134 results on '"Nicolas Blin"'
Search Results
2. P927: ACTUAL USAGE OF CURRENT SYSTEMIC TREATMENTS AND INFLUENCE OF KEY DRIVERS FOR MULTIPLE MYELOMA IN THE FIRST 2 LINES OF THERAPY. DATA FROM REAL-WORLD STUDY IN EU5 COUNTRIES.
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Nicolas Blin, Siegfried Ertl, Elodie Schneider, and Christine Mai
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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3. Safety and immunogenicity of a first dose of SARS‐CoV‐2 mRNA vaccine in allogeneic hematopoietic stem‐cells recipients
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Patrice Chevallier, Marianne Coste‐Burel, Amandine Le Bourgeois, Pierre Peterlin, Alice Garnier, Marie C. Béné, Berthe‐Marie Imbert, Thomas Drumel, Steven Le Gouill, Philippe Moreau, Beatrice Mahe, Viviane Dubruille, Nicolas Blin, Anne Lok, Cyrille Touzeau, Thomas Gastinne, Maxime Jullien, Sophie Vanthygem, and Thierry Guillaume
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract This was a monocentric prospective study testing the efficacy and safety of a first injection of BNT162b2 (Pfizer‐BioNTech) in 112 Allo‐HSCT patients. Antibody response to SARS‐CoV‐2 spike protein receptor‐binding domain was tested at the time of the second injection (Roche Elecsys). The study also included a non‐randomized control arm of 26 healthy controls. This study shows that a first dose of SARS‐CoV‐2 messenger RNA vaccine is safe and provides a 55% rate of seroconversion in allotransplanted patients compared to 100% for the controls (p
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- 2021
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4. A new cytokine‐based dynamic stratification during induction is highly predictive of survivals in acute myeloid leukemia
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Pierre Peterlin, Joelle Gaschet, Thierry Guillaume, Alice Garnier, Marion Eveillard, Amandine Le Bourgeois, Michel Cherel, Camille Debord, Yannick Le Bris, Olivier Theisen, Catherine Godon, Béatrice Mahé, Viviane Dubruille, Soraya Wuilleme, Cyrille Touzeau, Thomas Gastinne, Nicolas Blin, Anne Lok, Benoît Tessoulin, Steven Le Gouill, Philippe Moreau, Marie‐C Béné, and Patrice Chevallier
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acute myeloid leukemia ,FLT3 ligand ,IL‐6 ,prognostic biomarker ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract The aim of this study was to assess the potential impact of the kinetics of serum levels of seven cytokines during induction in acute myeloid leukemia (AML) patients. Indeed, the role of cytokines, in the pathophysiology and response to therapy of AML patients, remains under investigation. Here, we report on the impact of peripheral levels of two cytokines, the Fms‐like tyrosine kinase 3 ligand (FL) and interleukin‐6 (IL‐6), evaluated during first‐line intensive induction. A new risk stratification can be proposed, which supersedes the ELN 2017 classification to predict survivals in AML patients by examining the kinetic profile of these cytokines during the induction phase. It segregates three groups of, respectively, high‐risk, characterized by a stagnation of low FL levels, intermediate risk, with dynamic increasing FL levels and high IL‐6 at day 22, and favorable risk with increasing FL levels but low IL‐6 at day 22.
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- 2021
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5. RAS mutation leading to acquired resistance to dabrafenib and trametinib therapy in a multiple myeloma patient harboring BRAF mutation
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Baptiste Le Calvez, Yannick Le Bris, Guillaume Herbreteau, Bastien Jamet, Céline Bossard, Benoit Tessoulin, Thomas Gastinne, Béatrice Mahé, Viviane Dubruille, Nicolas Blin, Chloé Antier, Olivier Theisen, Françoise Kraeber‐Bodéré, Steven Le Gouill, Marie C. Béné, Philippe Moreau, and Cyrille Touzeau
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BRAF ,dabrafenib ,multiple myeloma ,RAS ,trametinib ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Multiple myeloma (MM) is still considered incurable and new therapeutic approaches are therefore needed. Deep‐sequencing analysis revealed the presence of BRAF mutations in up to 15% of patients. The clinical experience of BRAF‐targeted therapy in myeloma patients harboring BRAF mutation is still limited. We here report the case of a patient with penta‐refractory (bortezomib, lenalidomide, carfilzomib, pomalidomide, and daratumumab) MM with extramedullary BRAF‐mutated disease that achieved clinical response to dual BRAF and MEK inhibition. At the time of disease progression, gene sequencing analysis of the tumor at the time of progression demonstrated a clonal evolution with emergence of a NRAS mutation and persistence of BRAF and TP53 mutations. Backtracking of the NRAS mutation was performed by digital polymerase chain reaction on the baseline biopsy and identified the pre‐existence of the NRAS at a subclonal level. This observation is the first report of acquired NRAS mutation leading to resistance to dual BRAF/MEK inhibitors in MM. These data suggest that a systematic search for RAS mutations using highly sensitive techniques should be performed before considering targeted therapy in relapsed myeloma with BRAF mutation.
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- 2020
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6. FLT3 ligand plasma levels in acute myeloid leukemia
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Pierre Peterlin, Joelle Gaschet, Thierry Guillaume, Alice Garnier, Marion Eveillard, Amandine Le Bourgeois, Michel Cherel, Camille Debord, Yannick Le Bris, Olivier Theisen, Béatrice Mahé, Viviane Dubruille, Catherine Godon, Nelly Robillard, Soraya Wuilleme, Cyrille Touzeau, Thomas Gastinne, Nicolas Blin, Anne Lok, Antoine Bonnet, Steven Le Gouill, Philippe Moreau, Marie-C Béné, and Patrice Chevallier
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2019
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7. Deep and sustained response after venetoclax therapy in a patient with very advanced refractory myeloma with translocation t(11;14)
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Cyrille Touzeau, Steven Le Gouill, Béatrice Mahé, Jean Samuel Boudreault, Thomas Gastinne, Nicolas Blin, Hélène Caillon, Christelle Dousset, Martine Amiot, and Philippe Moreau
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2017
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8. A comparison of harmonic modeling methods with application to control of switched systems with active filtering.
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Nicolas Blin, Pierre Riedinger, Jamal Daafouz, Louis Grimaud, and Philippe Feyel
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- 2019
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9. An unusual case of acute kidney injury in a patient with IgA paraproteinemia. Lessons for the clinical nephrologist
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Yannick Le Bris, Nicolas Blin, Charles Ronsin, Clément Deltombe, Simon Ville, and Christine Kandel-Aznar
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Nephrology ,medicine.medical_specialty ,Paraproteinemia ,Unusual case ,business.industry ,Paraproteinemias ,Acute kidney injury ,Waldenstrom macroglobulinemia ,Acute Kidney Injury ,medicine.disease ,Dermatology ,Immunoglobulin A ,Nephrologists ,Internal medicine ,Humans ,Medicine ,Waldenstrom Macroglobulinemia ,Multiple Myeloma ,business - Published
- 2021
10. La transition vers l’âge adulte: une période charnière dans la prise en charge continue des jeunes patients
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Nicolas Blin, Bénédicte Thomas, Aline Schmidt, Céline Vergne, Stéphanie Proust, Jérémie Mallet, and Marie-Pierre Moles
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0301 basic medicine ,Gerontology ,Cancer Research ,media_common.quotation_subject ,digestive, oral, and skin physiology ,Multitude ,Identity (social science) ,Hematology ,General Medicine ,Disease ,Social issues ,Acculturation ,Psychic ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Radiology, Nuclear Medicine and imaging ,Meaning (existential) ,Psychology ,Autonomy ,media_common - Abstract
In recent decades, follow-up of cancer survivors has taken on its full meaning with the gradual improvement in the survival of children and adolescents with cancer. This follow-up is associated specially for adolescents with a multitude of transitions: the transition from therapeutic management to the monitoring for possible relapse, the transition into long-term follow-up after childhood cancer, the transition from a pediatric system to an adult care system. If this transition can be perceived as difficult by patients, it gives young people the opportunity to access more autonomous follow-up and support in becoming an adult. Supporting the transition should make caregivers attentive to this time of consolidation of adolescence, favorable to the emergence of a sense of stable, mature identity that guarantees a certain autonomy. This is a key to a successful transition limiting breakdown of care and promoting "the work of the disease". The double contribution of adult and pediatric oncology provides support tailored to these psychic and societal issues. AYA teams can actively participate in this process by facilitating the acculturation of pediatric and adult care teams to the specificity of this group, thus allowing a continuum of care.
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- 2021
11. A new cytokine‐based dynamic stratification during induction is highly predictive of survivals in acute myeloid leukemia
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Amandine Le Bourgeois, Marion Eveillard, Camille Debord, Joëlle Gaschet, Marie-C. Béné, Cyrille Touzeau, Soraya Wuilleme, Michel Chérel, Thierry Guillaume, Thomas Gastinne, Patrice Chevallier, Philippe Moreau, Catherine Godon, Benoit Tessoulin, Beatrice Mahe, Olivier Theisen, Nicolas Blin, Alice Garnier, Viviane Dubruille, Anne Lok, Pierre Peterlin, Yannick Le Bris, Steven Le Gouill, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), CRLCC René Gauducheau, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,Response to therapy ,medicine.medical_treatment ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,prognostic biomarker ,Original Research ,Potential impact ,biology ,Myeloid leukemia ,Induction Chemotherapy ,Middle Aged ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Pathophysiology ,3. Good health ,Survival Rate ,Leukemia, Myeloid, Acute ,Cytokine ,030220 oncology & carcinogenesis ,Female ,Adult ,medicine.medical_specialty ,Induction Phase ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,acute myeloid leukemia ,lcsh:RC254-282 ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,medicine ,Biomarkers, Tumor ,Humans ,FLT3 ligand ,Radiology, Nuclear Medicine and imaging ,Interleukin 6 ,Aged ,IL-6 ,business.industry ,Interleukin-6 ,Clinical Cancer Research ,Membrane Proteins ,IL‐6 ,030104 developmental biology ,biology.protein ,business ,Intermediate risk ,Follow-Up Studies - Abstract
The aim of this study was to assess the potential impact of the kinetics of serum levels of seven cytokines during induction in acute myeloid leukemia (AML) patients. Indeed, the role of cytokines, in the pathophysiology and response to therapy of AML patients, remains under investigation. Here, we report on the impact of peripheral levels of two cytokines, the Fms‐like tyrosine kinase 3 ligand (FL) and interleukin‐6 (IL‐6), evaluated during first‐line intensive induction. A new risk stratification can be proposed, which supersedes the ELN 2017 classification to predict survivals in AML patients by examining the kinetic profile of these cytokines during the induction phase. It segregates three groups of, respectively, high‐risk, characterized by a stagnation of low FL levels, intermediate risk, with dynamic increasing FL levels and high IL‐6 at day 22, and favorable risk with increasing FL levels but low IL‐6 at day 22., Here we report on the impact of the peripheral levels of two cytokines, the Fms‐like tyrosine kinase 3 ligand (FL), and interleukin‐6 (IL‐6), evaluated during first‐line intensive induction. Indeed, a new risk stratification can be proposed, which supersedes the ELN 2017 classification to predict survivals in AML patients by examining their profile during the induction phase.
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- 2021
12. Post-CAR T-Cell Early Reconstitution of Peripheral T-Cell Subsets Is Heterogeneous and Independent of the Cell Therapy Outcome in High Grade B-Cell Lymphoma
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Baptiste Le Calvez, Yannick Le Bris, Thomas Gastinne, Viviane Dubruille, Béatrice Mahé, Nicolas Blin, Anne Lok, Sophie Vantyghem, Clara Sortais, Cyrille Touzeau, Steven Le Gouill, Philippe Moreau, Patrice Chevallier, Marion Eveillard, Marie C Bene, and Benoit Tessoulin
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
13. Biological Differences between Axi-Cel and Tisa-Cel Products and Impacts on Outcomes in Lymphoma Patients
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Benoit Tessoulin, Audrey Grain, Jocelyn Ollier, Thomas Gastinne, Viviane Dubruille, Béatrice Mahé, Nicolas Blin, Anne Lok, Sophie Vantyghem, Clara Sortais, Cyrille Touzeau, Philippe Moreau, Steven Le Gouill, Patrice Chevallier, and Beatrice Clemenceau
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
14. Hematopoietic stem cell transplantation for acute lymphoblastic leukemia: why do adolescents and young adults outcomes differ from those of children? A retrospective study on behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)
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Audrey Grain, Fanny Rialland, Patrice Chevallier, Nicolas Blin, Jean-Hugues Dalle, Gérard Michel, Nathalie Dhédin, Régis Peffault de Latour, Cécile Pochon, Ibrahim Yakoub-Agha, Yves Bertrand, Anne Sirvent, Charlotte Jubert, Edouard Forcade, Ana Berceanu, Virginie Gandemer, Pascale Schneider, Jacques-Olivier Bay, Pierre-Simon Rohrlich, Eolia Brissot, Catherine Paillard, Dominique Plantaz, Stéphanie Nguyen Quoc, Fanny Gonzales, Natacha Maillard, Lucie Planche, Andre Baruchel, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Robert Debré, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), 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), Hospices Civils de Lyon (HCL), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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)-Centre National de la Recherche Scientifique (CNRS), and None
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MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma ,MESH: Adolescent ,Cancer Research ,MESH: Humans ,MESH: Child, Preschool ,MESH: Graft vs Host Disease ,Hematopoietic stem cell transplantation ,MESH: Adult ,MESH: Retrospective Studies ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,General Medicine ,Acute lymphoblastic leukemia ,Graft versus host disease ,MESH: Infant ,humanities ,Adolescents and young adults ,Oncology ,MESH: Young Adult ,hemic and lymphatic diseases ,MESH: Child ,MESH: Hematopoietic Stem Cell Transplantation - Abstract
International audience; Purpose: In the acute lymphoblastic leukemia (ALL) landscape, adolescents and young adults (AYA) often present high-risk diseases and increased chemotherapy-related toxicity. Studies analyzing the outcomes of AYA after hematopoietic stem cell transplantation (HSCT) are scarce. Our study aimed to compare the outcomes of children and AYA with ALL after HSCT and to determine the factors influencing potential differences.Method: 891 patients, from the SFGM-TC registry, aged between 1 and 25 years who received HSCT between 2005 and 2012 were included. The outcomes of AYA were compared to the ones of their younger counterparts.Results: Five-year OS and GRFS were lower in AYA: 53.1% versus 64% and 36% versus 47% (p = 0.0012 and p = 0.007, respectively). WhileCIR was similar in both groups, 5 year-treatment related mortality was higher in AYA: 19% versus 13% (p = 0.04). The lower GRFS in AYA was mainly explained by a higher chronic graft versus host disease (cGvHD) incidence: 32% versus 19% (p < 0.001). Use of peripheral blood stem cells and use of anti-thymoglobulin appeared to be the main factors impacting cGvHD occurrence in AYA.Conclusion: AYA have worse outcomes than children after HSCT for ALL because of a greater risk of TRM due to cGvHD. HSCT practices should be questioned in this population.Keywords: Acute lymphoblastic leukemia; Adolescents and young adults; Graft versus host disease; Hematopoietic stem cell transplantation.
