29 results on '"Lise Willems"'
Number of results to display per page
Search Results
2. Accelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation
- Author
-
David Rombaut, Carine Lefèvre, Tony Rached, Sabrina Bondu, Anne Letessier, Raphael M. Mangione, Batoul Farhat, Auriane Lesieur-Pasquier, Daisy Castillo-Guzman, Ismael Boussaid, Chloé Friedrich, Aurore Tourville, Magali De Carvalho, Françoise Levavasseur, Marjorie Leduc, Morgane Le Gall, Sarah Battault, Marie Temple, Alexandre Houy, Didier Bouscary, Lise Willems, Sophie Park, Sophie Raynaud, Thomas Cluzeau, Emmanuelle Clappier, Pierre Fenaux, Lionel Adès, Raphael Margueron, Michel Wassef, Samar Alsafadi, Nicolas Chapuis, Olivier Kosmider, Eric Solary, Angelos Constantinou, Marc-Henri Stern, Nathalie Droin, Benoit Palancade, Benoit Miotto, Frédéric Chédin, and Michaela Fontenay
- Subjects
Science - Abstract
Abstract Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS. Compared to erythroblasts from SRSF2- or U2AF1-mutated patients, SF3B1-mutated erythroblasts exhibit augmented DNA synthesis, accelerated replication forks, and single-stranded DNA exposure upon differentiation. Importantly, histone deacetylase inhibition using vorinostat restores R-loop formation, slows down DNA replication forks and improves SF3B1-mutated erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress represents a hallmark of SF3B1-mutated MDS ineffective erythropoiesis, which could be used as a therapeutic target.
- Published
- 2024
- Full Text
- View/download PDF
3. VEXAS syndrome is characterized by inflammasome activation and monocyte dysregulation
- Author
-
Olivier Kosmider, Céline Possémé, Marie Templé, Aurélien Corneau, Francesco Carbone, Eugénie Duroyon, Paul Breillat, Twinu-Wilson Chirayath, Bénédicte Oules, Pierre Sohier, Marine Luka, Camille Gobeaux, Estibaliz Lazaro, Roderau Outh, Guillaume Le Guenno, François Lifermann, Marie Berleur, Melchior Le Mene, Chloé Friedrich, Cédric Lenormand, Thierry Weitten, Vivien Guillotin, Barbara Burroni, Jeremy Boussier, Lise Willems, Selim Aractingi, Léa Dionet, Pierre-Louis Tharaux, Béatrice Vergier, Pierre Raynaud, Hang-Korng Ea, Mickael Ménager, Darragh Duffy, and Benjamin Terrier
- Subjects
Science - Abstract
Abstract Acquired mutations in the UBA1 gene were recently identified in patients with severe adult-onset auto-inflammatory syndrome called VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). However, the precise physiological and clinical impact of these mutations remains poorly defined. Here we study a unique prospective cohort of VEXAS patients. We show that monocytes from VEXAS are quantitatively and qualitatively impaired and display features of exhaustion with aberrant expression of chemokine receptors. In peripheral blood from VEXAS patients, we identify an increase in circulating levels of many proinflammatory cytokines, including IL-1β and IL-18 which reflect inflammasome activation and markers of myeloid cells dysregulation. Gene expression analysis of whole blood confirms these findings and also reveals a significant enrichment of TNF-α and NFκB signaling pathways that can mediate cell death and inflammation. This study suggests that the control of the nflammasome activation and inflammatory cell death could be therapeutic targets in VEXAS syndrome.
- Published
- 2024
- Full Text
- View/download PDF
4. S162: LOSS OF HEMATOPOIETIC PROGENITORS HETEROGENEITY IS AN ADVERSE PROGNOSTIC FACTOR IN MYELODYSPLASTIC SYNDROMES
- Author
-
Charles Dussiau, Thibault Comont, Camille Knosp, Ines Vergnolle, Clotilde Bravetti, Alban Canali, Amandine Houvert, Laetitia Largeaud, Christian Daveaux, Laila Zaroili, Chloe Friedrich, Ismael Boussaid, Loria Zalmai, Carole Almire, Odile Beyne-Rauzy, Lise Willems, Didier Bouscary, Olivier Gandrillon, Michaela Fontenay, Oliver Kosmider, Francois Vergez, and Nicolas Chapuis
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
- Full Text
- View/download PDF
5. S232: EFFICACY AND TOXICITY OF CAR-T CELLS IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMAS, A NEW REFERENCE: THE FRENCH EXPERIENCE OF THE NATIONAL LOC NETWORK
- Author
-
Sylvain Choquet, Carole Soussain, Magali Legarff-Tavernier, Roberta DI Blasi, Laetitia Souchet, Damien Roos-Weil, Veronique Morel Malek, Madalina Uzunov, Carole Metz, Stéphanie Nguyen-Quoc, Nicolas Gauthier, Lise Willems, Agathe Waultier Rascalou, Celia Salanoubat, Roch Houot, Renata Ursu, Lionel Galicier, Maryline Barrie, Guido Ahle, Blandine Guffroy, Marion Alcantara, Khe Hoang-Xuan, and Caroline Houillier
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
- Full Text
- View/download PDF
6. Hematopoietic differentiation is characterized by a transient peak of entropy at a single-cell level
- Author
-
Charles Dussiau, Agathe Boussaroque, Mathilde Gaillard, Clotilde Bravetti, Laila Zaroili, Camille Knosp, Chloé Friedrich, Philippe Asquier, Lise Willems, Laurent Quint, Didier Bouscary, Michaela Fontenay, Thibault Espinasse, Adriana Plesa, Pierre Sujobert, Olivier Gandrillon, and Olivier Kosmider
- Subjects
Hematopoiesis ,Single-cell RNA-seq ,Cell-to-cell variability ,Entropy ,Myelodysplastic syndromes ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Mature blood cells arise from hematopoietic stem cells in the bone marrow by a process of differentiation along one of several different lineage trajectories. This is often represented as a series of discrete steps of increasing progenitor cell commitment to a given lineage, but as for differentiation in general, whether the process is instructive or stochastic remains controversial. Here, we examine this question by analyzing single-cell transcriptomic data from human bone marrow cells, assessing cell-to-cell variability along the trajectories of hematopoietic differentiation into four different types of mature blood cells. The instructive model predicts that cells will be following the same sequence of instructions and that there will be minimal variability of gene expression between them throughout the process, while the stochastic model predicts a role for cell-to-cell variability when lineage commitments are being made. Results Applying Shannon entropy to measure cell-to-cell variability among human hematopoietic bone marrow cells at the same stage of differentiation, we observed a transient peak of gene expression variability occurring at characteristic points in all hematopoietic differentiation pathways. Strikingly, the genes whose cell-to-cell variation of expression fluctuated the most over the course of a given differentiation trajectory are pathway-specific genes, whereas genes which showed the greatest variation of mean expression are common to all pathways. Finally, we showed that the level of cell-to-cell variation is increased in the most immature compartment of hematopoiesis in myelodysplastic syndromes. Conclusions These data suggest that human hematopoietic differentiation could be better conceptualized as a dynamical stochastic process with a transient stage of cellular indetermination, and strongly support the stochastic view of differentiation. They also highlight the need to consider the role of stochastic gene expression in complex physiological processes and pathologies such as cancers, paving the way for possible noise-based therapies through epigenetic regulation.
