysplastic syndromes with more than 10% bone marrow blasts and acute myeloid leukaemia, and found only a partial overlap in genetic features. After the survey, myelodysplastic syndromes with low blasts (ie, less than 5%) and myelodysplastic syndromes with increased blasts (ie, 5% or more) were recognised as disease entities. Our data-driven approach can efficiently harmonise current classifications of myelodysplastic syndromes and provide a reference for patient management in a real-world setting., Competing Interests: Declaration of interests UG reports speaker honoraria from Novartis, AbbVie, and BMS; and institutional research support from BMS, AbbVie, and Jazz Pharmaceuticals. FE reports consultancy or advisory roles for AbbVie, Incyte, Syros, Novartis, and Jazz Pharmaceuticals. SH reports research support from STORM Therapeutics and AstraZeneca. EAG reports honoraria from AAMDS, MedscapeLIVE!, MediCom Worldwide, MJH Life Sciences, ASH, MDS International Foundation, and Physicians’ Education Resource; consulting fees from AbbVie, Alexion, Apellis, Takeda Oncology, Astex/Taiho Oncology, Alexion/AstraZeneca Rare Disease, Celgene/BMS, CTI BioPharma, Novartis, Partner Therapeutics, Picnic Health, and Servier; and research funding from Alexion, Apellis, Astex /Otsuka/Taiho Oncology, Blueprint Medicines, Celldex Therapeutics, Genentech, and NextCure. MAS reports participation on advisory boards for BMS, Kurome, Schrödinger, and Karyopharm. MD-C reports participation on a data safety monitoring board or advisory board for BMS, Novartis, Blueprint Medicines, GSK, Agios, Hemavan, Syros, Keros, Curis, and Astex/Otsuka; and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events for BMS, Novartis, and Keros. UP reports research support and honoraria from BMS, Geron, Curis, AbbVie, and Janssen. RBe reports employment or equity from Aptose Biosciences; participation on advisory boards for BMS, Servier, NeoGenomics, and Geron; being Data Monitoring Committee Chair for Gilead, Ipsen, and Keros; and consultancy for TenSixteen. YM reports honoraria from Nippon Shinyaku, BMS, Novartis, Sumitomo Pharma, Kyowa Kirin, AbbVie, Daiichi Sankyo, Takeda, Janssen, Astellas, Pfizer, Eisai, and Otsuka; and research funding from Chugai. AED reports participation on advisory boards, consultancy, or honoraria from Celgene/BMS, Agios, Novartis, Astellas, and Gilead; and participation on clinical trial committees or data safety monitoring boards for Novartis, AbbVie, Kura, Geron, Servier, Keros, and Celgene/BMS. DPS reports employment by Ajax Therapeutics; former employment by Novartis; and minor equity in Arrowhead and Bluebird. TKK reports consultancy for Agenus and ImmunoBiome. AK reports research support from Novartis and BMS; consulting fees from Alexion, Novartis, Amgen, Agios, Pfizer, Samsung, Celgene, F Hoffmann-La Roche, and Sobi; honoraria from Alexion, Novartis, Pfizer, Amgen, Samsung, Celgene, F Hoffmann-La Roche, BMS, Sobi, and Silence Therapeutics; and speakers fees from Alexion, Novartis, Amgen, Pfizer, Celgene, F Hoffmann-La Roche, and Sobi. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
Published: 2024
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30. A Cost-Effectiveness Analysis of Axicabtagene Ciloleucel versus Tisagenlecleucel in the Treatment of Diffuse Large B-cell Lymphoma Based on a Real-World French Registry.

Author: Ray M, Castaigne JG, Zang A, Patel A, Hancock E, Brighton N, and Bachy E
Subjects: Humans, Male, France, Middle Aged, Female, Aged, Antigens, CD19 therapeutic use, Antigens, CD19 economics, Antigens, CD19 immunology, Adult, Receptors, Antigen, T-Cell therapeutic use, Cost-Effectiveness Analysis, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Large B-Cell, Diffuse economics, Cost-Benefit Analysis, Registries, Biological Products therapeutic use, Biological Products economics, Immunotherapy, Adoptive economics, Immunotherapy, Adoptive methods, Immunotherapy, Adoptive adverse effects
Abstract: Introduction: Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are chimeric antigen receptor T-cell therapies that were evaluated in third and later line (3L+) relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the ZUMA-1 and JULIET trials, respectively. As of October 2021, the DESCAR-T registry included 729 French patients with 3L+ r/r DLBCL who received axi-cel or tisa-cel. Using these data, propensity score matching was used to conduct an adjusted comparison between axi-cel and tisa-cel. Axi-cel was associated with statistically significant improvements in overall survival (OS) and progression-free survival (PFS), and significantly more frequent Grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS), compared with tisa-cel. There was no significant difference in Grade ≥ 3 cytokine release syndrome (CRS). The current analysis assessed the cost-effectiveness of axi-cel versus tisa-cel in the treatment of 3L+ r/r DLBCL using propensity score-matched data from the DESCAR-T registry., Methods: A partitioned survival model was used to extrapolate costs and quality-adjusted life years (QALYs) over a lifetime. Survival curves for PFS and OS were based on independent mixture cure models fitted to digitized Kaplan-Meier data for the propensity score-matched DESCAR-T populations. Average duration of intensive care unit stays for each of axi-cel and tisa-cel in DESCAR-T were used to inform adverse event costs. Selected parametric survival distributions were based on clinical expert validation. Utility values were derived from ZUMA-1, and costs were obtained from French registries and published sources. List prices were used for both axi-cel and tisa-cel. Costs and outcomes were discounted at an annual rate of 2.5%., Results: Axi-cel is associated with an incremental cost-effectiveness ratio of €15,520 per QALY compared with tisa-cel., Conclusion: Based on explicit willingness-to-pay thresholds applied in Europe, axi-cel is expected to be a cost-effective use of healthcare resources in real-world clinical settings compared with tisa-cel in 3L+ r/r DLBCL., (© 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.)
Published: 2024
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31. Tissue factor pathway inhibitor - cofactor-dependent regulation of the initiation of coagulation.