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- 2022
15. Grade 2 acute GVHD is a factor of good prognosis in patients receiving peripheral blood stem cells haplo-transplant with post-transplant cyclophosphamide
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Steven Le Gouill, Ana Berceanu, A. Dormoy, Patrice Chevallier, Yohan Desbrosses, Caroline Malugani, Céline Bressollette, Berthe-Marie Imbert, Benoit Tessoulin, Thomas Gastinne, Eric Deconinck, Beatrice Mahe, Nicolas Blin, Philippe Moreau, Thierry Guillaume, Marie C. Béné, Marion Eveillard, Sophie Vantyghem, Amandine Le Bourgeois, Alix Duquesne, Etienne Daguindau, Yannick Le Bris, Alice Garnier, Cyrille Touzeau, Viviane Dubruille, Anne Lok, and Pierre Peterlin
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Post transplant cyclophosphamide ,Graft vs Host Disease ,Peripheral Blood Stem Cells ,Gastroenterology ,030218 nuclear medicine & medical imaging ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,immune system diseases ,Internal medicine ,Acute graft versus host disease ,medicine ,Humans ,Clofarabine ,Radiology, Nuclear Medicine and imaging ,In patient ,Cyclophosphamide ,Aged ,Retrospective Studies ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,Peripheral blood ,surgical procedures, operative ,Oncology ,030220 oncology & carcinogenesis ,Female ,Good prognosis ,business ,medicine.drug - Abstract
The impact of acute graft versus host disease (GVHD) on survivals for patients receiving a haploidentical allogeneic stem-cell transplant (Allo-SCT) with peripheral blood stem-cells (PBSC) complemented by post-transplant cyclophosphamide (PTCY) is ill-known.This retrospective study included 131 patients who received a PBSC haplograft in order to precise the impact of acute GVHD on outcomes. There were 78 males and 53 females and the median age for the whole cohort was 59 years (range: 20-71). Thirty-five patients were allografted for a lymphoid disease and 96 for a myeloid malignancy, including 67 patients with acute myeloid leukemia (AML).The cumulative incidence (CI) of day 100 grade 2-4 and 3-4 acute GVHD was 43.4 + 4.6% and 16.7 + 3.4%, respectively. The 2-year CI of moderate/severe chronic GVHD was 10.1 + 2.8%. The only factor affecting the occurrence of GVHD was GVHD prophylaxis. Indeed, CI of day 100 grade 2-4 (but not grade 3-4) acute GVHD was significantly reduced when adding anti-thymoglobulin (ATG) to PTCY. However, in multivariate analysis, grade 2 acute GVHD was significantly associated with better disease-free (HR: 0.36; 95%CI: 0.19-0.69,Acute grade 2 GVHD is a factor of good prognosis after PBSC haplotransplant with PTCY. Further and larger studies are needed to clarify the complex question of GVHD prophylaxis in the setting of haplo-transplant, especially that of combining ATG and PTCY.
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- 2020
16. Absence of influence of peripheral blood CD34+ and CD3+ graft cell counts on outcomes after reduced-intensity conditioning transplantation using post-transplant cyclophosphamide
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Beatrice Mahe, Nicolas Blin, Alix Duquesne, Alice Garnier, Anne Lok, Pierre Peterlin, Marie C. Béné, Marion Eveillard, Amandine Le Bourgeois, Thomas Gastinne, Thierry Guillaume, Viviane Dubruille, Cyrille Touzeau, Philippe Moreau, Steven Le Gouill, Patrice Chevallier, and Benoit Tessoulin
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,CD3 Complex ,Cyclophosphamide ,Antigens, CD34 ,Context (language use) ,Gastroenterology ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Clofarabine ,Aged ,Retrospective Studies ,Hematology ,business.industry ,Incidence (epidemiology) ,Graft Survival ,Hematopoietic Stem Cell Transplantation ,General Medicine ,Middle Aged ,Fludarabine ,Transplantation ,Treatment Outcome ,030220 oncology & carcinogenesis ,Cohort ,Female ,business ,Immunosuppressive Agents ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
The influence of peripheral blood stem cell (PBSC) graft cell contents after transplant with post-transplant cyclophosphamide (PTCY) remains unclear. Here, we retrospectively report on a cohort of 77 adults who received a Baltimore-based reduced-intensity conditioning regimen either with fludarabine (n = 40) or clofarabine (n = 37) and PTCY. With a median follow-up of 29.2 months, [2-]year overall (OS), disease-free (DFS), and GVHD/relapse-free survival (GRFS) rates were 62.8%, 51%, and 36.7%, respectively. The incidence of grades [2–]4 acute GVHD was significantly higher in patients transplanted with a haplodonor (n = 56), at 57.1% vs 19% (p = 0.006). PBSC graft cell contents (CD45+, CD34+, and CD3+ cells) had no impact on any outcome. Considering immune reconstitution until 1 year, only monocytes were above the normal range (as early as day + 30) during the first year post-transplant. In multivariate analysis, an older donor (> 45 years) and a high/very high disease risk index were independently associated with lower OS. A higher monocyte count (> median) at day + 90 was also associated with better OS, DFS, and GRFS. Donor/recipient CMV status matching was independently associated with GRFS. In conclusion, our data support the fact that there is no need to manipulate the graft before infusion in the particular context of PBSC/PTCY Baltimore-based allotransplant.
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- 2020
17. Max-tree Computation on GPUs
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Nicolas Blin, Edwin Carlinet, Florian Lemaitre, Lionel Lacassagne, Thierry Geraud, and Carlinet, Edwin
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graph algorithms ,Computational Theory and Mathematics ,max-tree ,[INFO.INFO-TI] Computer Science [cs]/Image Processing [eess.IV] ,Hardware and Architecture ,Mathematical morphology ,Signal Processing ,[INFO.INFO-DC] Computer Science [cs]/Distributed, Parallel, and Cluster Computing [cs.DC] ,hierarchical image representation ,component-trees - Abstract
In Mathematical Morphology, the max-tree is a region-based representation that encodes the inclusion relationship of the threshold sets of an image. This tree has proved useful in numerous image processing applications. For the last decade, work has led to improving the construction time of this structure; mixing algorithmic optimizations, parallel and distributed computing. Nevertheless, there is still no algorithm that benefits from the computing power of the massively parallel architectures. In this work, we propose the first GPU algorithm to compute the max-tree. The proposed approach leads to significant speed-ups, and is up to one order of magnitude faster than the current State-of-the-Art parallel CPU algorithms. This work paves the way for a max-tree integration in image processing GPU pipelines and real-time image processing based on Mathematical Morphology. It is also a foundation for porting other image representations from Mathematical Morphology on GPUs.
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- 2022
18. B Cell Aplasia Is the Most Powerful Predictive Marker for Poor Humoral Response after BNT162b2 mRNA SARS-CoV-2 Vaccination in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
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Maxime Jullien, Amandine Le Bourgeois, Marianne Coste-Burel, Pierre Peterlin, Alice Garnier, Marie Rimbert, Berthe-Marie Imbert, Steven Le Gouill, Philippe Moreau, Beatrice Mahe, Viviane Dubruille, Nicolas Blin, Anne Lok, Cyrille Touzeau, Thomas Gastinne, Benoit Tessoulin, Sophie Vantyghem, Marie C. Béné, Thierry Guillaume, and Patrice Chevallier
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Transplantation ,COVID-19 Vaccines ,SARS-CoV-2 ,Vaccination ,Hematopoietic Stem Cell Transplantation ,COVID-19 ,Cell Biology ,Hematology ,CD8-Positive T-Lymphocytes ,Molecular Medicine ,Immunology and Allergy ,Humans ,RNA, Messenger ,BNT162 Vaccine ,Biomarkers - Abstract
Little is known about the immune response to SARS-CoV-2 vaccination in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, several studies have reported that adequate protection could be provided to this population. The purpose of this study was to evaluate which factors can predict the efficacy of SARS-CoV-2 vaccination in these specifically immunosuppressed patients. Specific anti-Spike (S) antibody responses were assessed in a cohort of 117 allo-HSCT recipients after 2 injections of BNT162b2 mRNA SARS-CoV-2 vaccine (V1 and V2). Factors considered liable to influence the antibody response and analyzed in this series were the interval between allo-HSCT and V1, donor source, recipient and donor age, current immunosuppressive/chemotherapy (I/C) treatment, and levels of CD4
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- 2021
19. The temporal origin of dentate granule neurons dictates their role in spatial memory
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Daniela Cota, Valérie Lemaire, Marie-Françoise Montaron, Fanny Farrugia, Shaoyu Ge, Sophie Tronel, Vanessa Charrier, Wilfrid Mazier, Giovanni Marsicano, Nicolas Blin, Cyril Herry, Nuria Masachs, Djoher Nora Abrous, Véronique Deroche-Gamonet, Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Program in Neuroscience, SUNY at Stony Brook, stony brook, Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Stony Brook University [SUNY] (SBU), State University of New York (SUNY), and tronel, sophie
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Neurons ,0303 health sciences ,Dentate gyrus ,Period (gene) ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Cognition ,Optogenetics ,Biology ,Memory processing ,Rats ,Functional imaging ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,0302 clinical medicine ,Dentate Gyrus ,Animals ,Premovement neuronal activity ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Molecular Biology ,Neuroscience ,030217 neurology & neurosurgery ,Spatial Memory ,030304 developmental biology - Abstract
The dentate gyrus is one of the only brain regions that continues its development after birth in rodents. Adolescence is a very sensitive period during which cognitive competences are programmed. We investigated the role of dentate granule neurons (DGNs) born during adolescence in spatial memory and compared them with those generated earlier in life (in embryos or neonates) or during adulthood by combining functional imaging, retroviral and optogenetic tools to tag and silence DGNs. By imaging DGNs expressing Zif268, a proxy for neuronal activity, we found that neurons generated in adolescent rats (and not embryos or neonates) are transiently involved in spatial memory processing. In contrast, adult-generated DGNs are recruited at a later time point when animals are older. A causal relationship between the temporal origin of DGNs and spatial memory was confirmed by silencing DGNs in behaving animals. Our results demonstrate that the emergence of spatial memory depends on neurons born during adolescence, a function later assumed by neurons generated during adulthood.
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- 2021
20. Safety and antibody response after one and/or two doses of BNT162b2 Anti‐SARS‐CoV‐2 mRNA vaccine in patients treated by CAR T cells therapy
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Anne Lok, Pierre Peterlin, Viviane Dubruille, Steven Le Gouill, Sophie Vanthygem, Marianne Coste-Burel, Patrice Chevallier, Benoit Tessoulin, Berthe-Marie Imbert, Marie C. Béné, Nicolas Blin, Philippe Moreau, Thomas Drumel, Alice Garnier, Thierry Guillaume, Amandine Le Bourgeois, Beatrice Mahe, Maxime Jullien, Thomas Gastinne, Cyrille Touzeau, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Bernardo, Elizabeth, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
- Subjects
Male ,Antibodies, Viral ,Immunotherapy, Adoptive ,Immunogenicity, Vaccine ,0302 clinical medicine ,vaccine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,CAR‐T cells ,030212 general & internal medicine ,Antigens, Viral ,ComputingMilieux_MISCELLANEOUS ,Receptors, Chimeric Antigen ,Lymphoma, Non-Hodgkin ,Vaccination ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,SARS-CoV-2 mRNA ,Combined Modality Therapy ,3. Good health ,030220 oncology & carcinogenesis ,Spike Glycoprotein, Coronavirus ,Female ,Car t cells ,COVID 19 ,Adult ,2019-20 coronavirus outbreak ,Fever ,Coronavirus disease 2019 (COVID-19) ,CAR-T cells ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunization, Secondary ,Receptors, Antigen, T-Cell ,Pain ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,SARS‐CoV‐2 mRNA ,Immunocompromised Host ,Young Adult ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Correspondence ,Humans ,In patient ,BNT162 Vaccine ,Aged ,Biological Products ,Messenger RNA ,SARS-CoV-2 ,business.industry ,COVID-19 ,Virology ,Antibody response ,Immunoglobulin G ,BNT162b2 ,business - Abstract
International audience; No abstract available
- Published
- 2021
21. Safety and immunogenicity of a first dose of SARS‐CoV‐2 mRNA vaccine in allogeneic hematopoietic stem‐cells recipients
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Marie C. Béné, Philippe Moreau, Thomas Drumel, Sophie Vanthygem, Thomas Gastinne, Maxime Jullien, Amandine Le Bourgeois, Thierry Guillaume, Viviane Dubruille, Berthe-Marie Imbert, Cyrille Touzeau, Steven Le Gouill, Alice Garnier, Marianne Coste-Burel, Anne Lok, Pierre Peterlin, Patrice Chevallier, Beatrice Mahe, and Nicolas Blin
- Subjects
Chemotherapy ,business.industry ,Immunogenicity ,medicine.medical_treatment ,Short Report ,Transplantation ,Vaccination ,Haematopoiesis ,Immunology ,Medicine ,Seroconversion ,Stem cell ,business ,Prospective cohort study - Abstract
This was a monocentric prospective study testing the efficacy and safety of a first injection of BNT162b2 (Pfizer‐BioNTech) in 112 Allo‐HSCT patients. Antibody response to SARS‐CoV‐2 spike protein receptor‐binding domain was tested at the time of the second injection (Roche Elecsys). The study also included a non‐randomized control arm of 26 healthy controls. This study shows that a first dose of SARS‐CoV‐2 messenger RNA vaccine is safe and provides a 55% rate of seroconversion in allotransplanted patients compared to 100% for the controls (p
- Published
- 2021
22. Single-agent daratumumab in very advanced relapsed and refractory multiple myeloma patients: a real-life single-center retrospective study
- Author
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Philippe Moreau, Thierry Guillaume, Antoine Bonnet, Anne Lok, Pierre Peterlin, Viviane Dubruille, Patrick Thomaré, Benoit Tessoulin, Steven Le Gouill, Amandine Lebourgeois, Cyrille Touzeau, Patrice Chevalier, Beatrice Mahe, Maxime Jullien, Alice Garnier, Sabrina Trudel, Nicolas Blin, and Thomas Gastinne
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Kaplan-Meier Estimate ,Single Center ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Refractory ,Recurrence ,Risk Factors ,Internal medicine ,medicine ,Humans ,Multiple myeloma ,Aged ,Retrospective Studies ,Aged, 80 and over ,Salvage Therapy ,Membrane Glycoproteins ,Hematology ,business.industry ,Antibodies, Monoclonal ,Daratumumab ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,ADP-ribosyl Cyclase 1 ,Progression-Free Survival ,Clinical trial ,Treatment Outcome ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Disease Progression ,Proteasome inhibitor ,Drug Evaluation ,Female ,Multiple Myeloma ,business ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
The anti-CD38 monoclonal antibody daratumumab is approved as a single agent for the treatment of patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMID), or who are double refractory to a PI and an IMID. To date, no real-life data on the efficacy and tolerance of daratumumab in this setting are available. We report here the results of a single-center series of 41 RRMM patients treated with single-agent daratumumab outside clinical trials. Patients received a median number of 4 prior therapies. All patients were previously exposed to PI and IMID and all patients were refractory to the last line of therapy. Most patients presented with high-risk characteristics, including 24% adverse cytogenetics (del17p/t(4,14)), 31% extramedullary disease and 12% circulating plasmacytosis at time of daratumumab therapy. The overall response rate was 24%, including 5% very good partial response or better. After a median follow-up of 6.5 months, all patients experienced disease relapse. The median progression-free survival was 1.9 months. At the time of disease progression, 44% of patients did not receive subsequent therapy. The median overall survival was 6.5 months. No new safety signal was identified. These real-life results revealed modest efficacy of single-agent daratumumab in advanced patients with RRMM in comparison with data from clinical trials.