- Published
- 2022
- Full Text
- View/download PDF
7. Antimicrobial stewardship in high-risk febrile neutropenia patients
- Author
-
Adrien Contejean, Salam Abbara, Ryme Chentouh, Sophie Alviset, Eric Grignano, Nabil Gastli, Anne Casetta, Lise Willems, Etienne Canouï, Caroline Charlier, Frédéric Pène, Julien Charpentier, Jeanne Reboul-Marty, Rui Batista, Didier Bouscary, and Solen Kernéis
- Subjects
Antimicrobial stewardship ,High-risk febrile neutropenia ,Prognosis ,Antibiotic consumption ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background The 2011 4th European Conference on Infections in Leukemia (ECIL4) guidelines recommend antibiotics de-escalation/discontinuation in selected febrile neutropenia (FN) patients. We aimed to assess the impact of an antimicrobial stewardship (AMS) program based on these guidelines on antibiotics use and clinical outcomes in high-risk FN patients. Methods We conducted an observational study in the hematology department of Cochin University Hospital in Paris, France. An ECIL4-based antibiotics de-escalation and discontinuation strategy was implemented jointly by the hematologists and the AMS team. The pre-intervention (January–October 2018) and post-intervention (January-October 2019) periods were compared. We retrospectively collected clinical and microbiological data. We compiled antibiotics consumptions via hospital pharmacy data and standardized them by calculating defined daily doses per 1000 patient-days. We analyzed the two-monthly antibiotic consumption using an interrupted time series method and built a composite endpoint for clinical outcomes based on transfer to the intensive care unit (ICU) and/or hospital death. Results Overall, 273 hospital stays (164 patients) in the pre-intervention and 217 (148 patients) in the post-intervention periods were analyzed. Patients were mainly hospitalized for intensive chemotherapy for acute leukemia or autologous stem-cell transplant for myeloma. Patients were slightly younger in the pre-intervention compared to the post-intervention period (median age 60.4 vs 65.2 years, p = 0.049), but otherwise comparable. After implementation of the AMS program, glycopeptide and carbapenem use decreased by 85% (p = 0.03) and 72% (p = 0.04), respectively. After adjustment on confounders, the risk of transfer to the ICU/death decreased significantly after implementation of the AMS program (post-intervention period: odds-ratio = 0.29, 95% Confidence Interval: 0.15–0.53, p
- Published
- 2022
- Full Text
- View/download PDF
8. Subcutaneous azacitidine maintenance in transplantineligible patients with acute myeloid leukemia: a single-center retrospective study
- Author
-
Natacha Johnson, Marie Templé, Chloe Friedrich, Lise Willems, Rudy Birsen, Marguerite Vignon, Paul Deschamps, Patricia Franchi, Johanna Mondesir, Benedicte Deau-Fischer, Elsa Miekoutima, Ismaël Boussaid, Nicolas Chapuis, Olivier Kosmider, Didier Bouscary, Jerome Tamburini, and Justine Decroocq
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
- Full Text
- View/download PDF
9. Therapy-related Myeloid Neoplasms in Patients With Chronic Lymphocytic Leukemia Who Received FCR/FC as Frontline Therapy
- Author
-
Kamel Laribi, Alix Baugier de Materre, David Ghez, Caroline Dartigeas, Cécile Tomowiak, Béatrice Mahé, Jean-Baptiste Micol, Fatiha Merabet, Stéphane Leprêtre, Charles Herbaux, Loïc Ysebaert, Ronan Le Calloch, Lise Willems, Maud Voldoire, Damien Roos-Weil, Clotilde Bravetti, Yamina Touileb, Frédéric Davi, Florence Nguyen-Khac, Karim Maloum, and Marie C. Béné
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
- Full Text
- View/download PDF
10. Patients with Hematological Malignancies Treated with T-Cell or B-Cell Immunotherapy Remain at High Risk of Severe Forms of COVID-19 in the Omicron Era
- Author
-
Jeremie Zerbit, Marion Detroit, Antoine Meyer, Justine Decroocq, Benedicte Deau-Fischer, Paul Deschamps, Rudy Birsen, Johanna Mondesir, Patricia Franchi, Elsa Miekoutima, Corinne Guerin, Rui Batista, Didier Bouscary, Lise Willems, and Marguerite Vignon
- Subjects
COVID-19 ,hematology ,immunotherapy ,Microbiology ,QR1-502 - Abstract
Background: Patients with hematological malignancies are at greater risk of severe COVID-19 and have been prioritized for COVID-19 vaccination. A significant proportion of them have an impaired vaccine response, both due to the underlying disease and to the treatments. Methods: We conducted a prospective observational study to identify the specific risks of the outpatient population with hematological diseases. Result: Between 22 December 2021 to 12 February 2022, we followed 338 patients of which 16.9% (n = 57) developed SARS-CoV-2 infection despite previous vaccination (94.7%). COVID-19 patients were more likely to have received immunotherapy (85.5% vs. 41%, p < 10−4), and particularly anti-CD20 monoclonal antibodies (40% vs. 14.9%, p < 10−4) and Bruton’s tyrosine kinase inhibitors (BTKi) (7.3% vs. 0.7%, p < 10−2). There was no significant difference in demographic characteristics or hematological malignancies between COVID-19-positive and non-positive patients. Patients hospitalized for COVID-19 had more frequently received immunotherapy than patients with asymptomatic or benign forms (100% vs. 77.3%, p < 0.05). Hospitalized COVID-19 patients had a higher proportion of negative or weakly positive serologies than non-hospitalized patients (92.3% vs. 61%, p < 0.05). Patients who received tixagevimab/cilgavimab prophylaxis (n = 102) were less likely to be COVID-19-positive (4.9 vs. 22%, p < 0.05) without significant difference in hospitalization rates. Conclusion: In the immunocompromised population of patients with hematological malignancies, the underlying treatment of blood cancer by immunotherapy appears to be a risk factor for SARS-CoV-2 infection and for developing a severe form.