Author: Ahnström J, Petri A, and Crawley JTB
Subjects: Humans, Protein S metabolism, Protein Isoforms metabolism, Thrombosis metabolism, Hemorrhage metabolism, Lipoproteins metabolism, Blood Coagulation
Abstract: Purpose of Review: In humans, tissue factor pathway inhibitor (TFPI) exists in two alternatively spliced isoforms, TFPIα and TFPIβ. TFPIα consists of three Kunitz domains (K1, K2 and K3) and a highly basic C-terminal tail. K1 inhibits the tissue factor-activated factor VII complex, K2 specifically inhibits activated factor X, K3 is essential for interaction with its cofactor, protein S, and the basic C-terminus is binds factor V-short (FV-short) with high affinity. TFPIβ consists of K1 and K2 that is glycosylphosphatidylinositol anchored directly to cell surfaces. This review explores the structure/function of TFPI and its cofactors (protein S and FV-short), and the relative contributions that different TFPI isoforms may play in haemostatic control., Recent Findings: Recent data have underscored the importance of TFPIα function and its reliance on its cofactors, protein S and FV-short, in influencing haemostatic control as well as bleeding and thrombotic risk., Summary: TFPIα is likely the most important pool of TFPI in modifying the risk of thrombosis and bleeding. TFPIα forms a trimolecular complex with FV-short and protein S in plasma. FV-short expression levels control the circulating levels of TFPIα, whereas protein S exerts essential cofactor mediated augmentation of it anticoagulant function., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
Published: 2024
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32. Small-volume blood sample collection tubes in adult intensive care units: A rapid practice guideline.

Author: Callum J, Putowski Z, Alhazzani W, Belley-Cote E, Møller MH, Curry N, Al Duhailib Z, Fung M, Giocobbo L, Granholm A, Louw V, Maybohm P, Muller M, Nielsen N, Oleschuk C, Raza S, Scruth E, Siegal D, Stanworth SJ, Vlaar APJ, White M, and Oczkowski S
Subjects: Humans, Adult, Critical Care methods, Intensive Care Units, Blood Specimen Collection methods
Abstract: Background: This Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) provides an evidence-based recommendation to address the question: in adult patients in intensive care units (ICUs), should we use small-volume or conventional blood collection tubes?, Methods: We included 23 panelists in 8 countries and assessed and managed financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. We conducted a systematic review, including evidence from observational and randomized studies. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework., Results: We identified 8 studies (1 cluster and 2 patient-level randomized trials; 5 observational studies) comparing small-volume to conventional tubes. We had high certainty evidence that small-volume tubes reduce daily and cumulative blood sampling volume; and moderate certainty evidence that they reduce the risk of transfusion and mean number of red blood cell units transfused, but these estimates were limited by imprecision. We had high certainty that small-volume tubes have a similar rate of specimens with insufficient quantity. The panel considered that the desirable effects of small-volume tubes outweigh the undesirable effects, are less wasteful of resources, and are feasible, as demonstrated by successful implementation across multiple countries, although there are upfront implementation costs to validate small-volume tubes on laboratory instrumentation., Conclusion: This ICM-RPG panel made a strong recommendation for the use of small-volume sample collection tubes in adult ICUs based on overall moderate certainty evidence., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)
Published: 2024
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33. Where hematology meets rheumatology-VEXAS syndrome.

Author: Oun H, Gordon W, Leach M, and Bain BJ
Subjects: Humans, Myelodysplastic Syndromes, Skin Diseases, Genetic
Published: 2024
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34. Erythrocyte deformability correlates with systemic inflammation.