- Published
- 2019
23. Autoimmune hypoglycemia expands the biological spectrum of HHV8(+) multicentric Castleman disease
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David Boutboul, Eric Oksenhendler, Claire Fieschi, Pierre Arnautou, Lionel Galicier, Jehane Fadlallah, Djaouida Bengoufa, Nicolas Blin, Soraya Fellahi, Corinne Vigouroux, Elias Barrak, Viviane Queyrel-Moranne, Martine Auclair, Laurence Gérard, Lucy Chaillous, Clara Bouché, Marion Malphettes, and Rémi Bertinchamp
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biology ,business.industry ,Castleman Disease ,Autoantibody ,nutritional and metabolic diseases ,Hematology ,Autoimmune hypoglycemia ,Stimulus Report ,Hypoglycemia ,Insulin receptor ,Insulin signal transduction pathway and regulation of blood glucose ,Immunology ,Herpesvirus 8, Human ,biology.protein ,Effective treatment ,Medicine ,Humans ,Rituximab ,Multicentric Castleman Disease ,Complication ,business ,medicine.drug - Abstract
Key Points Autoimmune hypoglycemia belongs to the clinical spectrum of HHV8+ MCD and rituximab is an effective treatment of this condition. This rare complication is related to autoantibodies directed toward the insulin receptor and activating the insulin signaling pathway.
- Published
- 2021
24. Interest of a third dose of BNT162b2 anti‐SARS‐CoV‐2 messenger RNA vaccine after allotransplant
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Philippe Moreau, Berthe-Marie Imbert, Thierry Guillaume, Steven Le Gouill, Marianne Coste-Burel, Thomas Gastinne, Amandine Le Bourgeois, Alice Garnier, Cyrille Touzeau, Maxime Jullien, Thomas Drumel, Nicolas Blin, Sophie Vantyghem, Benoit Tessoulin, Beatrice Mahe, Marie C. Béné, Anne Lok, Pierre Peterlin, Patrice Chevallier, Viviane Dubruille, Centre hospitalier universitaire de Nantes (CHU Nantes), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
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Adult ,Male ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) mRNA ,Antibodies, Viral ,Young Adult ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,vaccine ,Correspondence ,Medicine ,Humans ,Transplantation, Homologous ,BNT162 Vaccine ,ComputingMilieux_MISCELLANEOUS ,Aged ,Retrospective Studies ,Messenger RNA ,business.industry ,SARS-CoV-2 ,COVID-19 ,allogeneic haematopoietic stem cell transplantation ,Hematology ,Organ Transplantation ,Middle Aged ,Allografts ,Virology ,Antibody Formation ,severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA ,third dose ,coronavirus disease 2019 (COVID-19) ,Female ,BNT162b2 ,coronavirus disease 2019 (COVID‐19) ,business ,Stem Cell Transplantation - Abstract
International audience; No abstract available
- Published
- 2021
25. Time-dependent roles of adolescent- and adult-born dentate granule neurons in spatial learning
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Shaoyu Ge, Marie-Françoise Montaron, Nuria Masachs, Sophie Tronel, Valérie Lemaire, Nicolas Blin, Fanny Farrugia, Daniela Cota, Cyril Herry, Wilfrid Mazier, Djoher Nora Abrous, Véronique Deroche-Gamonet, Vanessa Charrier, INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, Institut National de la Santé et de la Recherche Médicale (INSERM), State University of New York (SUNY), tronel, sophie, Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), and Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM)
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0303 health sciences ,Dentate gyrus ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SDV]Life Sciences [q-bio] ,[SCCO.NEUR] Cognitive science/Neuroscience ,Cognition ,Biology ,Development ,03 medical and health sciences ,0302 clinical medicine ,Spatial memory ,nervous system ,Spatial learning ,Rat ,Optogenetic ,Neuroscience ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
SUMMARYThe dentate gyrus presents the peculiarity to be formed after birth in rodents. Adolescence is a very sensitive period during which cognitive competences are programmed. We investigated and compared the role of dentate neurons born during adolescence or generated during adulthood. We demonstrated that the ontogenetic stage of dentate neurons in relation to when they are generated dictates their participation in memory processes.
- Published
- 2020
26. Antithymocyte globulin administration in patients with profound lymphopenia receiving a PBSC purine analog/busulfan-based conditioning regimen allograft
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Soraya Wuilleme, Camille Debord, Steven Le Gouill, Yannick Le Bris, Alice Garnier, Philippe Moreau, Patrice Chevallier, Thomas Gastinne, Thierry Guillaume, Benoit Tessoulin, Beatrice Mahe, Viviane Dubruille, Nicolas Blin, Marie C. Béné, Marion Eveillard, Amandine Le Bourgeois, Alix Duquesne, Cyrille Touzeau, Maxime Jullien, and Pierre Peterlin
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Lymphocyte ,Graft vs Host Disease ,lcsh:Medicine ,Purine analogue ,Hematopoietic stem cell transplantation ,Disease-Free Survival ,Lymphocyte Depletion ,Article ,03 medical and health sciences ,0302 clinical medicine ,Lymphopenia ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Dosing ,lcsh:Science ,Adverse effect ,Busulfan ,Aged ,Antilymphocyte Serum ,Retrospective Studies ,Peripheral Blood Stem Cell Transplantation ,Multidisciplinary ,business.industry ,Stem-cell therapies ,lcsh:R ,Hematopoietic Stem Cell Transplantation ,Purine Nucleosides ,Middle Aged ,Allografts ,Transplantation ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Peripheral Blood Stem Cells ,Female ,lcsh:Q ,Immunotherapy ,business ,030215 immunology ,medicine.drug - Abstract
Graft-versus host disease (GVHD) remains one of the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (ASCT). Prophylactic T cell depletion via antithymocyte globulin (ATG) during ASCT conditioning is one of the standards of care for GVHD prophylaxis, although the optimal dosing strategy is still unclear. Recent studies have reported that absolute lymphocyte count at the time of ATG administration could predict survivals in ASCT from unrelated donors. Here this issue was examined in 116 patients receiving peripheral blood stem cells (PBSC) ASCT with purine analog/busulfan-based conditioning regimens between 2009 and 2019 in our department. The impact of lymphopenia at the time of ATG administration was evaluated in terms of overall survival, disease-free survival and GVHD-free/relapse-free survival. After a median follow-up of 4 years, no adverse effect of a profound lymphopenia was observed on patients’ outcome. Notably, a reduced dose of ATG in patients with profound lymphopenia did not translate into better survivals. This study indicates that ATG can be administered whatever the recipient’s lymphocyte counts in patients receiving a PBSC purine analog/busulfan-based conditioning regimen ASCT.
- Published
- 2020
27. Randomized Trial Comparing Double Versus Triple Bortezomib-Based Regimen in Patients With Multiple Myeloma and Acute Kidney Injury Due to Cast Nephropathy
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Vincent Audard, Felipe Suarez, Salomon Manier, Frank Bridoux, Cécile Vigneau, Karine Augeul-Meunier, Bertrand Joly, Lionel Karlin, Bertrand Arnulf, Mourad Tiab, Nina Arakelyan-Laboure, Sophie Caillard, Alexandre Karras, Nolwenn Rabot, K. Belhadj, Bruno Royer, Margaret Macro, Sébastien Delbès, Jean Paul Fermand, P. Gobert, Damien Roos-Weil, Brigitte Pegourie, Emilie Cornec-Le Gall, Sylvie Chevret, Nicolas Blin, Denis Caillot, and Arnaud Jaccard
- Subjects
0301 basic medicine ,Male ,Cancer Research ,medicine.medical_specialty ,Urology ,Dexamethasone ,Nephropathy ,law.invention ,Bortezomib ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,In patient ,Myeloma cast nephropathy ,Cyclophosphamide ,Multiple myeloma ,Aged ,business.industry ,Acute kidney injury ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,Regimen ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,business ,Multiple Myeloma ,medicine.drug - Abstract
PURPOSE We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and acute kidney injury (AKI) without need for dialysis. METHODS After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light chains (sFLCs) after 3 cycles, chemotherapy was reinforced with either cyclophosphamide (BD group) or thalidomide (C-BD group). RESULTS Ninety-two patients were enrolled in each group. At random assignment, characteristics of the 2 groups were similar, including median age (68 years) and serum creatinine level (305.5 and 273.5 µmol/L in BD and C-BD group, respectively). At 3 months, renal response rate (primary end point) was not different (41 v 47 responders in the BD and C-BD groups, respectively; relative risk [RR], 0.87; P = .46). Very good partial response (free light chain reduction ≥ 90%) or more was achieved in 36 and 47 patients, respectively (RR, 0.76; P = .10). After 1 cycle of chemotherapy, 69 in the BD group and 67 patients in the C-BD group had achieved sFLC level ≤ 500 mg/L. Serious adverse events were recorded in 30 and 40 patients, respectively. At 12 months, 19 patients had died (9 in the BD group v 10 in the C-BD group), including 10 (6 in the BD group and 4 in the C-BD group) from myeloma progression and 3 (0 in the BD group and 3 in the C-BD group) from infection. Within median follow-up of 27 months, 43 and 42 patients switched to new therapy, respectively. Overall, 50 patients (24 in the BD group and 26 in the C-BD group) had died. CONCLUSION This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial CN not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty.
- Published
- 2020
28. Coping Strategies and Factors Related to Problematic Substance Use and Behavioral Addictions Among Adolescents and Young Adults with Cancer
- Author
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E. Seigneur, Tanguy Leprince, Kristopher Lamore, Nadège Corradini, Perrine Marec-Berard, Daniela Silva Moura, Valérie Laurence, Cécile Flahault, Nicolas Blin, Solène Grégoire, and Sophie Chauvet
- Subjects
Adult ,Male ,Behavioral addiction ,Coping (psychology) ,Adolescent ,Substance-Related Disorders ,media_common.quotation_subject ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Adaptation, Psychological ,medicine ,Humans ,030212 general & internal medicine ,Cannabis Dependence ,media_common ,Alcohol Use Disorders Identification Test ,biology ,business.industry ,Addiction ,biology.organism_classification ,medicine.disease ,humanities ,Behavior, Addictive ,Eating disorders ,Oncology ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Anxiety ,Female ,Cannabis ,medicine.symptom ,business ,Clinical psychology - Abstract
Purpose: This study aimed to explore and identify the factors associated with problematic substance use (alcohol, tobacco, and cannabis) and behavioral addictions (internet and eating disorders) over time in adolescents and young adults (AYAs) treated for cancer. Methods: AYAs newly diagnosed with cancer, 15-25 years of age, completed a questionnaire during their hospitalization (T1), assessing their consumption of alcohol, tobacco, and cannabis (The Alcohol Use Disorders Identification Test; The Smoking Behavior Questionnaire; and The Cannabis Abuse Screening Test), their internet use (The Internet Addiction Test), their body preoccupations (The Eating Attitudes Test), as well as their coping strategies (Brief COPE) and emotional adjustment (The Hospital Anxiety and Depression Scale). Questionnaires were completed again 6 months later (T2). Results: Seventy-three AYAs were included at T1 and 21 AYAs at T2. Nearly one out of two (46.58%) AYAs had a problematic substance use or behavioral addiction after cancer diagnosis (T1). Problematic use of internet was frequently reported (23.29%), as well as harmful alcohol consumption or addiction (16.44%) and cannabis dependence (12.33%). The main factor related to problematic substance use was being older, while the main factor related to behavioral addiction was having a higher anxiety score. Substance use as a coping strategy was used more frequently by AYAs with problematic substance use and emotional support as a coping strategy was used more frequently by AYAs with a behavioral addiction. Conclusions: High rates of problematic substance use and behavioral addiction were reported in our sample. AYAs surveyed had high problematic use of cannabis and high internet use. Attention to substance use and addictive behaviors is recommended to ensure optimal care.