- Published
- 2022
- Full Text
- View/download PDF
11. Characteristics and Outcomes of Adult Patients with T Prolymphocytic Leukemia: A Real World Study of the French Innovative Leukemia Group (FILO)
- Author
-
Kamel Laribi, Loic Ysebaert, Luca Inchiappa, Bruno Villemagne, Yann Guillermin, Jérôme Paillassa, Fatiha Merabet, Cécile Guénot, Alix Baugier de Materre, Charles Herbaux, Kristell Mahe, Marion Divoux, Caroline Algrin, Stephane Lepretre, Damien Roos Weil, Cécile Tomowiak, David Ghez, Stéphanie Poulain, Marion Loirat, Caroline Dartigeas, Lise Willems, Olivier Tournilhac, and Marie C Bene
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
- Full Text
- View/download PDF
12. CAR T-cell therapy in primary central nervous system lymphoma: the clinical experience of the French LOC network
- Author
-
Marion Alcantara, Caroline Houillier, Marie Blonski, Marie-Thérèse Rubio, Lise Willems, Agathe Waultier Rascalou, Magali Le Garff-Tavernier, Karim Maloum, Clotilde Bravetti, Laetitia Souchet, Damien Roos-Weil, Véronique Morel, Madalina Uzunov, Carole Metz, Meriem Dhib-Charfi, Stéphanie Nguyen, Natalia Shor, Dimitri Psimaras, Nicolas Weiss, Nathalie Jacque, Silvia Solorzano, Nicolas Gauthier, Marie Le Cann, Françoise Norol, Carole Soussain, and Sylvain Choquet
- Subjects
Central Nervous System ,Male ,Immunology ,Cell Biology ,Hematology ,Middle Aged ,Immunotherapy, Adoptive ,Survival Analysis ,Biochemistry ,Central Nervous System Neoplasms ,Cohort Studies ,Humans ,Female ,France ,Lymphoma, Large B-Cell, Diffuse ,Letter to Blood ,Aged - Published
- 2022
- Full Text
- View/download PDF
13. Supplementary Figures 1 - 4 from Dual Inhibition of PI3K and mTORC1/2 Signaling by NVP-BEZ235 as a New Therapeutic Strategy for Acute Myeloid Leukemia
- Author
-
Didier Bouscary, Patrick Mayeux, Catherine Lacombe, Olivier Herault, François Dreyfus, Norbert Ifrah, Sauveur-Michel Maira, Alexandre Macone, Sophie Park, Lise Willems, Melanie Pannetier, Aymeric Neyret, Valerie Bardet, Christine Vignon, Alexa S. Green, Jerome Tamburini, and Nicolas Chapuis
- Abstract
PDF file - 202K
- Published
- 2023
- Full Text
- View/download PDF
14. Data from Dual Inhibition of PI3K and mTORC1/2 Signaling by NVP-BEZ235 as a New Therapeutic Strategy for Acute Myeloid Leukemia
- Author
-
Didier Bouscary, Patrick Mayeux, Catherine Lacombe, Olivier Herault, François Dreyfus, Norbert Ifrah, Sauveur-Michel Maira, Alexandre Macone, Sophie Park, Lise Willems, Melanie Pannetier, Aymeric Neyret, Valerie Bardet, Christine Vignon, Alexa S. Green, Jerome Tamburini, and Nicolas Chapuis
- Abstract
Purpose: The growth and survival of acute myeloid leukemia (AML) cells are enhanced by the deregulation of signaling pathways such as phosphoinositide 3-kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR). Major efforts have thus been made to develop molecules targeting these activated pathways. The mTOR serine/threonine kinase belongs to two separate complexes: mTORC1 and mTORC2. The mTORC1 pathway is rapamycin sensitive and controls protein translation through the phosphorylation of 4E-BP1 in most models. In AML, however, the translation process is deregulated and rapamycin resistant. Furthermore, the activity of PI3K/Akt and mTOR is closely related, as mTORC2 activates the oncogenic kinase Akt. We therefore tested, in this study, the antileukemic activity of the dual PI3K/mTOR ATP-competitive inhibitor NVP-BEZ235 compound (Novartis).Experimental Design: The activity of NVP-BEZ235 was tested in primary AML samples (n = 21) and human leukemic cell lines. The different signaling pathways were analyzed by Western blotting. The cap-dependent mRNA translation was studied by 7-methyl-GTP pull-down experiments, polysomal analysis, and [3H]leucine incorporation assays. The antileukemic activity of NVP-BEZ235 was tested by analyzing its effects on leukemic progenitor clonogenicity, blast cell proliferation, and survival.Results: The NVP-BEZ235 compound was found to inhibit PI3K and mTORC1 signaling and also mTORC2 activity. Furthermore, NVP-BEZ235 fully inhibits the rapamycin-resistant phosphorylation of 4E-BP1, resulting in a marked inhibition of protein translation in AML cells. Hence, NVP-BEZ235 reduces the proliferation rate and induces an important apoptotic response in AML cells without affecting normal CD34+ survival.Conclusions: Our results clearly show the antileukemic efficiency of the NVP-BEZ235 compound, which therefore represents a promising option for future AML therapies. Clin Cancer Res; 16(22); 5424–35. ©2010 AACR.