Author: Jacob C, Piyasundara L, Bonello M, Nathan M, Kaninia S, Varatharaj A, Roy N, and Galea I
Subjects: Humans, Male, Female, Middle Aged, Adult, Prospective Studies, Aged, Biomarkers blood, Erythrocytes metabolism, Erythrocytes pathology, Linear Models, Erythrocyte Deformability, Inflammation blood, C-Reactive Protein analysis
Abstract: Recent evidence suggests that systemic conditions, particularly those associated with inflammation, can affect erythrocyte deformability in the absence of haematological conditions. In this exploratory study, we investigated the relationship between systemic inflammatory status and erythrocyte deformability (using osmotic gradient ektacytometry) in a heterogenous study population consisting of individuals with no medical concerns, chronic conditions, and acute illness, providing a wide range of systemic inflammation severity. 22 participants were included in a prospective observational study. Maximum Elongation Index (EI max ) in ektacytometry served as the readout for erythrocyte deformability. Inflammatory status was assessed using C-reactive protein (CRP) and self-reported symptoms associated with inflammatory activation (Sickness Questionnaire Scores, SicknessQ). In a univariate linear regression, both CRP and SicknessQ scores significantly predicted EI max (CRP: F(1,20) = 7.751, p < 0.05 (0.011), R 2 = 0.279; SicknessQ: F(1,18) = 4.831, p < 0.05 (0.041), R 2 = 0.212). Sensitivity analyses with multivariable linear regression correcting for age showed concordant findings. Results suggest a linear relationship between erythrocyte deformability and biochemical and clinical markers of systemic inflammation. Replication of findings in a larger study, and mechanisms and clinical consequences need further in investigation., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest relevant to this work., (Copyright © 2024. Published by Elsevier Inc.)
Published: 2024
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35. Pleiotropic Effects of Heparin and its Monitoring in the Clinical Practice.

Author: Arachchillage DJ and Kitchen S
Subjects: Humans, Heparin, Low-Molecular-Weight therapeutic use, Heparin, Low-Molecular-Weight pharmacology, Drug Monitoring methods, Heparin therapeutic use, Heparin pharmacology, Anticoagulants therapeutic use, Anticoagulants pharmacology, Anticoagulants pharmacokinetics
Abstract: Unfractionated heparin (UFH) was uncovered in 1916, has been used as an anticoagulant since 1935, and has been listed in the World Health Organization's Model List of Essential Medicines. Despite the availability of many other anticoagulants, the use of heparin (either low molecular weight heparin [LMWH] or UFH) is still substantial. Heparin has pleotropic effects including anticoagulant and several nonanticoagulant properties such as antiproliferative, anti-inflammatory activity, and anticomplement effects. Although UFH has been widely replaced by LMWH, UFH is still the preferred anticoagulant of choice for patients undergoing cardiopulmonary bypass surgery, extracorporeal membrane oxygenation, and patients with high-risk mechanical cardiac valves requiring temporary bridging with a parenteral anticoagulant. UFH is a highly negatively charged molecule and binds many positively charged molecules, hence has unpredictable pharmacokinetics, and variable anticoagulant effect on an individual patient basis. Therefore, anticoagulant effects of UFH may not be proportional to the dose of UFH given to any individual patient. In this review, we discuss the anticoagulant and nonanticoagulant activities of UFH, differences between UFH and LMWH, when to use UFH, different methods of monitoring the anticoagulant effects of UFH (including activated partial thromboplastin time, heparin anti-Xa activity level, and activated clotting time), while discussing pros and cons related to each method and comparison of clinical outcomes in patients treated with UFH monitored with different methods based on available evidence., Competing Interests: D.J.A. received speaker fees and registration fees for national scientific conference from Werfen. S.K. received consultancy fees from Werfen and Roche., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)
Published: 2024
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36. Cardiac infiltration in Langerhans cell histiocytosis.

Author: Lwin MT, Giannoudi M, Sengupta A, Griffin M, and Plein S
Abstract: Competing Interests: Conflict of interest: The authors have no conflicts of interest to declare.
Published: 2024
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37. Lupus anticoagulant and valvular cardiac surgery.

Author: Kamath PBRD, Braham DL, Arachchillage DJ, and Loja D
Abstract: Despite its name, lupus anticoagulant (LAC) neither exclusively occurs in lupus nor induces anticoagulation. It is an antiphospholipid antibody found in 2%-4% of the population that promotes clot formation by targeting phospholipid-protein complexes in cell membranes. However, in vitro, LAC exhibits paradoxical effects, prolonging clotting times in phospholipid-dependent assays such as Activated Partial Thromboplastin Time (APTT). This unpredictability extends to point-of-care tests like Activated Clotting Time (ACT), which are frequently used to monitor anticoagulation during cardiac surgeries involving cardiopulmonary bypass (CPB). High doses of unfractionated heparin (UFH) are administered in these procedures, but the presence of LAC complicates ACT measurements, creating challenges for both anesthesiologists and surgeons. This case report highlights the clinical implications of LAC in perioperative management, underscoring the difficulties in ensuring adequate anticoagulation during CPB., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Published: 2024
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38. Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy.