- Published
- 2020
29. Progression of disease within 2 years (POD24) is a clinically relevant endpoint to identify high-risk follicular lymphoma patients in real life
- Author
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Amandine Le Bourgeois, Patrice Chevallier, Philippe Moreau, Christophe Leux, Benoit Tessoulin, Steven Le Gouill, Thierry Guillaume, Beatrice Mahe, Clara Sortais, Cyrille Touzeau, Thomas Gastinne, Anne Moreau, Anne Lok, Alice Garnier, Pierre Peterlin, Viviane Dubruille, Nicolas Blin, Céline Bossard, Bernardo, Elizabeth, Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d’Anatomopathologie [CHU Nantes], Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Département de l'Information Médicale [CHU Nantes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
- Subjects
Male ,Oncology ,Time Factors ,Follicular lymphoma ,Cohort Studies ,0302 clinical medicine ,Recurrence ,Risk Factors ,Prednisone ,Antineoplastic Combined Chemotherapy Protocols ,Lymphoma, Follicular ,Aged, 80 and over ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,3. Good health ,Treatment Outcome ,Vincristine ,030220 oncology & carcinogenesis ,Cohort ,Disease Progression ,Female ,Rituximab ,France ,medicine.drug ,Adult ,medicine.medical_specialty ,Cyclophosphamide ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Predictive Value of Tests ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Aged ,Retrospective Studies ,business.industry ,medicine.disease ,Survival Analysis ,Lymphoma ,Clinical trial ,Doxorubicin ,Neoplasm Grading ,business ,030215 immunology - Abstract
International audience; Follicular lymphoma (FL) is an indolent non-Hodgkin's lymphoma with heterogeneous outcomes. Progression or relapse of FL within 2 years (so-called POD24) after diagnosis is associated with a poor outcome for patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) in clinical trials. POD24 needs further validation before it can be used as a relevant endpoint to assess treatment efficacy. In the present retrospective monocentric study, we investigated the predictive value of POD24 in a cohort of grade 1, 2, or 3a FL patients treated in our institution (Nantes Medical University, France) and registered in our local database. We investigated the nature of treatment lines, patients' outcomes, and the prognostic value of POD24. Between 2007 and 2016, 317 patients were included. After first-line therapy, 60 patients relapsed within 2 years (POD24-pos cohort), and 254 patients did not relapse within 2 years (PO24-neg cohort). Thirty-three patients died, and 34 patients had an aggressive transformation. The median follow-up is 59.9 months (1.6-395.5). The median PFS is 59.9 months. Overall survival (OS) at 1 year, 3 years, and 5 years is 98.4% [97.0-99.8], 95.1% [92.6-97.6], and 92.5% [89.3-95.9], respectively. The 5-year OS was statistically lower for POD24-pos patients (82% [71.9-93.5]) than for POD24-neg patients (93.3% [88.98-97.8]) (p = 10-5). In multivariate analyses, transformation was predictive of OS, and PS (≥ 1) was predictive of POD24. POD24 is predictive of a worse OS and may be recommended as a relevant endpoint in clinical trials and in real life in particular for patients with advanced disease.
- Published
- 2020
30. RASmutation leading to acquired resistance to dabrafenib and trametinib therapy in a multiplemyeloma patient harboring BRAF mutation
- Author
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Philippe Moreau, Steven Le Gouill, Baptiste Le Calvez, Olivier Theisen, Nicolas Blin, Guillaume Herbreteau, Françoise Kraeber-Bodéré, Thomas Gastinne, Benoit Tessoulin, Chloé Antier, Céline Bossard, Yannick Le Bris, Cyrille Touzeau, Marie C. Béné, Viviane Dubruille, Bastien Jamet, Beatrice Mahe, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Hématologie Biologique [Hôpital Hôtel-Dieu, Nantes], Hôpital Hôtel-Dieu [Nantes] (Centre Hospitalier Universitaire de Nantes), Département de Biochimie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Nord Laennec [CHU Nantes], Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Imaging and Longitudinal Investigations to Ameliorate Decision-making [Nantes] (ILIAD), Site de Recherche Intégrée sur le Cancer [Nantes] (SIRIC), Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de Pathologie [CHU Nantes], Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Nuclear Oncology (CRCINA-ÉQUIPE 13), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
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Neuroblastoma RAS viral oncogene homolog ,endocrine system diseases ,medicine.medical_treatment ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Targeted therapy ,BRAF ,03 medical and health sciences ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,medicine ,dabrafenib ,neoplasms ,Multiple myeloma ,030304 developmental biology ,Trametinib ,0303 health sciences ,trametinib ,Bortezomib ,business.industry ,Daratumumab ,Dabrafenib ,Pomalidomide ,medicine.disease ,digestive system diseases ,3. Good health ,multiple myeloma ,030220 oncology & carcinogenesis ,Cancer research ,business ,medicine.drug ,RAS - Abstract
International audience; Multiple myeloma (MM) is still considered incurable and new therapeutic approaches are therefore needed. Deep-sequencing analysis revealed the presence of BRAF mutations in up to 15% of patients. The clinical experience of BRAF-targeted therapy in myeloma patients harboring BRAF mutation is still limited. We here report the case of a patient with penta-refractory (bortezomib, lenalidomide, carfilzomib, pomalidomide, and daratumumab) MM with extramedullary BRAF-mutated disease that achieved clinical response to dual BRAF and MEK inhibition. At the time of disease progression, gene sequencing analysis of the tumor at the time of progression demonstrated a clonal evolution with emergence of aNRAS mutation and persistence of BRAF and TP53 mutations. Backtracking of the NRAS mutation was performed by digital polymerase chain reaction on the baseline biopsy and identified the pre-existence of the NRAS at a subclonal level. This observation is the first report of acquired NRAS mutation leading to resistance to dual BRAF/MEK inhibitors in MM. These data suggest that a systematic search for RAS mutations using highly sensitive techniques should be performed before considering targeted therapy in relapsed myeloma with BRAF mutation.
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- 2020
31. Clofarabine-based reduced intensity conditioning regimen with peripheral blood stem cell graft and post-transplant cyclophosphamide in adults with myeloid malignancies
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Philippe Moreau, Nicolas Blin, Thierry Guillaume, Alice Garnier, Cyrille Touzeau, Beatrice Mahe, Steven Le Gouill, Patrice Chevallier, Thomas Gastinne, Anne Lok, Pierre Peterlin, Viviane Dubruille, Marie C. Béné, Yannick Le Bris, and Amandine Le Bourgeois
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haplo-identical ,medicine.medical_specialty ,Myeloid ,Cyclophosphamide ,post-transplant cyclophosphamide ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Clofarabine ,allogeneic ,Hematology ,business.industry ,Myeloid leukemia ,Fludarabine ,Transplantation ,Regimen ,medicine.anatomical_structure ,Oncology ,clofarabine ,030220 oncology & carcinogenesis ,PBSC ,business ,Research Paper ,030215 immunology ,medicine.drug - Abstract
// Patrice Chevallier 1 , Pierre Peterlin 1 , Alice Garnier 1 , Amandine Le Bourgeois 1 , Beatrice Mahe 1 , Viviane Dubruille 1 , Nicolas Blin 1 , Cyrille Touzeau 1 , Thomas Gastinne 1 , Anne Lok 1 , Yannick Le Bris 2 , Marie C. Bene 2 , Steven Le Gouill 1 , Philippe Moreau 1 and Thierry Guillaume 1 1 Hematology Department, CHU Hotel-Dieu, Nantes, France 2 Hematology/Biology Laboratory, CHU Hotel-Dieu, Nantes, France Correspondence to: Patrice Chevallier, email: patrice.chevallier@chu-nantes.fr Keywords: allogeneic; clofarabine; post-transplant cyclophosphamide; haplo-identical; PBSC Received: June 11, 2018 Accepted: August 04, 2018 Published: September 11, 2018 ABSTRACT Background: The Baltimore reduced-intensity conditioning (RIC) regimen using high-dose post-transplant cyclophosphamide (PTCY) is considered as a standard of care for haploidentical allogeneic stem cell transplantation (allo-SCT). However, it is associated with relatively low survivals and high incidence of relapse, especially when considering myeloid malignancies. Results: This retrospective study included 36 adults (males n = 18; median age: 60.5 years old; haplodonors n = 27; matched donors n = 8) with myeloid malignancies transplanted between March 2014 and March 2017 at the University Hospital of Nantes. Very encouraging results were observed with a 18-month overall survival (OS), disease-free survival (DFS) and relapse incidence (RI) of 72% ± 7.5%, 63.8 ± 8%, and 25 ± 6% respectively, and a GVHD relapse-free survival (GRFS) of 52.6 ± 8%. In univariate analysis, there were no differences regarding 18-month survivals between patients allografted: i) for acute myeloid leukemia vs myelodysplastic syndrome (OS 70 ± 11% vs 69.2 ± 13%, p = 0.3; DFS 64.7 ± 11% vs 61.5 ± 13%, p = 0.65), or ii) with haplo-identical vs other donors (OS: 66.2 ± 9% vs 88.8 ± 10.4%, p = 0.16; DFS 59 ± 9.5% vs 77.8%, p = 0.6). Conclusion: The “Clo-Baltimore regimen” is safe and feasible and provides good survivals for patients with myeloid malignancies and haplo-donors. Methods: Here, we report a variant of the Baltimore regimen, where 1) fludarabine was replaced by clofarabine, 2) bone marrow was replaced by peripheral blood stem cells, and 3) tacrolimus was replaced by cyclosporine, in a “Clo-Baltimore regimen”.
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- 2018
32. Interest of a Third Dose of BNT162b2 Anti- Sars-Cov-2 mRNA Vaccine in Allogeneic Hematopoietic Stem-Cells Recipients
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Amandine Le Bourgeois, Thierry Guillaume, Berthe-Marie Imbert, Patrice Chevallier, Nicolas Blin, Philippe Moreau, Cyrille Touzeau, Thomas Drumel, Benoit Tessoulin, Marie C. Béné, Steven Le Gouill, Beatrice Mahe, Anne Lok, Thomas Gastinne, Sophie Vantyghem, Pierre Peterlin, Viviane Dubruille, Alice Garnier, Marianne Coste-Burel, and Maxime Jullien
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Messenger RNA ,Haematopoiesis ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Medicine ,Cell Biology ,Hematology ,Stem cell ,business ,Biochemistry ,Virology ,722.Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution - Abstract
Introduction In a previous observational study of 117 allogeneic hematopoietic stem cell transplant (Allo-HSCT) recipients, we found that 83 % of them achieved a specific humoral response after two doses (V1 and V2) of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine (Pfizer BioNTech). However, although 61.5% of the patients achieved the highest detectable IgG titers, this proportion remained significantly lower than what was observed in healthy controls, where 100% reached these highest antibody titers. Here, we investigated whether a third dose of vaccine would improve the anti- SARS-CoV-2 response in Allo-HSCT recipients. Methods This monocentric retrospective study aimed at evaluating the efficacy of a third vaccine (V3) of BNT162b2 in a cohort of Allo-HSCT adult recipients. Patients with previous clinical or asymptomatic biological COVID-19 infection at V1 were excluded from the study. A cohort of healthy volunteers (caregivers from the Clinical Hematology Department) who had also already received V1 and V2 was considered as controls. All participants were vaccinated between January 20 and June 1, 2021. Analyses were performed in July 2021. Antibody response to the SARS-CoV-2 spike protein receptor-binding domain was tested after V2 for all subjects (Serology post V2, SpV2) using the Roche Elecsys® assay. All subjects benefited later from another evaluation of specific serum antibodies as monitoring (Serology post V2+, SpV2+) or after V3 (Serology post V3, SpV3). Various serological methods were used for these later assays because performed outside of our hospital for some patients. Considering thresholds of negativity and positivity as well as highest values for each test, we were able nevertheless to distinguish 4 sub-groups: i) negativity at both SpV2 & SpV2+/SpV3, ii) increase of the IgG titer between SpV2 & SpV2+/SpV3, including patients showing seroconversion, iii) decreased or stable IgG titer between SpV2 & SpV2+/SpV3 and iv) highest IgG titers at both SpV2 and SpV2+/SpV3. Results A cohort of 25 controls and 114 patients, including 91 who received V3 (V3+) and 23 who did not (V3-) was considered for the purpose of this study. The characteristics of participants and delays from SpV2 to SpV2+ or SpV2 to SpV3 are reported in Tables 1 and 2. The serological methods used for the latest assays are reported in Table 2 with criteria of negativity, positivity and highest IgG titer values. V3- patients were younger, with less myeloid disease than V3+ cases and had not received myeloablative conditioning. However, both V3+ and V3- groups shared similar median intervals between Allo-HSCT and V1, incidence of previous graft versus host disease (GVHD), proportions of patients under chemotherapy or immunosuppressive drugs and median lymphocyte counts at V1, suggesting similar immune status. The reasons for not receiving V3 were forgetting, refusal or surveillance after detection of the highest IgG titer at SV2. Samples from controls, all evaluated by Roche Elecsys®, showed the highest anti-spike antibody value (>250U/mL) at both SpV2 and SpV2+, suggesting a persistent response without the need of a third vaccine in this healthy population. The proportion of patients still negative at SpV2+/SpV3 was similar between V3- and V3+ patients (17% vs 12%, p=0.74). However, the proportion of patients showing a decreased/stable IgG titer between SpV2 and SpV2+/SpV3 was significantly higher for V3- cases (35% vs 4%, p=0.0001) (Table 2). Moreover, the proportion of patients with the highest IgG titer at SpV2+/SpV3 was significantly higher in the V3+ sub-group (80% vs 43%, p=0.001), even if it remained significantly lower than in controls (p=0.03). The proportion of patients showing an IgG titer increase between SpV2 and SpV2+/SpV3 was higher in V3+ vs V3- patients (24% vs 4%, p=0.06). The difference was not significant as surprisingly one V3- case showed a seroconversion without any argument for SARS-CoV-2 infection between SpV2 and SpV2+. Three patients out of 14 (21%), with a negative SpV2, showed a seroconversion after V3. Finally, with a median follow up from V1 of 106 days in V3+ patients, 138 days in V3- patients and 154 days in controls, no COVID-19 infection was documented in any participant. Conclusion This study shows the interest of a third dose of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine after allograft as more patients are documented with less decrease of IgG titers and the highest IgG values after V3. Figure 1 Figure 1. Disclosures Moreau: Abbvie: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Celgene BMS: Honoraria; Oncopeptides: Honoraria.