- Published
- 2023
- Full Text
- View/download PDF
15. Supplementary Figure Legend, Table 1 from Dual Inhibition of PI3K and mTORC1/2 Signaling by NVP-BEZ235 as a New Therapeutic Strategy for Acute Myeloid Leukemia
- Author
-
Didier Bouscary, Patrick Mayeux, Catherine Lacombe, Olivier Herault, François Dreyfus, Norbert Ifrah, Sauveur-Michel Maira, Alexandre Macone, Sophie Park, Lise Willems, Melanie Pannetier, Aymeric Neyret, Valerie Bardet, Christine Vignon, Alexa S. Green, Jerome Tamburini, and Nicolas Chapuis
- Abstract
PDF file - 109K
- Published
- 2023
- Full Text
- View/download PDF
16. Haemolytic paroxysmal nocturnal haemoglobinuria in patients with myeloid neoplasms: A rare association with specific therapeutic implications
- Author
-
Aurélien Sutra del Galy, Lise Willems, Maud D'Aveni, Cécile Pautas, Sylvain Chantepie, Benjamin Carpentier, Fiorenza Barraco, Anne Banos, Reda Garidi, Edouard Forcade, Flore Sicre de Fontbrune, and Régis Peffault de Latour
- Subjects
Hematology - Published
- 2023
- Full Text
- View/download PDF
17. Pharmaceutical cancer care for haematology patients on oral anticancer drugs: Findings from an economic, clinical and organisational analysis
- Author
-
Jeremie Zerbit, Marie Kroemer, Basile Fuchs, Marion Detroit, Justine Decroocq, Marguerite Vignon, Lise Willems, Bénédicte Deau‐Fischer, Patricia Franchi, Paul Deschamps, Adrien Contejean, Eric Grignano, Guillemette Fouquet, Rudy Birsen, Johanna Mondesir, Mathieu Rocquet, Jean‐François Huon, Rui Batista, Jeanne Marty‐Reboul, and Didier Bouscary
- Subjects
Pharmaceutical Preparations ,Oncology ,Neoplasms ,Cost-Benefit Analysis ,Humans ,Antineoplastic Agents ,Prospective Studies ,Hematology ,Pharmacists ,Pharmacy Service, Hospital - Abstract
The clinical benefit of pharmaceutical cares in improving the quality-of-care outcomes is well demonstrated. Clinical pharmacy services are not systematically deployed in cancer units in the absence of economic data. The aim of this prospective, observational 1-year study was to evaluate the clinical, economic and organisational impacts of pharmaceutical care into a multidisciplinary day hospital for patients treated with oral cancer drugs.All pharmacists' interventions (PI) were documented and their impact and the probability of adverse drug events were assessed using the clinical, economic and organisational tool.Among 360 admissions, an average of 1.81 PI per admission was accepted. Among 452 PI leading to a clinical benefit on the patient, 16.9% had a major impact, and 1.9% had an impact on survival. The large majority of PIs (87%) increased the quality-of-care organisation. The budget impact model showed a total cost savings and cost avoidance of €539,047 per year and a cost-benefit ratio of 7.07:1. The direct cost-benefit was €201,741, and the cost avoidance was €337,306.Multidisciplinary care and pharmaceutical care are key elements to improve cancer patients' outcomes and avoid evitable healthcare costs.
- Published
- 2022
- Full Text
- View/download PDF
18. Immune thrombocytopenia and pregnancy: an exposed/nonexposed cohort study
- Author
-
Stéphanie Guillet, Valentine Loustau, Emmanuelle Boutin, Anissa Zarour, Thibault Comont, Odile Souchaud-Debouverie, Nathalie Costedoat Chalumeau, Brigitte Pan-Petesch, Delphine Gobert, Stéphane Cheze, Jean Francois Viallard, Anne-Sophie Morin, Gaetan Sauvetre, Manuel Cliquennois, Bruno Royer, Agathe Masseau, Louis Terriou, Claire Fieschi, Olivier Lambotte, Stéphane Girault, Bertrand Lioger, Sylvain Audia, Karim Sacre, Jean Christophe Lega, Vincent Langlois, Alexandra Benachi, Corentin Orvain, Alain Devidas, Sebastien Humbert, Nicolas Gambier, Marc Ruivard, Virginie Zarrouk, Mikael Ebbo, Lise Willems, Lauriane Segaux, Matthieu Mahevas, Bassam Haddad, Marc Michel, Florence Canoui-Poitrine, Bertrand Godeau, Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Etablissement Français du Sang [Île-de-France Mondor], IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de référence maladie rare des cytopénies auto-immunes de l'adulte (GECAI - Hôpital Henri-Mondor - UPEC), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Service de Génomique Fonctionnelle, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), 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), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Brest (UBO), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Université de Bordeaux (UB), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hopital Saint-Louis [AP-HP] (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Médecine Interne - Immunologie Clinique [AP-HP Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Hématologie biologique [CHU Limoges], and CHU Limoges
- Subjects
Purpura, Thrombocytopenic, Idiopathic ,Immunology ,Pregnancy Complications, Hematologic ,Infant, Newborn ,Cell Biology ,Hematology ,Biochemistry ,Cohort Studies ,Thrombocytopenia, Neonatal Alloimmune ,Pregnancy ,Humans ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Female ,Prospective Studies ,Retrospective Studies - Abstract
The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (
- Published
- 2022
- Full Text
- View/download PDF
19. Management of Gastro-Intestinal Toxicity of the Pi3 Kinase Inhibitor: Optimizing Future Dosing Strategies
- Author
-
Claire Breal, Frederic Beuvon, Thibault de Witasse-Thezy, Solene Dermine, Patricia Franchi-Rezgui, Benedicte Deau-Fisher, Lise Willems, Eric Grignano, Adrien Contejean, Didier Bouscary, Jean Luc Faillie, Jean-Marc Treluyer, Corinne Guerin, Laurent Chouchana, and Marguerite Vignon
- Subjects
Cancer Research ,Oncology - Abstract
The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in cancer progression and in host immunity. Idelalisib was the first of this class to be approved with the second-generation Pi3 kinase inhibitors copanlisib, duvelisib and umbralisib, subsequently being approved in the United States. Real-world data are lacking, however, in relation to the incidence and toxicity of Pi3 kinase inhibitor-induced colitis. We here review, in the first instance, the general landscape of the Pi3K inhibitors in the context of hematological malignancies, with a focus on the adverse gastrointestinal side effects reported by various clinical trials. We further review the available worldwide pharmacovigilance data in relation to these drugs. Finally, we describe our own real-world experience with idelalisib-induced colitis management in our center and in a national setting.