Author: Lei T, Wang Y, Zhang Y, Yang Y, Cao J, Huang J, Chen J, Chen H, Zhang J, Wang L, Xu X, Gale RP, and Wang L
Abstract: Chimeric Antigen Receptor (CAR)-T-cell therapy has revolutionized cancer immune therapy. However, challenges remain including increasing efficacy, reducing adverse events and increasing accessibility. Use of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology can effectively perform various functions such as precise integration, multi-gene editing, and genome-wide functional regulation. Additionally, CRISPR screening using large-scale guide RNA (gRNA) genetic perturbation provides an unbiased approach to understanding mechanisms underlying anti-cancer efficacy of CAR T-cells. Several emerging CRISPR tools with high specificity, controllability and efficiency are useful to modify CAR T-cells and identify new targets. In this review we summarize potential uses of the CRISPR system to improve results of CAR T-cells therapy including optimizing efficacy and safety and, developing universal CAR T-cells. We discuss challenges facing CRISPR gene editing and propose solutions highlighting future research directions in CAR T-cell therapy., (© 2024. The Author(s).)
Published: 2024
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39. Proposals for revised International Working Group-European LeukemiaNet criteria for anemia response in myelofibrosis.

Author: Tefferi A, Barosi G, Passamonti F, Hernandez-Boluda JC, Bose P, Döhner K, Ellis M, Gangat N, Garcia JS, Gisslinger H, Gotlib J, Guglielmelli P, Gupta V, Harrison C, Hexner EO, Hobbs GS, Kiladjian JJ, Koschmieder S, Kroger N, Kuykendall AT, Loscocco GG, Mascarenhas J, Masarova L, Mesa R, Mora B, Odenike O, Oh ST, Pardanani A, Patel A, Pemmaraju N, Rambaldi A, Rampal R, Sirhan S, Szuber N, Talpaz M, Vachhani PJ, Vannucchi AM, and Barbui T
Subjects: Humans, Female, Male, Hemoglobins analysis, Europe, Blood Transfusion, Primary Myelofibrosis diagnosis, Primary Myelofibrosis therapy, Primary Myelofibrosis blood, Anemia diagnosis, Anemia therapy, Anemia etiology, Anemia blood
Abstract: Abstract: With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate interstudy comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group-European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to (1) account for gender-specific differences in determining hemoglobin levels for eligibility criteria; (2) revise the definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices; and (3) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks before study enrollment) and hemoglobin thresholds for eligibility criteria (<10 g/dL for women and <11 g/dL for men). The revised document also provides separate (TDA vs non-TDA) and graded (major vs minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment., (© 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.)
Published: 2024
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40. In situ visualization of endothelial cell-derived extracellular vesicle formation in steady state and malignant conditions.

Author: Atkin-Smith GK, Santavanond JP, Light A, Rimes JS, Samson AL, Er J, Liu J, Johnson DN, Le Page M, Rajasekhar P, Yip RKH, Geoghegan ND, Rogers KL, Chang C, Bryant VL, Margetts M, Keightley MC, Kilpatrick TJ, Binder MD, Tran S, Lee EF, Fairlie WD, Ozkocak DC, Wei AH, Hawkins ED, and Poon IKH
Subjects: Animals, Mice, Bone Marrow metabolism, Humans, Intravital Microscopy methods, Phosphatidylserines metabolism, Mitochondria metabolism, Male, Female, Extracellular Vesicles metabolism, Endothelial Cells metabolism, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute pathology, Mice, Inbred C57BL
Abstract: Endothelial cells are integral components of all vasculature within complex organisms. As they line the blood vessel wall, endothelial cells are constantly exposed to a variety of molecular factors and shear force that can induce cellular damage and stress. However, how endothelial cells are removed or eliminate unwanted cellular contents, remains unclear. The generation of large extracellular vesicles (EVs) has emerged as a key mechanism for the removal of cellular waste from cells that are dying or stressed. Here, we used intravital microscopy of the bone marrow to directly measure the kinetics of EV formation from endothelial cells in vivo under homoeostatic and malignant conditions. These large EVs are mitochondria-rich, expose the 'eat me' signal phosphatidylserine, and can interact with immune cell populations as a potential clearance mechanism. Elevated levels of circulating EVs correlates with degradation of the bone marrow vasculature caused by acute myeloid leukaemia. Together, our study provides in vivo spatio-temporal characterization of EV formation in the murine vasculature and suggests that circulating, large endothelial cell-derived EVs can provide a snapshot of vascular damage at distal sites., (© 2024. The Author(s).)
Published: 2024
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41. Acute Myeloid Leukaemia With Morphologic and Immunophenotypic Differentiation to Acute Erythroid Leukaemia at the Time of Relapse.