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- 2021
33. Sars-Cov-2 T-Cell Response in Allogeneic Hematopoietic Stem Cell Recipients Following Two Doses of BNT162b2 Vaccine
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Philippe Moreau, Marie C. Béné, Jocelyn Ollier, Patrice Chevallier, Benoit Tessoulin, Berthe-Marie Imbert, Cyrille Touzeau, Steven Le Gouill, Thierry Guillaume, Viviane Dubruille, Beatrice Mahe, Marianne Coste-Burel, Thomas Gastinne, Alice Garnier, Nicolas Blin, Henri Vié, Amandine Le Bourgeois, Anne Lok, Pierre Peterlin, Sophie Vantyghem, Maxime Jullien, Thomas Drumel, and Béatrice Clémenceau
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medicine.anatomical_structure ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Medicine ,Hematopoietic stem cell ,Cell Biology ,Hematology ,T cell response ,business ,Biochemistry ,Virology ,722.Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution - Abstract
Introduction: Virus-specific humoral and cellular immune responses act synergistically to protect from viral infection. In our recent observational monocentric study of 117 hematopoietic stem cell adult recipients, we found that 54% and 83 % patients achieved a humoral response after two doses of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine (Pfizer BioNTech), respectively. Here, we evaluated the T-cell response against the SARS-Cov-2 spike protein after two doses of BNT162b2 vaccine in some allografted patients from the same cohort and compared these results to those from healthy controls. Methods: To quantify SARS-CoV-2 specific T-cells, we used an INFg ELISpot assay that detects these cells after activation of peripheral blood mononuclear cells (PBMC) with 3 peptide pools covering the whole protein sequence of the spike glycoprotein (Prot _S1; _S+ and _S PepTivator peptide pools, Miltenyi Biotec, Bergisch Gladbach, Germany). EBV and CMV specific T-cells were also quantified as controls. The immunophenotype of PBMC was determined by flow cytometry, after dead cell exclusion, with monoclonal antibodies identifying the following surface antigens: CD45, CD3, CD14, CD19 and HLA-DR. The frequencies of spot-forming units (SFU) were reported as per 10 6 CD3+ T-cells. Results: Samples from 46 allografted patients (acute myeloblastic leukemia, N=27, myelodysplastic syndrome, N=19) and 16 healthy controls were available. Characteristics of the population are given in Table 1. All fully vaccinated healthy donors became seropositive and developed a positive T-cell response to spike peptide pools even though variable frequencies were observed. The median response was 195 SFU/10 6 T-cells. By comparison, the frequency of EBV-specific T-cells was 774 SFU/10 6 T-cells (Figure 1). In the group of patients, 78% (n=36/46) had achieved a humoral response after the second dose of vaccine. Among these humoral responders (HR), 89% (n=32/36) also had a positive anti-spike T-cell response with variable frequencies (median =119 SFU/10 6 T-cells. For 8 patients, this T cell response was higher than that of controls (>800 SFU/10 6 T-cells) (Figure 1), which is equivalent to more than 1 specific T-cell per microliter of blood (Figure 2). The humoral responders (HR) who did not develop a T-cell response (11%, n=4/36) had a median time from transplant to vaccination of 523 days compared to 1032 days for cellular responder patients. Among the 10 patients who were non humoral responders (NHR) (22%, n=10/46), 4 (40%) developed a cellular immunity, including one with a very high T cell response (1333 SFU/10 6 T-cells). As expected, the absence of humoral response was observed in patients who were within one year of the transplant. Of note, somehow unexpectedly, patients often presented a high frequency of EBV- and CMV-specific T cells (Figures 1 & 2). As expected, PBMC immunophenotypic analysis revealed that CD3+ frequencies were lower in patients compared to those of controls but were similar between HR and NHR. NHR had very low frequencies of B cells and interestingly, they had an elevated frequency of CD14+ monocytes with low/neg HLA-DR expression potentially corresponding to myeloid-derived suppressor cells (MDSCs) (Figure 3). Conclusion: In this series, 89% of allografted patients who developed an anti-spike humoral response also presented an anti-SARS-Cov-2 cellular immunity. Interestingly, anti-SARS-Cov-2 specific T-cells could be detected in 40% of NHR patients. Although a larger group of patients is required to confirm these results, it remains to be determined whether this T-cell response is protective against SARS-Cov-2 infection as previously demonstrated for CMV (Litjens et al, 2017). Finally, the role of potential immunosuppressive MDSCs must be explored in patients who develop no sign of T-cell response after vaccination. Figure 1 Figure 1. Disclosures Moreau: Oncopeptides: Honoraria; Celgene BMS: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Amgen: Honoraria.
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- 2021
34. Profound B-Cell Lymphopenia Is a Major Factor Predicting Poor Humoral Response after BNT162b2 mRNA Sars-Cov-2 Vaccines in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
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Marie Rimbert, Cyrille Touzeau, Berthe Marie Imbert, Thierry Guillaume, Beatrice Mahe, Alice Garnier, Nicolas Blin, Marie C. Béné, Steven Le Gouill, Marianne Coste-Burel, M. Audrain, Amandine Le Bourgeois, Patrice Chevallier, Benoit Tessoulin, Viviane Dubruille, Philippe Moreau, Thomas Drumel, Sophie Vantyghem, Thomas Gastinne, Anne Lok, Pierre Peterlin, and Maxime Jullien
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Messenger RNA ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine.medical_treatment ,Immunology ,B-cell lymphopenia ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Biochemistry ,722.Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution ,Medicine ,business - Abstract
Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection results in poor outcome in patients with hematologic malignancies. Moreover, the efficacy of anti-SARS-CoV-2 mRNA vaccines appears lower in immunocompromised patients, including recipients of allogeneic stem cell transplantation (Allo-HSCT). In this population, data are scarce regarding factors predicting the response to mRNA vaccines. Methods This retrospective study aimed to decipher which factors, including immune status at time of vaccine and recipient/donor blood groups, might influence the antibody response after two injections (V1 and V2) of BNT162b2 (Pfizer-BioNTech) vaccine in a cohort of allografted patients with no previous symptomatic nor asymptomatic COVID-19 infection. Possible previous asymptomatic COVID-19 infection was investigated in pre-V1 samples by testing for anti-nucleocapsid (N) antibodies (anti-SARS-CoV-2 immunoassay, Roche Elecsys®, Rotkreuz, Switzerland). Antibody response to the SARS-CoV-2 spike protein receptor-binding domain was tested post-V2 (Roche Elecsys®). As recommended by the manufacturer, titers ≥0.8 U/mL were considered positive, the highest value being >250 U/mL. Blood samples were also collected before V1 and at distance from V2 to evaluate, by flow cytometry, total lymphocyte (Ly) counts and quantitative Ly subsets (CD3, CD4 and CD8 T cells, B and NK cells). Statistical analyses were performed on R (version 4.0.3). Patient characteristics were compared by using the Χ² test for discrete variables and the Wilcoxon test for continuous variables. Generalized linear models were used to conduct multivariate analyses. Results Samples were available from 117 Allo-HSCT patients who had been vaccinated between January 20 and April 17, 2021. Patient characteristics are provided in Table 1. The average interval from Allo-HSCT day 0 (D0) to V1 (D0-V1) was 654 (IQR: 372-1367) days (d). S-antibody response rate post-V2 was 82.9% for the entire cohort. Non-humoral responders (NHR) post-V2 (n = 20) had a lower D0-V1 interval (median 271 vs 914 d, p The possible modification in terms of lymphocyte counts between pre-V1 and post-V2 times has been also investigated showing that only CD4 lymphocytes counts improved significantly (0.31 vs 0.34 x10 9/L, p=0.01) between this interval. Conclusion B cell aplasia appears as a major predictor of anti SARS-CoV-2 mRNA vaccine failure after Allo-HSCT. It may be suggested from this result that a close immune monitoring should be proposed after allotransplant to propose the vaccine at the most appropriate time, meaning after of B cell detection, regardless of the delay from Allo-SCT or the presence of an IS/chemotherapy treatment. The possibility for these patients to have mounted a cellular response should also be considered, which was not investigated here. Figure 1 Figure 1. Disclosures Moreau: Celgene BMS: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria; Oncopeptides: Honoraria; Amgen: Honoraria; Janssen: Honoraria.
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- 2021
35. Antibody Response after One and/or Two Doses of BNT162b2 Anti- Sars-Cov-2 mRNA Vaccine in Patients Treated By CAR T-Cells Therapy
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Philippe Moreau, Berthe-Marie Imbert, Thomas Gastinne, Marianne Coste-Burel, Sophie Vantyghem, Beatrice Mahe, Marie C. Béné, Anne Lok, Thomas Drumel, Pierre Peterlin, Viviane Dubruille, Patrice Chevallier, Benoit Tessoulin, Nicolas Blin, Steven Le Gouill, Cyrille Touzeau, Amandine Le Bourgeois, Maxime Jullien, Alice Garnier, and Thierry Guillaume
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704.Cellular Immunotherapies: Clinical ,Messenger RNA ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Virology ,Antibody response ,Medicine ,In patient ,Car t cells ,business - Abstract
Introduction: Data regarding the efficacy of anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) messenger RNA vaccines in immunocompromised hosts are scarce and no data yet appear to be available for patients with hematological malignancies who also received chimeric antigen receptor-T (CAR-T) cells therapy. Methods: The efficacy and safety of one and/or two injections of the BNT162b2 (Pfizer-BioNTech) vaccine was evaluated retrospectively in 23 CAR-T recipients in our Hematology Department, compared to a cohort of 25 healthy caregivers, vaccinated concomitantly between January 28 and May 31, 2021. None of these individuals had a previous clinical history of COVID-19. Results: Overall, the patients (14 males and 9 females) had a median age of 62 years old (range: 21-79) and had received CAR-T for high-grade lymphoma (n= 20) or acute lymphoblastic leukemia (n= 3). Eight and 3 had been respectively previously autografted or allografted and two were allografted after CAR-T. All patients were pretreated for lymphodepletion by fludarabine + cyclophosphamide before CAR-T infusion. The CAR-T provided were axicabtagene ciloleucel (Yescarta, Kite/Gilead, n=16, tisagenlecleucel (Kymriah, Novartis Pharma, n=5 and brexucabtagene autoleucel (KTE-X19, Tecartus, Kite/Gilead, n=1). One additional patient received allogeneic UCART19 (Servier). The median delay between CAR-T administration and the first vaccine (V1) was 401 days (d; range: 113-819). All patients but 2 were in complete remission at V1 and 3 were still on therapy (revlimid n=1, tafasitamab n=1, chemotherapy n=1). After V1, antibody response to the SARS-CoV-2 spike protein receptor-binding domain was tested by the Roche Elecsys® assay at a median time of 29 d (range: 16-32) in 19 patients and 23 d (range:18-32) in controls. At that time, only 4/23 patients (21%) but all controls (100%) had a positive anti-spike antibody response (p250) than in patients (5.9 U/mL range 4.1-41.6, p=0.06). The highest IgG titer (>250) was obtained in 2 controls. The median delay between V1 and the second vaccine (V2) was 28 d (range: 14-46) for patients and 23 d (range: 18-32) for controls. Among the 20 patients tested after V2, 17 had also been tested after V1 while 3 were tested only after V2. All controls were tested after V2. The second serology assay was performed at a median interval from V2 of 52 d (range: 21-99) for patients and 58 d (range: 32-71) for controls. This serology assay was positive in 6 patients (30%), while all controls (100%, p250) after V2. The two patients in relapse and treated by chemotherapy or tafasitamab did not develop antibodies after V2 conversely to the patient under maintenance by revlimid. The delay between CAR-T infusion and vaccine did not influence the antibody response nor did the rate of lymphopenia as almost all patients remained under a lymphocyte threshold of 1x10 9/L. Finally, with a median follow up from V1 of 77 d (range: 49-127) in patients and 81 d (range: 62-95) in controls, no COVID-19 infection has been documented in any of these participants. Conclusion: This study shows that the administration of two doses of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine provides a low rate of seroconversion (30%) in recipients of CAR-T therapy. This is likely related to the profound B-cell depletion induced by this treatment precisely targeting CD19+ cells. Investigation of the development of specific T-cell responses in these individuals could provide more information about the efficacy of vaccination in this context. Disclosures Moreau: Celgene BMS: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Oncopeptides: Honoraria.
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- 2021
36. Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia: Why Do Adolescents and Young Adults Outcomes Differ from Those of Children? a Study on Behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)
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Yves Bertrand, Nicolas Blin, Lucie Planche, Virginie Gandemer, Natacha Maillard, Fanny Rialland, Jacques-Olivier Bay, Charlotte Jubert, Audrey Grain, Pierre-Simon Rohrlich, Nathalie Dhedin, Patrice Chevallier, Dominique Plantaz, Régis Peffault de Latour, Anna Berceanu, Catherine Paillard, Cécile Pochon, Anne Sirvent, Edouard Forcade, André Baruchel, Gérard Michel, Ibrahim yakoub Agha, Pascale Schneider, Stephanie Nguyen Quoc, Eolia Brissot, Jean-Hugues Dalle, and Fanny Gonzales
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Oncology ,medicine.medical_specialty ,business.industry ,Lymphoblastic Leukemia ,medicine.medical_treatment ,Immunology ,Cell Biology ,Hematology ,Hematopoietic stem cell transplantation ,Biochemistry ,humanities ,Transplantation ,Cell therapy ,Internal medicine ,Medicine ,Young adult ,Stem cell ,business - Abstract
Introduction: Adolescents and Young Adults (AYA) represent a specific population in the Acute Lymphoblastic Leukemia (ALL) landscape, often presenting high-risk diseases and increased chemotherapy-related toxicities. Indications of Hematopoietic Stem Cell Transplantation for pediatric patients (HSCT) have been restricted to those with early poor response to chemotherapy. The same trend has led to a decrease of HSCT indications in AYAs, which are nevertheless still more frequent than in younger counterpart. Outcomes of AYAs after HSCT seemed to be worse than the ones of children in two previous studies published in 2013 and 2014. In Minneapolis, the decrease of overall survival in AYA was attributed to an excess of Treatment Related mortality (TRM) (28% versus 14%; p=0.04), but because of small numbers, factors influencing TRM were not identified. Our study aimed to compare, in a large cohort, the outcomes of children and AYA with ALL after HSCT and to determine factors influencing potential differences. Material and Methods: All patients aged between 1 and 25 years, reported in the SFGM-TC (Francophone Society of bone marrow transplantation and cellular therapy) registry, who received a first HSCT in treatment for ALL between 2005 and 2012 were included. The AYA group was defined by age range between 15 and 25 years old, according to European studies and the SFGM-TC. Data about diagnosis and transplantation procedure were prospectively collected in the registry. Before transplant procedure, patients or their parents/guardians provide a signed consent in order to be included in the registry. Results: 891 patients were included, 494 children and 397 AYA. Median time of follow up was 45.6 months (0 to 114). HSCT was performed in first CR for 56.8% of the AYAs, whereas 57.5% of children received HSCT in second CR or more advanced phase (p Five-year OS was lower in AYA 53.1% versus 64% (p = 0.0012) and we confirmed higher 5-years TRM in AYA 19% versus 13% (p=0.04). TRM incidence markedly rose after 10 years of age (from 9% before 10 years old to 20% between 10 and 15 years, and 17% after 15 years). Graft versus host disease and Relapse Free Survival probability (GRFS) was lower in AYA: 36% versus 47% (p=0.007), while Cumulative Incidence of Relapse (CIR) and acute Graft versus Host Disease (GvHD) incidence were both similar in our two groups: 32% and 61% in AYAs versus 27% and 59% in children, (p=0.19 and p=0.62), respectively. Thus, chronic GvHD, which occurred more frequently in AYA than in children (32% versus 19%, p In our multivariate analysis, two factors were associated with higher risk of cGvHD: use of PBSC as stem cell source (HR 1.41 [0.96-2.07], p=0.083), and absence of ATG use (HR associated with use of ATG: 0.62 [0.42-0.92], p=0.017) (Figure 3). Of note a subgroup analysis in patients who received a bone marrow transplant after a MAC, showed no TRM difference between AYA and children. Conclusion: AYA or patients aged more than 10 years, compared to ones aged less than 10 years have a worse outcome after HSCT for ALL. Excess of death in this specific population is mainly due cGvHD. Transplantation practices in those patients, particularly choice of stem cells source and GvHD prophylaxis, should be discussed. Their treatment adherence should also be questioned and reinforced by development of multidisciplinary teams. Figure 1 Figure 1. Disclosures Peffault De Latour: Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Amgen: Consultancy, Other, Research Funding; Jazz Pharmaceuticals: Honoraria; Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Forcade: Novartis: Other: travel grant.