- Published
- 2023
- Full Text
- View/download PDF
20. Long-Term Follow-up of Bendamustine Plus Rituximab Regimen in 69 Treatment Naïve (TN) Patients with Waldenström Macroglobulinemia, a Study on Behalf of the French Innovative Leukemia Organization (FILO)
- Author
-
Kamel Laribi, Stéphanie Poulain, Lise Willems, Fatiha Merabet, Charles Herbaux, Damien Roos Weil, Alix Baugier de Materre, Xavier Roussel, Sabine Tricot, Jehan Dupuis, Ronan Le Calloch, Benoit Bareau, Marie C Béné, and Veronique Leblond
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
- Full Text
- View/download PDF
21. DNA Replication Stress Due to Loss of R-Loops in Myelodysplastic Syndromes with SF3B1 Mutation
- Author
-
David Rombaut, Carine Lefevre, Batoul Farhat, Sabrina Bondu, Anne Letessier, Auriane Lesieur-Pasquier, Daisy Castillo-Guzman, Marjorie Leduc, Emilie-Fleur Gautier, Virginie Chesnais, Alice Rousseau, Ismael Boussaid, Sarah Battault, Alexandre Houy, Didier Bouscary, Lise Willems, Nicolas Chapuis, Sophie Park, Sophie Raynaud, Thomas Cluzeau, Emmanuelle Clappier, Pierre Fenaux, Lionel Ades, Eric Solary, Raphael Margueron, Michel Wassef, Olivier Kosmider, Samar Alsafadi, Nathalie Droin, Angelos Constantinou, Marc-Henri Stern, Benoit Miotto, Frederic Chedin, and Michaela Fontenay
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
- Full Text
- View/download PDF
22. Thrombosis with Non-Proliferative Complete Blood Count Indicative of Underlying Myeloproliferative Neoplasm, Sythrom, a Study on Behalf of the FIM Group
- Author
-
Yannick LE Bris, Jean Galtier, Dina Naguib, Mathieu Wemeau, Jean Claude Chomel, Laurence Legros, Yan Beauverd, Lise Willems, Guillaume Denis, Françoise Boyer perrard, Damien Luque-Paz, Kamel Laribi, Mélanie Mercier, Pascale Cony-Makhoul, Olivier Herault, Lydia Roy, Pierre Sujobert, Lenaig Le Clech, Sylvie Tondeur, Gaelle Laboure, Jerome Rey, Guillou Sophie, Cedric Pastoret, Pascaline Etancelin, Suzanne Tavitian, Charles Bescond, Francois Girodon, Shanti Amé, Viviane Dubruille, Eric Lippert, Chloe James, Barbara Burroni, Marc Fouassier, Marie C Béné, and Jean Christophe Ianotto
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
- Full Text
- View/download PDF
23. Reduced peripheral blood dendritic cell and monocyte subsets in MDS patients with systemic inflammatory or dysimmune diseases
- Author
-
Vincent, Jachiet, Laure, Ricard, Pierre, Hirsch, Florent, Malard, Laurent, Pascal, Odile, Beyne-Rauzy, Pierre, Peterlin, Alexandre Thibault Jacques, Maria, Norbert, Vey, Maud, D'Aveni, Marie-Pierre, Gourin, Sophie, Dimicoli-Salazar, Anne, Banos, Stefan, Wickenhauser, Louis, Terriou, Benoit, De Renzis, Eric, Durot, Shanti, Natarajan-Ame, Anne, Vekhoff, Laurent, Voillat, Sophie, Park, Julien, Vinit, Céline, Dieval, Azeddine, Dellal, Vincent, Grobost, Lise, Willems, Julien, Rossignol, Eric, Solary, Olivier, Kosmider, Nicolas, Dulphy, Lin Pierre, Zhao, Lionel, Adès, Pierre, Fenaux, Olivier, Fain, Mohamad, Mohty, Béatrice, Gaugler, and Arsène, Mekinian
- Abstract
Systemic inflammatory and autoimmune diseases (SIADs) occur in 10-20% of patients with myelodysplastic syndrome (MDS). Recently identified VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, associated with somatic mutations in UBA1 (Ubiquitin-like modifier-activating enzyme 1), encompasses a range of severe inflammatory conditions along with hematological abnormalities, including MDS. The pathophysiological mechanisms underlying the association between MDS and SIADs remain largely unknown, especially the roles of different myeloid immune cell subsets. The aim of this study was to quantitatively evaluate peripheral blood myeloid immune cells (dendritic cells (DC) and monocytes) by flow cytometry in MDS patients with associated SIAD (n = 14, most often including relapsing polychondritis or neutrophilic dermatoses) and to compare their distribution in MDS patients without SIAD (n = 23) and healthy controls (n = 7). Most MDS and MDS/SIAD patients had low-risk MDS. Eight of 14 (57%) MDS/SIAD patients carried UBA1 somatic mutations, defining VEXAS syndrome.Compared with MDS patients, most DC and monocyte subsets were significantly decreased in MDS/SIAD patients, especially in MDS patients with VEXAS syndrome. Our study provides the first overview of the peripheral blood immune myeloid cell distribution in MDS patients with associated SIADs and raises several hypotheses: possible redistribution to inflammation sites, increased apoptosis, or impaired development in the bone marrow.