Author: Liston K and Mykytiv V
Published: 2024
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42. Cyclophosphamide-free Mobilisation Increases Safety While Preserving the Efficacy of Autologous Haematopoietic Stem Cell Transplantation in Refractory Crohn's Disease Patients.

Author: Giordano A, Rovira M, Veny M, Barastegui R, Marín P, Martínez C, Fernández-Avilés F, Suárez-Lledó M, Domènech A, Serrahima A, Lozano M, Cid J, Ordás I, Fernández-Clotet A, Caballol B, Gallego M, Vara A, Masamunt MC, Giner À, Teubel I, Esteller M, Corraliza AM, Panés J, Salas A, and Ricart E
Subjects: Humans, Female, Male, Adult, Prospective Studies, Middle Aged, Benzylamines, Cyclams, Granulocyte Colony-Stimulating Factor administration & dosage, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Transplantation Conditioning methods, Immunosuppressive Agents therapeutic use, Heterocyclic Compounds administration & dosage, Heterocyclic Compounds therapeutic use, Young Adult, Treatment Outcome, Crohn Disease therapy, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Mobilization methods, Transplantation, Autologous methods
Abstract: Background and Aim: Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for refractory Crohn's disease [CD]. However, high adverse event rates related to chemotherapy toxicity and immunosuppression limit its applicability. This study aims to evaluate AHSCT's safety and efficacy using a cyclophosphamide [Cy]-free mobilisation regimen., Methods: A prospective, observational study included 14 refractory CD patients undergoing AHSCT between June 2017 and October 2022. The protocol involved outpatient mobilisation with G-CSF 12-16 μg/kg/daily for 5 days, and optional Plerixafor 240 μg/d [1-2 doses] if the CD34 + cell count target was unmet. Standard conditioning with Cy and anti-thymocyte globulin was administered. Clinical, endoscopic, and radiological assessments were conducted at baseline and during follow-up., Results: All patients achieved successful outpatient mobilisation [seven patients needed Plerixafor] and underwent transplantation. Median follow-up was 106 weeks (interquartile range [IQR] 52-348). No mobilisation-related serious adverse events [SAEs] or CD worsening occurred. Clinical and endoscopic remission rates were 71% and 41.7% at 26 weeks, 64% and 25% at 52 weeks, and 71% and 16.7% at the last follow-up, respectively. The percentage of patients who restarted CD therapy for clinical relapse and/or endoscopic/radiological activity was 14% at 26 weeks, 57% at 52 weeks, and 86% at the last follow-up, respectively. Peripheral blood cell populations and antibody levels post-AHSCT were comparable to Cy-based mobilisation., Conclusions: Cy-free mobilisation is safe and feasible in refractory CD patients undergoing AHSCT. Although relapse occurs in a significant proportion of patients, clinical and endoscopic responses are achieved upon CD-specific therapy reintroduction., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Published: 2024
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43. Pericardial Disease in Patients with Cancer: Clinical Insights on Diagnosis and Treatment.

Author: Lorenzo-Esteller L, Ramos-Polo R, Pons Riverola A, Morillas H, Berdejo J, Pernas S, Pomares H, Asiain L, Garay A, Martínez Pérez E, Jiménez-Marrero S, Alcoberro L, Nadal E, Gubern-Prieto P, Gual-Capllonch F, Hidalgo E, Enjuanes C, Comin-Colet J, and Moliner P
Abstract: Pericardial disease is increasingly recognized in cancer patients, including acute pericarditis, pericardial effusion, and constrictive pericarditis, often indicating a poor prognosis. Acute pericarditis arises from direct tumor involvement, cancer therapies, and radiotherapy. Immune checkpoint inhibitor (ICI)-related pericarditis, though rare, entails significant mortality risk. Treatment includes NSAIDs, colchicine, and corticosteroids or anti-IL1 drugs in refractory cases. Pericardial effusion is the most frequent manifestation, primarily caused by lung cancer, followed by breast cancer, lymphoma, leukemia, gastrointestinal tumors, and melanoma. Chemotherapy, immunotherapy, and radiotherapy may also cause fluid accumulation in the pericardial space. Symptomatic relief for pericardial effusion may require pericardiocentesis, prolonged catheter drainage, or a pericardial window. Instillation of intrapericardial cytostatic agents may reduce recurrence. Constrictive pericarditis, though less common, often develops from radiotherapy and requires multimodality imaging for diagnosis, with pericardiectomy as the definitive treatment. Primary pericardial tumors are rare, with metastases being more frequent. Patients with cancer and pericardial disease generally have poor survival, emphasizing the need for early detection. A multidisciplinary approach involving hematologists, oncologists, and cardiologists is crucial to tailoring pericardial disease treatment to a patient's clinical status, thereby improving the quality of life and prognosis.
Published: 2024
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44. The Importance of Real-World Data in Evaluating the Safety of Biosimilars: A Descriptive Study of Clinical Practice in an Oncohematological Italian Population.