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- 2021
37. A Prospective Phase 2 Study Testing High Dose Post-Transplant Cyclophosphamide As Sole Ghvd Prophylaxis after Matched Allotransplant Using Baltimore-Based Reduced-Intensity Conditioning Regimens and PBSC As Source of Graft
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Sophie Vantyghem, Amandine Le Bourgeois, Thomas Gastinne, Patrice Chevallier, Benoit Tessoulin, Philippe Moreau, Marie C. Béné, Marion Eveillard, Steven Le Gouill, Yannick Le Bris, Viviane Dubruille, Beatrice Mahe, Cyrille Touzeau, Thierry Guillaume, Anne Lok, Alice Garnier, Pierre Peterlin, Maxime Jullien, and Nicolas Blin
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medicine.medical_specialty ,surgical procedures, operative ,Post transplant cyclophosphamide ,business.industry ,Reduced Intensity Conditioning ,Immunology ,medicine ,Phases of clinical research ,Cell Biology ,Hematology ,business ,Biochemistry ,Surgery - Abstract
Introduction: The use of high-dose post-transplant cyclophosphamide (PTCY) has revolutionized graft-versus-host disease (GVHD) prophylaxis and allowed to successfully reconsider haplotransplant in recent years. As this strategy significantly reduces the incidence of both acute and chronic GVHD, PTCY has been thereafter considered not only in matched settings but also as sole GVHD prophylaxis, at least when considering myeloablative allotransplant using matched sibling (MSD) or unrelated (MUD) donors and bone marrow as source of graft. Here, PTCY, as a sole GVHD prophylaxis, was tested in a reduced-intensity conditioning (RIC) setting, using peripheral blood stem cells (PBSC) as source of graft considering that this platform is currently broadly used worldwide in adults. Methods: This prospective monocentric phase 2 study was designed with the main objective to demonstrate the feasibility and safety of using only PTCY (without cyclosporine A nor mycophenolate mofetyl after transplant) in adults (18-70 years old) eligible for a RIC PBSC transplant with MSD or MUD. The Baltimore platform with 2 days of PTCY 50mg/kg/day on days 3 and 4 post infusion was considered as conditioning regimen, using fludarabine for lymphoid disease or clofarabine for myeloid disease. The primary objective was to appreciate the incidence of corticosteroid-resistant acute grade 3-4 GVHD (CR 3-4 GVHD) within 100 days post-transplant. According to statistical rules, patients have to be included in a step by step fashion (3, 3, 6, 15, 15 and 17 patients) for a total of 59 evaluable patients (meaning having received PTCY), in order to stop the protocol soon enough in case of excessive rate of deleterious severe acute GVHD (graded according to Mount Sinai International Consortium). Thus, the trial had to be stopped in case of documentation of > 2 CR 3-4 GVHD for the first 3 patients, >3 CR 3-4 GVHD for the first 6 patients, > 4 CR 3-4 GVHD for the first 12 patients, > 6 3-4 CR GVHD for the first 27 patients, > 8 CR 3-4 GVHD for the first 42 patients and finally as soon as > 9 CR 3-4 GVHD for the last included patients. All patients gave informed consent. The trial was registered at ClinicalTrials.gov Identifier: NCT03263767. Results: The results of the first 27 first patients (males n=17 and female n=10; median age: 59 years old (yo), range: 26-70) are reported here. They were included between February 2018 and November 2020. Diagnoses were AML (N=8), MDS (N=5), CMML (N=2), myelofibrosis (N=5), CML (N=1), DLBCL (N=1), T-cell lymphoma (N=1), Philadelphia positive B-ALL (N=1), CLL (N=1), lymphoblastic lymphoma (N=1) and mixed phenotype acute leukemia (N=1). Donors were MSD in 10 cases and MUD in 17. Only one primary graft failure was documented in a 61 yo MDS patient with active disease at transplant. He is however still alive in response after autologous reconstitution. With a median follow-up of 17.6 months (range: 10-42) for alive patients at the time of analysis (July 2021), 1-year and 2-year survivals were 80.9+7% and 74.7+9%, respectively, for both OS et DFS. GVHD-free/relapse-free survival (GRFS) at 1-year and 2-year was 58.7+9% and 52.2+10%, respectively. Three relapses (11%) and 6 deaths occurred. Deaths were due to acute GVHD in 4 patients (including 1 with sepsis and 1 with SARS-COVID 19 infection) and relapse in 2. Grade 2, 3 and 4 acute GVHD occurred in 11, 1 and 4 patients, respectively, for a total of 59% of grade 2-4 acute GVHD. CR 3-4 GVHD was observed in all of 5 patients with acute grade 3-4 GVHD and 4 died related to GVHD. Moderate/severe chronic GVHD occurred in 5/22 (22.7%) evaluable patients, including 4 still on immunosuppressive therapy at 40, 28, 25 and 16 months post-transplant. Overall non-relapse mortality (NRM) was 14.8% and related to acute GVHD. However, the number of cases conducting to stop the protocol was not reached. Conclusion: PTCY as a sole GVHD prophylaxis is here demonstrated as possible and relatively safe for adults receiving a matched PBSC Baltimore-based RIC allograft. The very good survivals reported here may be related to a strong GVL effect associated with the high incidence of acute GVHD. However, because of this high incidence and the fact that NRM was related to GVHD after this first analysis, we have now made an amendment to test the addition to PTCY of one day of anti-thymoglobulin (ATG) 2.5 mg/kg on day-2 for the next 32 patients to be included. This second cohort receiving PTCY+ATG as a sole prophylaxis is ongoing. Disclosures Moreau: Celgene BMS: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Oncopeptides: Honoraria.
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- 2021
38. Peripheral Levels of Monocytic Myeloid-Derived Suppressive Cells at Diagnosis Predict Survivals in AML Patients Eligible for Intensive Chemotherapy
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Sophie Vantyghem, Steven Le Gouill, Catherine Godon, Anne Lok, Pierre Peterlin, Alice Garnier, Thomas Gastinne, Camille Debord, Viviane Dubruille, Soraya Wuilleme, Olivier Theisen, Thierry Guillaume, Philippe Moreau, Yannick Le Bris, Nicolas Blin, Marie C. Béné, Marion Eveillard, Beatrice Mahe, Patrice Chevallier, Amandine Le Bourgeois, Benoit Tessoulin, Maxime Jullien, and Cyrille Touzeau
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Oncology ,medicine.medical_specialty ,Myeloid ,business.industry ,Immunology ,Cell Biology ,Hematology ,Intensive chemotherapy ,Biochemistry ,Peripheral ,medicine.anatomical_structure ,Internal medicine ,medicine ,business - Abstract
Introduction: Myeloid Derived Suppressive Cells (MDSC) constitute a heterogeneous population of immature myeloid cells characterized by their capacity to suppress innate and adaptive immune responses. As such, they have been proven, in solid tumors, to modulate malignancy by increasing tumor cell survival, angiogenesis, metastasis and tissue invasion. By contrast, reports on the role of MDSC in either acute myeloid (AML) or lymphoid (ALL) leukemias are very limited with unknown established impact on long-term outcomes. Patients and Methods: This monocentric prospective study included all adult patients eligible for first-line intensive chemotherapy for AML or ALL. The main objective was to investigate the presence of peripheral blood monocytic MDSC at diagnosis and after induction in such patients and to correlate their levels to complete remission (CR/CR with incomplete platelet recovery), cytologic relapse, leukemia-free (LFS) and overall (OS) survivals. Monocytic MDSCs were defined as CD15- CD34- CD16- CD14+ CD33+ CD11b+ DR-/low cells and assessed in a lysis-no-wash flow cytometry technique. Data acquisition was performed on a Navios® flow cytometer (Beckman Coulter, Miami, FL). MDSC were expressed as a percentage (%) of total nucleated cells defined as CD45+. MDSC% were compared to those of 21 healthy controls. The study was registered at the French Commission Nationale de l'Informatique et des Libertés as CNIL 2016-038. All patients gave informed consent. Analyses were performed in July 2021. Results: Between October 2017 and March 2021, 73 AML and 14 ALL were enrolled (Table 1). The median MDSC% in controls was 0.24% (range: 0.02-1.21). This % was significantly higher in AML compared to ALL (0.19% (range: 0-0.54) vs 0.14% (range: 0-0.35), p=0,01) and differed significantly from controls in ALL (p=0.0004) but not in AML (p=0.94). MDSC% after chemotherapy induction were available for 61 AML and 13 ALL at medians of 37,5 and 37 days, respectively. At that time, median MDSC% were similar between AML (0.84%, range: 0-28) and ALL (0.97%, range: 0-4.75) patients (p=0.52) but significantly higher than in controls for AML patients (p=0.001; ALL p=0.07). AML: MDSC% were not correlated to any other factors, especially ELN2017 classification (p=0.79). ROC curves for LFS established the threshold of 0,55% of MDSC at diagnosis as the best cut-off for analyses. MDSC% (< vs >0,55%) was not predictive of CR/CRp (86.6% n=39/45 vs 78.5% n=22/28, p=0.56). However, 2-year LFS (67.7+8% vs 30.1+10%, p=0.005) and 2-year OS (71.5+8% vs 30.1+10%, p=0.001). (Figure 1) were significantly higher for patients with low MDSC% ( Multivariate analysis confirmed the independent prognostic value of MDCS% at diagnosis for AML patients (LFS p=0.026, HR 3.6, 95%CI 1.88-6.91; OS p=0.02-, HR 2.6, 95%CI 1.11-5.95) together with ELN 2017 classification (LFS p=0.0001, HR 2.34, 95%CI 1.10-4.97; OS p=0.01, HR 2.57, 95%CI 1.18-4.11). ALL: MDSC% at diagnosis were not predictive of response as 13/14 patients achieved CR/CRp after induction. The percentage of MDSC increased significantly between diagnosis (0.14%) and post- induction (0.97%; p=0.002). Again, this had no consequence on relapse incidence in CR/CRp patients nor on LFS and OS when comparing patients based on median post induction MDSC%. Discussion: This study evidenced that a higher percentage of peripheral monocytic MDSC at diagnosis predict lower survivals in AML patients because of more relapse. This result has to be confirmed on larger cohorts as it may implicate to propose immune intervention before or in combination with chemotherapy to improve these patients' outcome. Indeed, these cells seem to be an independent biomarker and potentially promising targets for the development of novel therapeutic strategies. Figure 1 Figure 1. Disclosures Moreau: Sanofi: Honoraria; Amgen: Honoraria; Celgene BMS: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Oncopeptides: Honoraria.
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- 2021
39. Comparable Outcomes Among Adult Patients Allotransplanted for Myelodysplastic Syndrome Using Haploidentical, Matched Unrelated or Matched Sibling Donors: A Single-Center Study
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Thierry Guillaume, Steven Le Gouill, Patrice Chevallier, Benoit Tessoulin, Amandine Le Bourgeois, Marie C. Béné, Maxime Jullien, Beatrice Mahe, Sophie Vantyghem, Thomas Gastinne, Nicolas Blin, Alice Garnier, Cyrille Touzeau, Philippe Moreau, Anne Lok, Pierre Peterlin, and Viviane Dubruille
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Pediatrics ,medicine.medical_specialty ,Adult patients ,business.industry ,Immunology ,Medicine ,Cell Biology ,Hematology ,Sibling ,business ,Single Center ,Biochemistry - Abstract
Introduction: Allogeneic stem cell transplantation (allo-SCT) remains the only curative option for patients with myelodysplastic syndrome (MDS). If recent data have shown encouraging results with haploidentical (haplo) donors in this context, no comparison with allo-SCT using other source of graft (matched sibling [MSD] or unrelated [MUD] donors) has been reported so far. Methods: We retrospectively considered 102 consecutive adults transplanted for MDS between March 2010 and August 2020 in our Department, comparing outcomes between those receiving a graft from a MSD, a MUD or a haplo-donor. Results : Thirty-three, 48 and 21 patients respectively received a graft from a MSD, MUD or haplo donor. Peripheral blood stem cells (PBSC) were the source of graft for all patients. The median age of the whole cohort was 63 years old (range: 20-74) and the median follow-up was 23 months (range: 0-125). The three groups shared similar characteristics (gender, type of MDS, disease status, disease risk index, CMV status, ABO compatibility, peripheral blood stem cells graft count, conditioning regimen) except median recipient age which was younger in matched patients ( 61 vs 65 MUD vs 65 Haplo, p=0,04) and median donor age which was older in matched transplant ( 61 vs 34 MUD vs 42 Haplo, p< 0,001) (Table 1). With a median follow-up of 46,4 months, the 4-year OS (Figure 1) was comparable between the three groups (haplo: 60.1 % ± 11,0 % , MSD: 59,0 % ±9,4 % and MUD: 61.2 % ± 7,2 %, p = 0.88) as well as the 4-year DFS (Figure 2) (55.9 % ± 11,1 % vs 51,2 % ±9,2 % vs 59.6 % ± 7,2 %, p = 0.78) and the cumulative incidence (CI) of NRM (34.6 % ±12,4 % , 15,4% ± 6,4% and 23.8 % ± 6,4 %, p = 0.21). Also, the 4-year CI of acute grade 3-4 GVHD (14,3% vs 15,2% vs 20,8%, p=0.79) and of moderate/severe chronic GVHD (14,3% vs 24.2% vs 27,1%, p=0.56) were not significantly different. The 4-year GRFS seemed better with haplo (Figure 3) but this was not statistically significant (56,1 % ± 11,0% vs 28,1% ±9,2 % vs 32,8 % ± 7,4%,p=0 .41). Conclusions: These data suggest that haplo-identical donors represent a valid alternative in MDS patients lacking a MSD or a MUD for allo-SCT. Figure 1 Figure 1. Disclosures Moreau: Oncopeptides: Honoraria; Amgen: Honoraria; Celgene BMS: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria.