- Published
- 2022
24. Anti-CD38 therapy impairs SARS-CoV-2 vaccine response against alpha and delta variants in patients with multiple myeloma
- Author
-
Soledad Henriquez, Jérémie Zerbit, Timothée Bruel, Amani Ouedrani, Delphine Planas, Paul Deschamps, Isabelle Staropoli, Jérôme Hadjadj, Bruno Varet, Natalia Ermak, Didier Bouscary, Lise Willems, Guillemette Fouquet, Justine Decroocq, Patricia Franchi, Benedicte Deau-Fischer, Benjamin Terrier, Jérôme Tamburini, Lucienne Chatenoud, Olivier Schwartz, Marguerite Vignon, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Necker - Enfants Malades [AP-HP], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université de Genève (UNIGE), Université Paris Descartes - Paris 5 (UPD5), This study was supported by Fonds IMMUNOV for Innovation in Immunopathology, by the Institut Pasteur (for work in the OS laboratory), the Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale, and ANRS, and by grants from the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, and IDISCOVR. D.P. is supported by the Vaccine Research Institute., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Université de Genève = University of Geneva (UNIGE)
- Subjects
Immunology ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Cell Biology ,Hematology ,Biochemistry ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2022
- Full Text
- View/download PDF
25. VEXAS Syndrome Is Characterized by Blood and Tissues Inflammasome Pathway Activation and Monocyte Dysregulation
- Author
-
Olivier Kosmider, Céline Possémé, Marie Templé, Aurélien Corneau, Francesco Carbone, Eugénie Duroyon, Twinu-Wilson Chirayath, Marine Luka, Camille Gobeaux, Estibaliz Lazaro, Roderau Outh, Guillaume Le Guenno, François Lifermann, Marie Berleur, Chloé Friedrich, Cédric Lenormand, Thierry Weitten, Vivien Guillotin, Barbara Burroni, Pierre Sohier, Jay Boussier, Lise Willems, Selim Aractingi, Léa Dionet, Pierre-Louis Tharaux, Béatrice Vergier, Pierre Raynaud, Hang-Korng Ea, Mickael Ménager, Darragh Duffy, and Benjamin Terrier
- Subjects
History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Abstract
SUMMARYAcquired mutations in theUBA1gene, occurring in myeloid cells and resulting in expression of a catalytically impaired isoform of the enzyme E1, were recently identified in patients with severe adult-onset auto-inflammatory syndrome called VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic). The precise physiological and clinical impact of these mutations remains poorly defined.Here, we studied a unique prospective cohort of individuals with severe autoinflammatory disease with (VEXAS) or without (VEXAS-like)UBA1somatic mutations and compared with low-risk myelodysplastic syndromes (MDS) and aged gender-matched healthy controls. We performed an integrated immune analysis including multiparameter phenotyping of peripheral blood leukocytes, cytokines profiling, bulk and single-cell gene expression analyses and skin tissue imaging mass cytometry.Focusing on myeloid cells, we show that monocytes fromUBA1-mutated individuals were quantitatively and qualitatively impaired and displayed features of exhaustion with aberrant expression of chemokine receptors. Within affected tissues, pathological skin biopsies from VEXAS patients showed an abundant enrichment of CD16+CD163+monocytes adjacent to blood vessels and M1 macrophages, possibly promoting local inflammation in part through STAT3 activation. In peripheral blood from VEXAS patients, we identified a significant increase in circulating levels of many proinflammatory cytokines, including IL-1β and IL-18 which reflect inflammasome activation and markers of myeloid cells dysregulation. Gene expression analysis of whole blood confirmed the role of circulating cells in the IL-1β and IL-18 dysregulation in VEXAS patients and revealed a significant enrichment of TNF-α and NFκB signaling pathways that could mediate cell death and inflammation. Single-cell analysis confirmed the inflammatory state of monocytes from VEXAS patients and allowed us to identify specific molecular pathways that could explain monocytopenia, especially the activation of PANoptosis and a deficiency in the TYROBP/DAP12 axis and β-catenin signaling pathway. Together, these findings on monocytes from patients withUBA1mutations provide important insights into the molecular mechanisms involving the mature myeloid commitment in VEXAS syndrome and suggest that the control of the undescribed inflammasome activation and PANoptosis could be novel therapeutic targets in this condition.GRAPHICAL ABSTRACT
- Published
- 2022
- Full Text
- View/download PDF
26. Therapy-related Myeloid Neoplasms in Patients With Chronic Lymphocytic Leukemia Who Received FCR/FC as Frontline Therapy
- Author
-
Kamel Laribi, Alix Baugier de Materre, David Ghez, Caroline Dartigeas, Cécile Tomowiak, Béatrice Mahé, Jean-Baptiste Micol, Fatiha Merabet, Stéphane Leprêtre, Charles Herbaux, Loïc Ysebaert, Ronan Le Calloch, Lise Willems, Maud Voldoire, Damien Roos-Weil, Clotilde Bravetti, Yamina Touileb, Frédéric Davi, Florence Nguyen-Khac, Karim Maloum, and Marie C. Béné
- Subjects
Hematology - Published
- 2021
27. Humoral response to mRNA anti–COVID-19 vaccines BNT162b2 and mRNA-1273 inpatients with chronic lymphocytic leukemia
- Author
-
Stéphanie Malartre, Cristina Bagacean, Véronique Leblond, Aline Clavert, Hugo Legendre, Caroline Dartigeas, Nanthara Sritharan, Bernard Drenou, Kamel Laribi, Xavier Troussard, Ségolène Brichler, Anne-Sophie Michallet, Driss Chaoui, Alain Delmer, Lise Willems, Christian Puppinck, Cécile Tomowiak, Fatiha Merabet, Damien Roos-Weil, Chadi Al-Nawakil, Florence Cymbalista, Rémi Letestu, Marie C. Béné, Romain Guieze, Vincent Levy, Philippe Genet, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne (UCA)
- Subjects
medicine.medical_specialty ,COVID-19 Vaccines ,medicine.drug_class ,Chronic lymphocytic leukemia ,Monoclonal antibody ,Antibodies, Viral ,Gastroenterology ,chemistry.chemical_compound ,Chemoimmunotherapy ,Internal medicine ,medicine ,Humans ,RNA, Messenger ,Seroconversion ,BNT162 Vaccine ,Aged ,Response rate (survey) ,Messenger RNA ,Venetoclax ,business.industry ,SARS-CoV-2 ,COVID-19 ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Hematology ,medicine.disease ,Stimulus Report ,Leukemia, Lymphocytic, Chronic, B-Cell ,Vaccination ,mRNA vaccine ,chemistry ,third dose ,business ,CLL ,2019-nCoV Vaccine mRNA-1273 - Abstract
Immunocompromised individuals such as patients with chronic lymphocytic leukemia (CLL) are at risk of impaired immune responses to vaccination. The objective of our study was to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific antibody responses in patients with CLL after the first, second, and third doses of the BNT162b2 or mRNA-1273 vaccines and after a single dose for patients with confirmed previous COVID-19. In all, 530 patients were included in the study. Patients received 2 doses at a 4-week interval and a third dose if they were seronegative after the second dose. Response rate was 27% after dose 1 and 52% after dose 2. Post-dose 2 treatment-naïve patients had the highest response rate (72%) followed by patients previously treated by chemoimmunotherapy (60%). Among patients receiving therapy, those receiving Bruton tyrosine kinase inhibitor alone (22%) or in combination with anti-CD20 monoclonal antibodies or venetoclax (0%) had the poorer response rate whereas patients who received venetoclax monotherapy achieved a significantly higher response rate (52%). A multivariable analysis identified age older than 65 years, ongoing CLL treatment, and gamma globulin ≤6 g/L as independent predictors of the absence of seroconversion. Post-dose 2 seronegative patients had a global response rate of 35% after dose 3. This study provides an argument for the use of a third dose and for prophylactic SARS-CoV-2 neutralizing monoclonal antibodies.