Author: Urru SAM, Mayer F, Spila Alegiani S, Paoloni F, Guella A, Murru R, Bucaneve G, Formoso G, Racanelli V, Ferrarini I, Fozza C, Longo G, Musicco F, and Campomori A
Abstract: The clinical safety and efficacy of rituximab biosimilars compared to the reference rituximab (Mabthera) have been well established in randomized trials. However, concerns persist regarding the safety of changing from the reference product to biosimilars, and particularly between different biosimilars. This prospective multicenter observational study was conducted in 13 oncohematology units of eight Italian regions. The study included 800 patients with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) who received rituximab between March 2018 and June 2022. To minimize survivorship bias, only newly diagnosed patients (i.e., those without prior rituximab treatment) were included in the analysis of adverse drug reactions (ADRs). Thus, this study focused on 505 incident cases (79.8% of the initial cohort) from 13 centers. A total of 3681 rituximab infusions were administered, and 16.8% of the patients experienced at least one ADR. These were observed most frequently during the first infusion (44 patients, 52%) and the second infusion (17 patients, 20%). The most frequent reactions were general disorders and administration site conditions (n. 50, 8% serious). These findings support the clinical safety of rituximab biosimilars and suggest that switching between biosimilars does not increase the risk of adverse events. This evidence may alleviate concerns about biosimilar use, potentially leading to broader acceptance and reduced healthcare costs.
Published: 2024
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45. Identification of an immune-related genes signature in lung adenocarcinoma to predict survival and response to immune checkpoint inhibitors.

Author: Davoodi-Moghaddam Z, Jafari-Raddani F, Kordasti S, and Bashash D
Subjects: Humans, Prognosis, Male, Female, Biomarkers, Tumor genetics, Middle Aged, Lymphocytes, Tumor-Infiltrating immunology, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Aged, Transcriptome, Mutation, Computational Biology methods, Immune Checkpoint Inhibitors therapeutic use, Adenocarcinoma of Lung genetics, Adenocarcinoma of Lung drug therapy, Adenocarcinoma of Lung mortality, Adenocarcinoma of Lung immunology, Adenocarcinoma of Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms mortality, Lung Neoplasms immunology, Lung Neoplasms pathology
Abstract: Background: Although advances in immune checkpoint inhibitor (ICI) research have provided a new treatment approach for lung adenocarcinoma (LUAD) patients, their survival is still unsatisfactory, and there are issues in the era of response prediction to immunotherapy., Methods: Using bioinformatics methods, a prognostic signature was constructed, and its predictive ability was validated both in the internal and external datasets (GSE68465). We also explored the tumor-infiltrating immune cells, mutation profiles, and immunophenoscore (IPS) in the low-and high-risk groups., Results: As far as we are aware, this is the first study which introduces a novel prognostic signature model using BIRC5, CBLC, S100P, SHC3, ANOS1, VIPR1, LGR4, PGC, and IGKV4.1. According to multivariate analysis, the 9-immune-related genes (IRGs) signature provided an independent prognostic factor for the overall survival (OS). The low-risk group had better OS, and the tumor mutation burden (TMB) was significantly lower in this group. Moreover, the risk scores were negatively associated with the tumor-infiltrating immune cells, like CD8 + T cells, macrophages, dendritic cells, and NK cells. In addition, the IPS were significantly higher in the low-risk group as they had higher gene expression of immune checkpoints, suggesting that ICIs could be a promising treatment option for low-risk LUAD patients., Conclusion: The combination of these 9-IRGs not only could efficiently predict overall survival of LUAD patients but also show a powerful association with the expression of immune checkpoints and response to ICIs based on IPS; hoping this model paves the way for better stratification and management of patients in clinical practice., (© 2024. The Author(s).)
Published: 2024
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46. Dynamics of minimal residual disease and its clinical implications in multiple myeloma: A retrospective real-life analysis.