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- 2021
40. Is allogeneic stem cell transplantation for myelofibrosis still indicated at the time of molecular markers and JAK inhibitors era?
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Philippe Moreau, Marie C. Béné, Jacques Delaunay, Maud Voldoire, Olivier Theisen, Nicolas Blin, Mohamad Mohty, Yannick Le Bris, Catherine Godon, Patrice Chevallier, Alice Garnier, Thomas Gastinne, Thierry Guillaume, Beatrice Mahe, Elsa Lestang, Noel Milpied, Viviane Dubruille, Pierre Peterlin, Cyrille Touzeau, and Steven Le Gouill
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Adult ,Male ,Ruxolitinib ,medicine.medical_specialty ,Allogeneic transplantation ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Janus Kinase Inhibitors ,Transplantation, Homologous ,Molecular Targeted Therapy ,Myelofibrosis ,Aged ,Retrospective Studies ,Univariate analysis ,Intention-to-treat analysis ,business.industry ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,General Medicine ,Janus Kinase 2 ,Middle Aged ,Prognosis ,medicine.disease ,Transplantation ,Treatment Outcome ,Primary Myelofibrosis ,030220 oncology & carcinogenesis ,Mutation ,Female ,Stem cell ,business ,Biomarkers ,030215 immunology ,medicine.drug - Abstract
Objective The role of allogenic stem cell transplantation (ASCT) is still debated in myelofibrosis (MF). Methods A retrospective analyzed was performed to compare the outcome of 71 patients with intermediate-2 or high-risk Dynamic International Prognosis Scoring System+ (DIPSS+) primary (PMF) or secondary (SMF) myelofibrosis with an indication of ASCT as they ultimately underwent the procedure (n=34) or not (n=37). Results Five-year overall survival (OS) was not statistically different between both groups (allograft: 52% vs no allograft: 34%, P=.12). However, progression to myelodysplastic syndrome or acute myeloid leukemia at 5 years was significantly lower in transplanted patients (14% vs 50%, P=.01). In univariate analysis, 5-year OS was significantly higher for transplanted vs non-transplanted patients with unfavorable karyotype (75% vs 0%, P=.001), SMF (71% vs 20%, P=.001) or high DIPSS+ score (46% vs 15%, P=.03). There was also a trend for better 5-year OS in allografted patients with high JAK2V617F burden (>65%) (75% vs 8%, P=.07). Interestingly, the survival of patients who did not proceed to ASCT was dramatically increased by the use of ruxolitinib. Conclusions Not all intermediate-2/high-risk DIPSS+ MF patients benefit from ASCT, especially since the introduction of JAK2 inhibitors.
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- 2017
41. Absence of Influence of the Pre-Transplant Immune Status of Recipients on Survivals and Gvhd after Allogeneic Stem Cell Transplantation: A Retrospective Study of 195 Cases
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Marie C. Béné, Patrice Chevalier, Beatrice Mahe, Nicolas Blin, Marion Eveillard, Alice Garnier, Thierry Guillaume, Viviane Dubruille, M. Audrain, Anne Lok, Amandine Le Bourgeois, Benoit Tessoulin, Pierre Peterlin, Sophie Vantyghem, Philippe Moreau, Baptiste Le Calvez, Thomas Dejoie, Cyrille Touzeau, Steven Le Gouill, and Thomas Gastinne
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medicine.medical_specialty ,Myeloid ,Cyclophosphamide ,biology ,business.industry ,Incidence (epidemiology) ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,Biochemistry ,Gastroenterology ,Transplantation ,Regimen ,medicine.anatomical_structure ,Internal medicine ,medicine ,biology.protein ,Stem cell ,Antibody ,business ,medicine.drug - Abstract
Introduction: While many publications have studied immune reconstitution after allogeneic stem cell transplantation (allo-SCT), data exploring whether the pre-transplant immune status (IS) of the recipients has any impact after this procedure are still lacking. Material and Methods: Since May 2017, in our department, the IS of allo-SCT recipients has been systematically investigated at the time of pre-graft check-up. Data of this monocentric retrospective study on post-allo-SCT outcomes are reported here. Information was retrieved from complete blood counts (CBC) in terms of lymphocytes (normal range [NR] 1.5-4x109/L) and monocytes (NR: 0.15-0.9 x109/L). Classical multiparameter flow cytometry and a double platform were used to assess absolute counts of lymphocyte subsets, i.e. CD3+ (NR: 0.9-1.8 x109/L), CD4+ (NR: 0.5-1.2 x109/L), CD8+ (NR: 0.3-0.7 x109/L), CD19+ (NR: 0.1-0.4 x109/L) and CD56+ (NR: 0.1-0.4 x109/L). All patients also benefited from standard serum electrophoresis allowing to appreciate their global level of immunoglobulins (Ig) (NR: 8-13.6 g/L). The impact of pre-graft immune parameters was investigated for overall (OS) and disease-free (DFS) survivals as well as acute and chronic graft-versus-host disease (GVHD) incidence. Results: Between May 2017 and December 2019, 195 consecutive adults were checked for immune status before allo-SCT. They were 117 males and 78 females at a median age of 59 years-old (range: 23-71). The median follow-up for the whole cohort was 21.7 months (range: 5.77-37.5). The majority of patients had a myeloid disease (n=141) and received a reduced intensity (RIC) regimen (n=149, myeloablative [MAC] n=23; sequential n=23). The disease-risk index was low/intermediate and high/very-high for respectively 91 and 104 patients. GVHD prophylaxis included anti-thymocytes globulins (ATG) for 102, post-transplant cyclophosphamide (PTCy) for 54 and both ATG+PTCy for 39. Donors were siblings in 39 cases, matched-unrelated (MUD) in 86, haplo-identical in 66 and 9/10 mis-matched in 4. The IS was evaluated at a median of 20 days (range: 8-72) before allo-SCT. Except for monocytes (median: 0.48 x109/L, range: 0-26), all median immune cell populations were lower than the NR before allo-SCT: lymphocytes (0.84 x109/L, range: 0-8.4), CD3+ (0.7 x109/L, range: 0-3.5), CD4+ (0.37 x109/L, range: 0-2.37), CD8+ (0.25 x109/L, range: 0-2.56), CD19+ (0.005 x109/L, range: 0-0.56), CD56+ (0.097 x109/L, range: 0-0.77). Conversely, the Ig median level was in the NR (8.6 g/L, range: 1.4-28). The percentages of patients with immune cells and Ig above the lowest NR were as follows: lymphocytes: 14.8%, monocytes: 80%, CD3: 37.4%, CD4: 37.4%, CD8: 38.9%, CD19: 16.4%, CD56: 47.6%, Ig: 56.7%. Only 5 patients (2.5%) had a fully normal IS before transplant. Considering the whole cohort, 2-year OS and DFS were 55.6+3% and 50.4+3%, respectively, while incidences of day 100 grade 2-4 and 3-4 acute GVHD and 2-year moderate/severe chronic GVHD were 34.7%, 19.4% and 19.8%, respectively. The comparison of survivals between patients partitioned using either the median of the NR values for immune cells and Ig, showed no difference between subgroups. Similarly, IS had no impact on the incidence of acute nor chronic GVHD. Finally, no difference either was seen according to the conditioning regimen (RIC) or GVHD prophylaxis (ATG, PTCY or both). Conclusion: As expected, almost all pre-ASCT patients present with immune depression. However, pre-transplant IS does not appear to impact survival nor GVHD. This suggests that there is no need to decrease or replace immunosuppressive treatments commonly used in recipients before allo-SCT in the hope to provide better outcomes. Disclosures Touzeau: GlaxoSmithKline: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Sanofi: Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses. Le Gouill:Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria; Loxo Oncology at Lilly: Consultancy. Moreau:Abbvie: Consultancy, Honoraria; Novartis: Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Honoraria.
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- 2020
42. Comparaison des méthodes de modélisation harmonique et application au contrôle de systèmes commutés avec filtrage actif
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Jamal Daafouz, Philippe Feyel, Nicolas Blin, Pierre Riedinger, Louis Grimaud, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and SAFRAN Electronics & Defense
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Dynamic Phasors ,0209 industrial biotechnology ,Harmonic modeling ,Computer science ,020209 energy ,[MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS] ,02 engineering and technology ,Topology ,Extended Harmonic Domain ,[SPI.AUTO]Engineering Sciences [physics]/Automatic ,Domain (software engineering) ,020901 industrial engineering & automation ,0202 electrical engineering, electronic engineering, information engineering ,Decomposition (computer science) ,Linear time-varying systems ,Switched systems ,Harmonic State Space ,Phasor ,[SPI.TRON]Engineering Sciences [physics]/Electronics ,Generalized State-Space Averaging ,Generalized Fourier series ,Harmonics ,Dynamic Harmonic Domain ,Harmonic ,State (computer science) ,Transient (oscillation) - Abstract
International audience; Many harmonic modeling approaches have been introduced in the literature, such as generalized state-space averaging, dynamic phasors, extended harmonic domain, and harmonic state-space. They are capable of capturing both the transient evolution and the steady-state of harmonics. They model the frequency coupling nature of a system and can expose the frequency couplings within interconnected components. By these modeling techniques, a linear time-periodic system can be converted into a linear time-invariant system, which allows the use of traditional analysis and control methods. This paper presents a state of the art of harmonic modeling approaches. Its contribution is to clearly establish the links between the different approaches, in particular through the specification of the decomposition of non-periodic signals in generalized Fourier series with time-varying coefficients. This paper also shows the advantages of harmonic modeling to analyse the frequency couplings within associated systems and to the control with active filtering.; De nombreuses approches pour la modélisation harmonique ont été introduites dans la littérature, telles que la «generalized state-space averaging», les «dynamic phasors», le «extended harmonic domain», et le «harmonic state-space». Elles sont capables de capter à la fois l'évolution transitoire et le régime permanent des harmoniques. Elles modélisent les couplages fréquentiels au sein d'un système et peuvent révéler les couplages fréquentiels entre composants interconnectés. Grâce à ces techniques de modélisation, un système linéaire temps-périodique peut être converti en un système linéaire temps-invariant, ce qui permet l'utilisation des méthodes traditionnelles d'analyse et de contrôle. Cet article présente un état de l'art des techniques de modélisation harmonique. Sa contribution est d'établir clairement les liens entre les différentes approches, notamment par la spécification de la décomposition des signaux non périodiques en séries de Fourier généralisées à coefficients temps-variant. Cet article exploite également les avantages de la modélisation harmonique pour analyser les couplages fréquentiels entre systèmes associés et pour le contrôle avec filtrage actif.
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- 2019
43. FLT3 ligand plasma levels have no impact on outcomes after allotransplant in acute leukemia
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Marion Eveillard, Olivier Theisen, Cyrille Touzeau, Michel Chérel, Nicolas Blin, Joëlle Gaschet, Yannick Le Bris, Anne Lok, Alice Garnier, Antoine Bonnet, Thomas Gastinne, Nelly Robillard, Patrice Chevallier, Marie-C. Béné, Camille Debord, Soraya Wuilleme, Viviane Dubruille, Thierry Guillaume, Steven Le Gouill, Amandine Le Bourgeois, Pierre Peterlin, Beatrice Mahe, Catherine Godon, Philippe Moreau, Bernardo, Elizabeth, Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Département d'hématologie et de biologie [CHU Nantes], Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), This study was supported by a grant from the DHU Oncogreffe of Nantes. https://www.dhu-oncogreffe.com/en, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA)
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0301 basic medicine ,Oncology ,Acute Myeloid Leukemia ,Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Hematopoietic stem cell transplantation ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,FMS-like tyrosine kinase 3 ligand ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Immunology and Allergy ,Humans ,Transplantation, Homologous ,In patient ,Molecular Biology ,Aged ,Acute leukemia ,business.industry ,Myeloid leukemia ,Membrane Proteins ,Hematology ,Plasma levels ,Middle Aged ,Acute Lymphoblastic Leukemia ,3. Good health ,Allogeneic stem cell transplantation ,Haematopoiesis ,Leukemia, Myeloid, Acute ,030104 developmental biology ,surgical procedures, operative ,Treatment Outcome ,Solubility ,030220 oncology & carcinogenesis ,Flt3 ligand ,Female ,business ,Fms-like tyrosine kinase 3 ligand - Abstract
International audience; Objective: This study was designed to assess the impact on outcomes of early soluble Fms-like tyrosine kinase 3 ligand concentrations (sFLc) in patients receiving an allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Methods: This was a prospective monocentric study including all allo-HSCT patients included in the previous FLAM/FLAL study (Peterlin et al., 2019). Blood samples collected before the start of conditioning then post-transplant were frozen, stored and tested by ELISA. The parameters considered were hematopoietic recoveries, Leukemia Free Survival and Overall Survival, acute and chronic GVHD, grade 3 or 4 acute and/or extensive chronic GVHD-free and relapse-free survival (GRFS). Results: Forty-one patients were included, a total of 179 samples were assayed for sFLc. There was no impact of sFLc levels (< =median vs > median) on acute and chronic GVHD incidences, LFS, OS nor GRFS. Conclusion: At variance with induction results for AML (Peterlin et al., 2019) endogenous sFLc do not appear to be a prognostic marker at the time of or after allo-HSCT. Even though the results are negatives, this is, to the best of our knowledge, the only prospective series specifically addressing the question of sFLc impact after allo-HSCT in acute leukemias.