- Published
- 2021
- Full Text
- View/download PDF
28. Humoral Response to mRNA Vaccines BNT162b2 and mRNA-1273 COVID-19 in Chronic Lymphocytic Leukemia Patients
- Author
-
Damien Roos-Weil, Alain Delmer, Lise Willems, Xavier Troussard, Nanthara Sritharan, Aline Clavert, Anne-Sophie Michallet, Philippe Genet, Hugo Legendre, Cristina Bagacean, Véronique Leblond, Caroline Dartigeas, Kamel Laribi, Bernard Drenou, Fatiha Merabet, Christian Puppink, Vincent Levy, Yamina Touileb, Cécile Tomowiak, Stéphanie Malartre, Rémi Letestu, Driss Chaoui, Florence Cymbalista, Chadi Al Nawakil, Romain Guieze, Marie C. Béné, and Ségolène Brichler
- Subjects
Messenger RNA ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Chronic lymphocytic leukemia ,Immunology ,642.Chronic Lymphocytic Leukemia: Clinical and Epidemiological ,Medicine ,Cell Biology ,Hematology ,business ,medicine.disease ,Biochemistry - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an ongoing global pandemic. Phase III trials have demonstrated excellent efficacies of mRNA vaccines against SARS-CoV-2 in large population studies (Baden LR, NEJM, 2021; Polack FP, NEJM, 2020). Immunosuppressed individuals such as chronic lymphocytic leukemia (CLL) patients are at risk for a suboptimal response to 2 vaccine doses (Herishanu Y, Blood, 2021). The French National Authority for Health recommends the use of a third dose in immunosuppressed patients. However, seroconversion rate after the triple-dose vaccine is not yet known. The objective of our study was to evaluate SARS-CoV-2 antibody responses after the first, second and third doses of the BNT162b2 and mRNA-1273 vaccines. Data were collected from 17 French Innovative Leukemia Organization (FILO) investigating centers and the French CLL patients' association (SILLC). SARS-CoV-2 IgG anti-Spike levels were measured at 4-6 weeks after each vaccine dose. A total of 530 patients and 14 controls were included in the study. Vaccine response was evaluated post-dose 1 for 158 CLL patients, post-dose 2, for 506 patients and post-dose 3 for 66 patients. Peripheral blood lymphocyte subsets were studied post-dose 2 by flow cytometry in 80 CLL patients and 14 controls. The median age of the patients was 71 years (range 37-93), 218 (40%) were treatment-naïve (TN), 136 (26%) had a prior CLL treatment and 176 (34%) were on therapy. Post-dose 1, the global response rate was 27% (43/158). TN patients had a response rate of 34% (23/67), similar to those who had a prior CLL treatment (33%,12/36), and higher compared to on-therapy patients (15%, 8/55, P=0.02). Post-dose 2, the global response rate was 52% (265/506). TN patients had the highest response rate of 72% (151/210) compared to previously treated patients, mostly by immunochemotherapy (60%, 78/130, P=0.02) and on-therapy patients (22%, 36/166, P65 years (OR 0.55, 95% CI 0.33-0.92, P=0.02), ongoing CLL treatment (OR 0.13, 95% CI 0.07-0.23, P Flow cytometry results suggest a differential balance of the T CD4+ cell subpopulations in Binet stage A and in patients on targeted therapy compared to healthy controls. Post-dose 2 seronegative patients were proposed a third dose and to date, 66 have been tested for the antibody response 4-6 weeks post-dose 3. The post-dose 3 response rate was 42% (28/66). TN patients and previously treated patients had a significantly higher response rate (57%, 16/28) compared to on-therapy patients (32%, 12/38, P=0.03). We further analyzed patients tested post-dose 2 with the Abbott Architect SARS-CoV-2 IgG anti-Spike assay (n=24). Those who achieved seroconversion after the third dose (n=10) had significantly higher titers post-dose 2 (median 12, IQR 3.0-40.8) compared to those who remained seronegative (n=14) (median 2.2, IQR 0.5-5.1, p An additional cohort of 40 CLL patients who presented a SARS-CoV-2 infection prior to vaccination participated to the study and was analyzed independently. All patients achieved seroconversion after infection and a single dose of vaccine, even though 30% (n=12) had an ongoing CLL treatment. In conclusion, double-dose mRNA vaccination generated a humoral response in 52% of our CLL cohort and a third dose induced seroconversion in 42% of the patients who remained seronegative after the second dose. The major independent predictor of negative antibody response was ongoing treatment with BTKi. The strongest boost to immune response against the virus seems to be SARS-CoV-2 infection, as a substantial increase in anti-Spike antibodies was observed in all CLL patients with prior infection, after a single dose vaccination. Figure 1 Figure 1. Disclosures Letestu: Janssen: Research Funding, Speakers Bureau; Roche: Speakers Bureau; AbbVie: Research Funding, Speakers Bureau. Dartigeas: Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress. Laribi: Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; AstraZeneca: Other: Personal Fees; IQONE: Other: Personal Fees; AbbVie: Other: Personal Fees, Research Funding; Takeda: Other: Personal Fees, Research Funding; Novartis: Other: Personal Fees, Research Funding; Le Mans Hospital: Research Funding; Jansen: Research Funding. Cymbalista: Lilly-LOXO: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; ASTRA ZENECA: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees.