Author: Xu W, Liang X, Liu S, Yi X, Tian M, Yue T, Zhang Y, Yan Y, Lan M, Long M, Zhang N, Wang J, Sun X, Hu R, Zhu Y, Ma X, Cheng Y, Xu J, Dai Y, and Jin F
Abstract: Background: Minimal residual disease (MRD) testing is a promising approach to tailor the treatment of multiple myeloma (MM). However, several major concerns remain to be addressed before moving it into daily practice, most of which stem from the dynamic nature of the MRD status. Thus, it is crucial to understand the MRD dynamics and propose its clinical implications., Methods: We retrospectively analysed the data of patients with newly diagnosed MM (NDMM) who had flow cytometry-based MRD tests at multiple time points after initiation of therapy. The impact of undetectable MRD (including attainment, duration and loss) on clinical outcomes was analysed., Results: In a cohort of 220 patients with NDMM, attainment of MRD - offered favourable outcomes (P < 0.0001 for both progression-free survival (PFS) and overall survival (OS)), regardless of baseline risk factors. Notably, MRD - duration ≥12 months was associated with an 83 % (95 % confidence interval (CI), 0.09-0.34; P < 0.0001) or 69 % (95 % CI, 0.13-0.76; P = 0.0098) reduction in risk of progression/death or death, while the longer MRD - was sustained, the better the outcome was. Loss of MRD - led to poor PFS (hazard ratio (HR) 0.01, 95 % CI 0-0.06, P < 0.0001) and OS (HR 0.03, 95 % CI 0-0.24, P = 0.0008). Most patients (70 %) who lost MRD - status carried high-risk cytogenetic abnormalities (HRCAs). While MRD - was temporally inconsistent with conventional therapeutic responses (eg ≥ complete remission or very good partial response), it predicted disease progression or recurrence more robustly than the latter. Last, the predictive value of the MRD status was independent of baseline risk factors (eg high-risk cytogenetic abnormality, International Staging System (ISS) or Revised (R-)ISS staging)., Conclusions: Longitudinal assessment of MRD during the treatment course and follow-up is required for monitoring disease progression or relapse, to guide treatment decisions. Accordingly, a prospective study is currently ongoing to investigate the feasibility and benefit of the MRD-tailored therapy according to the longitudinal changes of the MRD status., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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47. IVLBCL mimicking VEXAS syndrome.

Author: Shopsowitz K, Abdulla A, and Moshref Razavi H
Subjects: Humans, Diagnosis, Differential, Lymphoma, B-Cell diagnosis
Abstract: Competing Interests: Declaration of interests We declare no competing interests.
Published: 2024
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48. What is best practice for the prevention of anti-D alloimmunisation in D-negative recipients receiving solid organ transplants from D-positive donors.

Author: Lynes T, Ying Li AM, Sexton D, Nasralla D, and Hazell M
Published: 2024
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49. Measurement of heparin, direct oral anti-coagulants and other non-coumarin anti-coagulants and their effects on haemostasis assays: A British Society for Haematology Guideline.

Author: Baker P, Platton S, Arachchillage DJ, Kitchen S, Patel J, Riat R, and Gomez K
Published: 2024
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50. Late effects after allogeneic haematopoietic cell transplantation in children and adolescents with non-malignant disorders: a retrospective cohort study.