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- 2019
44. Influence of Donor Type (Sibling versus Matched Unrelated Donor versus Haploidentical Donor) on Outcomes after Clofarabine-Based Reduced-Intensity Conditioning Allograft for Myeloid Malignancies
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Beatrice Mahe, Antoine Bonnet, Philippe Moreau, Thomas Gastinne, Viviane Dubruille, Cyrille Touzeau, Nicolas Blin, Thierry Guillaume, Anne Lok, Steven Le Gouill, Louise Bouard, Pierre Peterlin, Yannick Le Bris, Alix Duquenne, Patrice Chevallier, Alice Garnier, Amandine Le Bourgeois, and Marie C. Béné
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Myeloid ,Transplantation Conditioning ,Disease-Free Survival ,Internal medicine ,medicine ,Clofarabine ,Humans ,Sibling ,Aged ,Retrospective Studies ,Transplantation ,business.industry ,Siblings ,Retrospective cohort study ,Hematology ,Matched Unrelated Donor ,Middle Aged ,Survival Rate ,Regimen ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Reduced Intensity Conditioning ,Hematologic Neoplasms ,Cohort ,Transplantation, Haploidentical ,Female ,business ,Unrelated Donors ,medicine.drug ,Follow-Up Studies - Abstract
Clofarabine-based reduced-intensity conditioning (RIC) regimens are well-established schedules for allograft in patients with myeloid malignancies. A retrospective study was conducted including all adults allografted in our department with such a regimen and disease with the aim to assess whether or not the donor type (matched sibling [MSD], matched unrelated [MUD], or haploidentical [haplo]) impacted outcomes. Between October 2009 and February 2018, 118 patients met the inclusion criteria. Thirty-six, 55, and 27 patients received a graft from an MSD, MUD, or haplo donor, respectively. Peripheral blood stem cells (PBSCs) were the source of graft for all patients. The median age of the entire cohort was 62 years (range, 20 to 73), and the median follow-up was 31 months (range, 4.5 to 106). All patients engrafted except 1 haplo recipient. Neutrophils (>.5 × 109/L) and platelets (50 × 109/L) recoveries were significantly delayed in the haplo group (P = .0003 and P
- Published
- 2019
45. Pomalidomide, cyclophosphamide, and dexamethasone for relapsed/refractory multiple myeloma patients in a real-life setting: a single-center retrospective study
- Author
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Anne Lok, Pierre Peterlin, Viviane Dubruille, Thomas Gastinne, Antoine Bonnet, Patrice Chevallier, Steven Le Gouill, Thierry Guillaume, Benoit Tessoulin, Alice Garnier, Cyrille Touzeau, Sabrina Trudel, Nicolas Blin, Beatrice Mahe, Amandine Le Bourgeois, Philippe Moreau, and Maxime Jullien
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Oncology ,Male ,medicine.medical_specialty ,Cyclophosphamide ,Kaplan-Meier Estimate ,Single Center ,Dexamethasone ,03 medical and health sciences ,0302 clinical medicine ,Refractory ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Protease Inhibitors ,Adverse effect ,Lenalidomide ,Multiple myeloma ,Aged ,Retrospective Studies ,Aged, 80 and over ,Salvage Therapy ,business.industry ,Drug Substitution ,Hematology ,General Medicine ,Middle Aged ,Pomalidomide ,medicine.disease ,Hematologic Diseases ,Progression-Free Survival ,Thalidomide ,030220 oncology & carcinogenesis ,Drug Evaluation ,Female ,business ,Multiple Myeloma ,030215 immunology ,medicine.drug - Abstract
Pomalidomide dexamethasone is a standard of care for relapsed multiple myeloma (MM) patients who received at least two prior lines of therapy, including both lenalidomide and proteasome inhibitors (PI). We report here a real-life single-center series of 49 consecutive patients with relapsed and refractory MM treated with the triplet pomalidomide cyclophosphamide dexamethasone (PCD) combination. The median of prior lines of therapy was 3 and all patients were previously exposed to proteasome inhibitors and lenalidomide. The overall response rate was 76%, including 27% very good partial response or better. With a median follow-up of 16 months, the median progression-free survival (PFS) was 7.3 months and the median overall survival was not reached. Regarding safety, most frequent toxicity was hematologic, including 37% grade 3–4 cytopenias. Nine patients (18%) discontinued therapy due to adverse event. Our study confirms that PCD combination is feasible and results in favorable response rate and PFS in comparison with pomalidomide dexamethasone alone.
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- 2019
46. FLT3 ligand plasma levels in acute myeloid leukemia
- Author
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Nelly Robillard, Alice Garnier, Soraya Wuilleme, Marion Eveillard, Olivier Theisen, Patrice Chevallier, Michel Chérel, Yannick Le Bris, Thierry Guillaume, Nicolas Blin, Steven Le Gouill, Camille Debord, Beatrice Mahe, Philippe Moreau, Pierre Peterlin, Amandine Le Bourgeois, Viviane Dubruille, Catherine Godon, Anne Lok, Joëlle Gaschet, Thomas Gastinne, Antoine Bonnet, Marie-Christine Béné, Cyrille Touzeau, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Service d'Hématologie Biologique [CHU Nantes], Unité de Médecine Nucléaire [ICO, Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), This study was supported by a grant from the DHU Oncogreffe of Nantes., Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
- Subjects
Acute Myeloid Leukemia ,Myeloid ,Time Factors ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Kaplan-Meier Estimate ,03 medical and health sciences ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,medicine ,Humans ,Online Only Articles ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Proportional Hazards Models ,0303 health sciences ,business.industry ,Myeloid leukemia ,Disease Management ,Membrane Proteins ,Hematology ,Plasma levels ,Induction Chemotherapy ,medicine.disease ,Prognosis ,cytokines ,Leukemia ,Leukemia, Myeloid, Acute ,Adult Acute Lymphoblastic Leukemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Flt3 ligand ,business ,Biomarkers - Abstract
International audience; no abstract
- Published
- 2019
47. Pleuroparenchymal fibroelastosis after allogeneic hematopoietic stem cell transplantation
- Author
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Nicolas Blin, Martine Reynaud-Gaubert, Julien Gras, Abdellatif Tazi, Anne Huynh, David Michonneau, Franck E. Nicolini, Louise Bondeelle, Stéphane Dominique, Eric Hermet, Gérard Socié, Mauricette Michallet, Anne Bergeron, Véronique Houdouin, Gabriel Thabut, Sylvie Leroy, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), 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), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pneumologie [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), Comparative Genomics Laboratory (CGL), Université du Québec à Montréal = University of Québec in Montréal (UQAM), 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), Institut des Sciences de la Terre de Paris (iSTeP), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), 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 Diderot - Paris 7 (UPD7), Université du Québec à Montréal (UQAM), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), 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 National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]
- Subjects
Transplantation ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,business.industry ,medicine.medical_treatment ,MEDLINE ,Hematopoietic Stem Cell Transplantation ,Hematology ,Hematopoietic stem cell transplantation ,Bioinformatics ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,030228 respiratory system ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,030220 oncology & carcinogenesis ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Medicine ,[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology ,business ,Lung ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2019
48. Multiple myeloma: multicenter and multi-professional development of a reference guide on patient's skills
- Author
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David Feldman, Bernard Delcour, Frédérique Quinio, Maryse Garzia, Cyrille Hulin, Catherine Rioufol, Lucile Maucourant, Nicolas Blin, and Isabelle Madelaine
- Subjects
medicine.medical_specialty ,Health professionals ,business.industry ,education ,Pharmacist ,Hematology ,Disease ,medicine.disease ,Quality of life (healthcare) ,Nursing ,Multi professional ,Physical therapy ,Medicine ,Patient treatment ,business ,Set (psychology) ,Multiple myeloma - Abstract
Introduction: In spite of major advances in treatments, and particularly improvement of patients mean survival, Multiple Myeloma (MM) remains a disease that impacts patients’ quality of life. Thanks to treatment progresses, MM tends to partly resemble to a chronic disease and to become a field of development for patient treatment education (PTE). PTE aims to improve patients’ management by developing their skills as well as those of their immediate circle. The objective of this project is to define the skills of a patient treated for multiple myeloma that could become the purpose for PTE and to gather these skills in a reference guide for health professionals and patients groups. Material and Methods: 7 health professionals (hematologists, pharmacists, treatment education nurses, and psychologists) in 5 different sites with experience in treatment education and/or malignant hemopathies, one patient and one caregiver representing the French Multiple Myeloma Patient Support Group contributed to the writing and the tests of this reference guide. Results: The skills expected from the patients and their close circles as well as the appropriate learning methods were selected. Skills were classified in 3 domains: (1) knowledge: understanding of the disease, the treatments, warning signs, (2) know-how: actions to be taken in case of any problem, (3) behaviors: capacity to explain the disease and the treatments to family members, to know when and who to contact. A set of educational diagnosis tools covering the totality of the 16 priority objectives was developed. These suitable tools were developed to explore these skills; they were tested by health professionals and with patients, and made available. Discussion: We report on the designing process and the development of the content of a reference guide on skills for patients with MM. Each patient is not expected to be acquainted with the whole reference guide. The objective of this project is rather to provide a complete reference guide in order to define the skills to be acquired or to be maintained after an educational diagnosis. A particular attention is drawn to priority objectives, related to patients’ security or presenting a significant impact on quality of life. Ultimately, this reference guide can be used by all individuals managing patients: physician, pharmacist, nurse or psychologist according to the investigated items and also by patient advisors. It is a support for the design, development and evaluation of treatment education programs for fieldwork based on a concept and shared tools in multiple myeloma.
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- 2016
49. Deauville Scores 4 or 5 Assessed by Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Early Post-Allotransplant Is Highly Predictive of Relapse in Lymphoma Patients
- Author
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Franéoise Kraeber-Bodéré, Beatrice Mahe, Steven Le Gouill, Antoine Bonnet, Pierre Peterlin, Caroline Bodet-Milin, Philippe Moreau, Cyrille Touzeau, Amandine Le Bourgeois, Thomas Gastinne, Alice Garnier, Nicolas Blin, Louise Bouard, Thierry Guillaume, Patrice Chevallier, Anne Lok, Viviane Dubruille, Clément Bailly, Marie C. Béné, Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département de Médecine Nucléaire [CHU Nantes], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Nuclear Oncology (CRCINA-ÉQUIPE 13), Département d'hématologie et de biologie [CHU Nantes], Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Département de Médecine Nucléaire [Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, This work was supported in part by grants from the French National Agency for Research ('Investissementsd’Avenir' IRON Labex no. ANR-11-LABX-0018-01 and ArronaxPlusEquipex no. ANR-11-EQPX-0004)., ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Bernardo, Elizabeth, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, and Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Lymphoma ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Fluorodeoxyglucose F18 ,Predictive Value of Tests ,Recurrence ,Internal medicine ,Positron Emission Tomography Computed Tomography ,medicine ,T-cell lymphoma ,Humans ,Transplantation, Homologous ,Adult Hodgkin Lymphoma ,Aged ,Retrospective Studies ,Transplantation ,Hematology ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,(18)F-FDG-PET CT ,Middle Aged ,medicine.disease ,Survival Analysis ,3. Good health ,Allogeneic stem cell transplantation ,Deauville scale ,030220 oncology & carcinogenesis ,Cohort ,Female ,Radiology ,business ,030215 immunology - Abstract
International audience; The impact of early fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) status on survival after allogeneic transplantation for lymphoma is poorly reported. This retrospective study included all adult Hodgkin lymphoma (HL) or non-Hodgkin lymphoma(NHL) patients (>18 years old) who benefited from FDG PET-CT before (within 1 month) and/or early (+3 months and within +6 to 9 months) after allogeneic stem cell transplantation in our institution between 2005 and 2015 and who were still without documented progression or relapse at the time of the FDG PET-CT. All FDG PET-CT were reviewed by a nuclear medicine expert in hematology and restaged according to the Deauville scale. FDG-PET CT was considered positive when the uptake was higher than liver background (Deauville score 4). The primary objective was to study the impact of pre-and post-transplant FDG PET-CT on lymphoma-free survival (LFS) and overall survival (OS). Inclusion criteria were fulfilled for 103 patients (69 men; median age, 51.6 years old; range, 22 to 67). Diagnoses were high-grade NHL (n = 47), low-grade NHL (n = 6), T cell lymphoma (n = 34), and HL (n = 16). More than half of the patients were in complete remission at the time of transplant (n = 56). A reduced-intensity conditioning regimen was applied in most cases (n = 90). With a median follow-up of 49.5 months (range, 6 to 140.5) for alive patients, median 3-year OS and LFS were, respectively, 81% (range, 71% to 87%) and 65% (range, 54% to 74%) for the entire cohort. In multivariate analysis, positive FDG PET-CT at 3 months was the strongest independent factor significantly associated with poorer LFS (hazard ratio, 9.22; 95% confidence interval, 1.88 to 645.2; P = .006). FDG PET-CT positivity at 3 months appears to be highly predictive of LFS in patients after allogeneic transplantation and may help to guide strategies to prevent relapse. These results need to be validated prospectively.
- Published
- 2018
50. Resilience to cognitive aging is associated with responsiveness of dentate neurons generated throughout adult life
- Author
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Nicolas Blin, M.F. Montaron, Djoher Nora Abrous, Vanessa Charrier, and Pierre Garcia
- Subjects
Cognitive aging ,Adult life ,Successful aging ,Neurogenesis ,Cognition ,Biology ,Hippocampal formation ,Learning abilities ,Neuroscience ,Immediate early gene - Abstract
During aging some individuals are resilient to the decline of cognitive functions whereas others are vulnerable. These inter-individual differences in memory abilities have been associated with differences in the rate of hippocampal neurogenesis measured at old age. Whether the maintenance of the functionality of neurons generated throughout adult life is linked to resilience to cognitive aging remains completely unexplored. Using the immediate early gene Zif268, we analysed the activation of dentate granule neurons born in adult (3 month-old), middle-aged (12 month-old) or senescent (18 month-old) rats (n=96) in response to learning when animals reached 21 month-old. The activation of neurons born during the developmental period was also examined. We show that neurons generated 4, 10 or 19 months before learning (and not developmentally born neurons) are activated in senescent rats with good learning abilities. In contrast, aged rats with bad learning abilities do not exhibit an activity-dependent regulation of Zif268. In conclusion, we propose that resilience to cognitive aging is associated to the responsiveness of neurons born during adult-life. These data add to our current knowledge by showing that the aging of memory abilities stems not only from the number but also from the responsiveness of adult-born neurons. Keywords: Successful aging, Adult neurogenesis, Hippocampus, Spatial memory, Plasticity, Resilience.
- Published
- 2018
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