- Published
- 2021
29. Auteurs
- Author
-
Laetitia, Amalou, Cédric, Annweiler, Élise, Artaud-Macari, Alexis, Arvin-Bérod, Patrick, Assayag, Maria, Bailleul, Emma, Bajeux, Grégory, Baptista, Martine, Barateau, Bernard, Bauduceau, Laetitia, Beernaert, Joël, Belmin, Athanase, Bénétos, Michel, Benoit, Hubert, Blain, Sylva, Blazkova, Wanda, Blervaque, Sylvie, Bonin-Guillaume, Mylène, Bonnaire, Marc, Bonnefoy, Mathilde, Bordage, Lyse, Bordier, Chokri, Boubakri, Didier, Bouccara, Anne-Sophie, Boureau, Bruneau, Marie-Andrée, Pierre-Emmanuel, Cailleaux, Priscille, Carvalho, Philippe, Chassagne, Aline, Corvol, Matthieu, Coulongeat, Antoine, Cuvelier, Sandra, De Breucker, Laure, De Decker, Tristan, De Nattes, Amandine, Dessertennes, Audrey, De Vos, Benoît, de Wazières, Frédéric, Di Fiore, Aurélien, Dinh, Cristiano, Donadio, Jean-Michel, Dorey, Jean, Doucet, Olivier, Drunat, Feriel, Fennira, Claire, Falandry, Juliette, Fontaine, Thibaut, Fraisse, Patrick, Friocourt, Tamàs, Fülöp, Julien, Gaudric, Jean-Bernard, Gauvain, Gaëtan, Gavazzi, Xavier, Gbaguidi, Charles-Emmanuel, Geffroy, Christian, Geny, Édouard, Georgeton, Baptiste, Gérard, Angélique, Giacomini, Mathilde, Gisselbrecht, Alice, Gochard-Rodrigues, Bernard, Goichot, Régis, Gonthier, Odile, Goria, Adrien, Grancher, Béatrice, Guérin, Dominique, Guerrot, Olivier, Hanon, Charlotte, Havreng-Théry, Réjean, Hébert, Mathieu, Herrmann, Patrick, Hidoux, Jérémie, Huet, Witold, Jarzebowski, Olivier, Jeanjean, Georges, Kaltenbach, Alain, Koskas, Pierre, Krolak-Salmon, Carmelo, Lafuente-Lafuente, Pierre-Olivier, Lang, Martine, Le Noc Soudani, Amandine, Lecarpentier, Laurent, Lechowski, Pierre-Olivier, Lefebvre, Anne, Léger, Caroline, Lemaitre, Thierry, Lequerré, Anaïs, Lesourd, Pierre, Lutzler, Arach, Madjlessi, Éric, Maeker, Emmanuel, Maheu, Patrick, Manckoundia, Nathalie, Maubourguet, Sylvie, Meaume, Anne, Michel, Boubacar, Mohamed, Hélène, Montialoux, Sophie, Moulias, France, Mourey, Stéphane, Nacache, Sylvain, N'Guyen, Charlotte, Nouhaud, Jean-Luc, Novella, Christel, Oasi, Marine, Olivieri, Bruno, Oquendo, Mourad, Ould Slimane, Marc, Paccalin, Elena, Paillaud, Frédéric, Pamoukdjian, Sylvie, Pariel, Erika, Parmentier-Decrucq, Christine, Perret-Guillaume, Mélissa-Asli, Petit, François, Pinoche, Julien, Poissy, Valérie, Pouysségur, Isabelle, Prêcheur, Alain, Putot, Yasmine, Rassam-Hasso, Agathe, Raynaud-Simon, Clothilde, Riquier, Frédéric, Roca, Jean, Roche, Pierre-Alexandre, Roger, Nathalie, Salles, Patricia, Senet, Dominique, Somme, Carmen, Suna-Enache, Alain, Tavildari, Achille, Tchalla, Laurent, Teillet, Lise, Teisseire, Cathy, Théry, Éric, Vérin, Maurice, Viala, Marguerite, Vignon, Olivier, Vittecoq, Eugenia, Volpentesta, Lise, Willems, Alberto, Zalar, Sabrina, Aït, Gilles, Albrand, Jean-Pierre, Aquino, André, Aurengo, Odile, Baugé-Faraldi, Nadine, Bazin, Jean-Louis, Beaudeux, Xavier, Belenfant, Lotfi, Ben Slama, Athanase, Benetos, Jean-Marc, Bereder, Gilles, Berrut, François, Blanchard, Jacques, Boddaert, Christophe, Bouché, Rabia, Boulahssass, Isabelle, Bourdel-Marchasson, Anne, Bruhat, Marie-Andrée, Bruneau, Agnès, Camus, Corinne, Capet, Emmanuelle, Champion, Dominique, Chavanne, Patrick, Chérin, Florence, Chopin, Thierry, Constans, Pascal, Couturier, Véronique, Cressot, Laure, de Decker, Anne-Sophie, De Saint-Léger, Benoit, De Wazières, Philippe, Denormandie, Violaine, Derambure, Laurent, Druesne, Bernard, Durand-Gasselin, Richard, Durant, Marc, Faraldi, Anne-Laure, Fauchais, Audrey, Fel, Éric, François, Florent, François, Éric, Frau, Jacques, Gaillat, Danièle, Ganem-Chabenet, David, Gaucher, Pierre, Gauthier, Gaël, Gendron, Armelle, Gentric, Laura, Goodrich, Isabelle, Got, Etty, Grynberg, Jean-Michel, Guérin, Olivier, Guerin, Karine, Guignery-Kadri, Bernard, Guillot, Victor, Haddad, Pierre, Haond, Cyril, Hazif-Thomas, Jacqueline, Henry, François, Héron, Géraldine, Heurteux, Caroline<ce:sup loc='post">†</ce:sup>, Hommet, Marc, Humbert, Cécile, Hvostoff, Jean-Marc, Jacquot, Claude, Jeandel, Nadir, Kadri, Norelyakin, Kara, Aïda, Kerkeni, Aïni, Khris, Kiyoka, Kinugawa, Rémy, Klein, Emmanuel, Krupka, Marc, Labétoulle, Gilles, Lascault, Julien, Le Guen, Cédric, Le Guillou, Véronique, Lefebvre des Noëttes, Daniel, Letonturier, Caroline, Levasseur, Jean-Pierre, Louvel, Emmanuelle, Magny, Nicolas-Dominique, Manchon, Dominique, Manière, Jean, Mariani, Sophie, Marilier, Thierry, Marquet, Charlotte, Mathon, Emmanuel, Mazen, Anthony, Mézière, Pierre, Michel Jean, Christelle, Mischis-Troussard, Anne-Sophie, Moiziard, A., Morais José, Robert, Moulias, Andy, Musat, Angela, Musat, Cathy, Nabet, Henry, Noguès, Fati, Nourhashémi, Fannie, Onen, Hakki, Onen S., Yves, Otmezguine, Béatrice, Pallot-Prades, Marie-Pierre, Pancrazi, Maxime, Patout, Éric, Pautas, Jérôme, Pellerin, Renaud, Péquignot, Benoît, Pernot, Anne, Petit, Pierre<ce:sup loc='post">†</ce:sup>, Pfitzenmeyer, Benoît, Plaud, Emilie, Puget, François, Puisieux, Lucie, Quibel, Muriel, Rainfray, Cyrielle, Rambaud, Vincent, Rialle, Yves, Rolland, Jean-Nicolas, Royal, Guillaume, Savard, Jean-Pierre, Schuster, Denise, Strubel, Catherine, Terrat, Catherine, Terret, Jean-Étienne, Terrier, Daniel, Tessier, Sarah, Thomas, Thierry, Thomas, Christophe, Trivalle, Lucie, Valembois, Bruno, Vellas, Éric, Verin, Marc, Verny, Marie, Vetel Jean, Pierre, Veyssier, Thomas, Vogel, and Fabienne, Wirotius
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Books, media, physical & digital resources
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.