Author: Kahn J, Brazauskas R, Bo-Subait S, Buchbinder D, Hamilton BK, Schoemans H, Abraham AA, Agrawal V, Auletta JJ, Badawy SM, Beitinjaneh A, Bhatt NS, Broglie L, Diaz Perez MA, Farhadfar N, Freytes CO, Gale RP, Ganguly S, Hayashi RJ, Hematti P, Hildebrandt GC, Inamoto Y, Kamble RT, Koo J, Lazarus HM, Mayo SJ, Mehta PA, Myers KC, Nishihori T, Prestidge T, Rotz SJ, Savani BN, Schears RM, Sharma A, Stenger E, Ustun C, Williams KM, Vrooman LM, Satwani P, and Phelan R
Subjects: Humans, Child, Retrospective Studies, Adolescent, Female, Male, Child, Preschool, Risk Factors, Incidence, Infant, Young Adult, Transplantation, Homologous adverse effects, Hematopoietic Stem Cell Transplantation adverse effects
Abstract: Background: Continued advances in haematopoietic cell transplantation (HCT) for children with non-malignant diseases (NMDs) have led to a growing population of survivors in whom late occurring toxic effects remain a challenge. We investigated the incidence of and risk factors for post-transplant toxicities in a contemporary cohort of children and adolescents undergoing HCT for NMDs., Methods: In this retrospective cohort study, we extracted data from the Center for International Blood and Marrow Transplantation Research (CIBMTR) database to analyse timing and incidence of effects and risk factors associated with late effects of HCT for treatment of NMDs at age 21 years or younger. Late effects of interest were avascular necrosis, cataracts, congestive heart failure, myocardial infarction, diabetes, gonadal dysfunction, growth hormone deficiency, hypothyroidism, renal failure requiring dialysis, and neurological events (stroke and seizure). Cumulative incidence of each late effect was calculated at 5 years and 7 years after HCT. Risk factors were evaluated in Cox proportional hazards regression analyses. Main exposures were primary NMD, age, sex, ethnicity and race, insurance, donor and graft type, myoablative conditioning, total-body irradiation exposure, graft-versus-host disease (GVHD), and transplant year. Primary outcomes were rates, cumulative incidence probability (95% CI), and risk-factors for organ-specific late effects., Findings: Between Jan 1, 2000, and Dec 31, 2017, 7785 patients aged 21 years or younger underwent HCT. 1995 patients were ineligible or did not consent to be included. 5790 patients from 171 centres were included in the analysis. 3505 (60·5%) of 5790 patients were male and 2285 (39·5%) were female. 2106 (36·4%) patients were White, 771 (13·3%) were Hispanic, and 773 (12·7%) were Black. 1790 (30·9%) patients were non-USA residents. Median age at HCT was 5·5 years (range 0·0-21·0). 1127 (19%) of 5790 patients had one late effect, and 381 (7%) had at least two. At 7 years post-HCT, the cumulative incidence probability was 1·9 (95% CI 1·5-2·3) for cataracts, 4·9 (4·3-5·6) for diabetes, 2·6 (2·1-3·1) for gonadal dysfunction, 3·2 (2·7-3·8) for hypothyroidism, 5·0 (4·4-5·7) for growth disturbance, 8·1 (7·4-8·9) for renal failure, 1·6 (1·3-2·0) for avascular necrosis, 0·6 (0·4-0·8) for congestive heart failure, 0·2 (0·1-0·3) for myocardial infarction, and 9·4 (8·6-10·2) for neurological effects. Age 10 years or older at HCT, unrelated donor source, total-body irradiation, and GVHD were identified as risk factors for long-term effects., Interpretation: The findings highlight the need for, and access to, multidisciplinary and lifelong follow-up for children undergoing HCT for NMDs. As more children undergo treatment with cellular therapies for non-malignant conditions, further analyses of post-transplant data could increasingly guide treatment decisions and subsequent long-term surveillance., Funding: National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration, and Office of Naval Research., Competing Interests: Declaration of interests BKH reports compensation from Nkarta ad hoc advisory board; serving on the Data Safety Monitoring Committee for Angiocrine; speaker fees from Therakos/Mallinkrodt; ad hoc advisory board participation for Kadmon/Sanofi and Equilium; and consulting for Incyte. HS reports compensation (personal fees paid to institution) from Incyte, Janssen, Novartis, Sanofi, and the Belgian Hematological Society; research grants (paid to institution) from Novartis and the BHS; non-financial support from Gilead, Pfizer, European Society for Blood and Marrow transplantation (EBMT) and Center for International Bone Marrow Transplantation Research (CIBMTR); and serving as a volunteer for EBMT, CIBMTR, and The European Patients' Academy on Therapeutic Innovation. JJA reports advisory board participation for AscellaHealth and Takeda. AB reports consulting fees from Kite. NF reports advisory board participation and consulting for Incyte. RPG reports consulting for Antengene Biotech LLC, Ascentage Pharma Group, and NexImmune; serving as the Medical Director for FFF Enterprises; serving on the Board of Directors for Russian Foundation for Cancer Research Support; and Scientific Advisory Board participation for Nanexa and StemRad. SG reports Advisory Board participation for AstraZeneca, Sanofi, Bristol Myers Squibb, and KITE Pharma. GCH reports consultancy or advisory boards for Seattle Genetics, Daiichy, Jannsen, Ono, Astra Zeneca, Sobi, and RapaTherapeutics; stocks with Axim, Cellectis, CVS Health, Cardinal Health, Pfizer, Bluebird Bio, Charlotte's web, Medical PTTYS TR, Moderna, Viatris, Biogen, Merck, Micron Technology, Mustang Bio, Neogenomics, Opko Health, Zevra Therapeutics, Clovis Oncology, AImmune, Caretrust Reit, Angi, and GW Pharmaceuticals; and research funding from Astra Zeneca and Incyte. PAM reports serving on the Board of Directors for Orthogon Therapeutics. KCM reports research funding (clinical trial) from Incyte and the National Institutes for Health (NIH) and industry sponsored (clinical trial) from Elixirgen Therapeutics. TN reports research support (to the institution) for clinical trial from Novartis; research support (drug supply only) to the institution for clinical trial from Karyopharm; and advisory board participation for Medexus. SJR reports being a paid medical monitor for the RCI and BMT. AS reports compensation (consulting) for Spotlight Therapeutics, Medexus, Vertex Pharmaceuticals, Sangamo Therapeutics, and Editas Medicine; serving as a medical monitor for RCI BMT CSIDE clinical trial which receives financial compensation; research funding from CRISPR Therapeutics; honoraria from Vindico Medical Education; serving as the St Jude Children's Research Hospital site principal investigator of clinical trials for genome editing of sickle cell disease sponsored by Vertex Pharmaceuticals and CRISPR Therapeutics (NCT03745287), Novartis Pharmaceuticals (NCT04443907) and Beam Therapeutics (NCT05456880). The industry sponsors provide funding for the clinical trial, which includes salary support paid to Dr Sharma's institution. Dr Sharma has no direct financial interest in these therapies. CU reports honoraria (speakers' bureau) from Bluprint and Takeda. KMW reports grant review and research funding from the National Heart, Lung, and Blood Institute, Leukemia Lymphoma Society, Rising Tide, and NIH; philanthropy funds from the Hudgens society and Legacy Peach Bowl; and travel compensation from American Society for Transplantation and Cellular Therapy, American Society of Hematology, and Pediatric Transplantation & Cellular Therapy Consortium. RP reports compensation (advisory board) from Bluebird Bio; and research funding from Amgen. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Published: 2024
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