Author: "Feugier, A." / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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1. Evolutionary history of transformation from chronic lymphocytic leukemia to Richter syndrome

Author: Parry, Erin M, Leshchiner, Ignaty, Guièze, Romain, Johnson, Connor, Tausch, Eugen, Parikh, Sameer A, Lemvigh, Camilla, Broséus, Julien, Hergalant, Sébastien, Messer, Conor, Utro, Filippo, Levovitz, Chaya, Rhrissorrakrai, Kahn, Li, Liang, Rosebrock, Daniel, Yin, Shanye, Deng, Stephanie, Slowik, Kara, Jacobs, Raquel, Huang, Teddy, Li, Shuqiang, Fell, Geoff, Redd, Robert, Lin, Ziao, Knisbacher, Binyamin A, Livitz, Dimitri, Schneider, Christof, Ruthen, Neil, Elagina, Liudmila, Taylor-Weiner, Amaro, Persaud, Bria, Martinez, Aina, Fernandes, Stacey M, Purroy, Noelia, Anandappa, Annabelle J, Ma, Jialin, Hess, Julian, Rassenti, Laura Z, Kipps, Thomas J, Jain, Nitin, Wierda, William, Cymbalista, Florence, Feugier, Pierre, Kay, Neil E, Livak, Kenneth J, Danysh, Brian P, Stewart, Chip, Neuberg, Donna, Davids, Matthew S, Brown, Jennifer R, Parida, Laxmi, Stilgenbauer, Stephan, Getz, Gad, and Wu, Catherine J
Subjects: Cancer, Rare Diseases, Lymphoma, Genetics, Hematology, Human Genome, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Serine-Arginine Splicing Factors, Medical and Health Sciences, Immunology
Abstract: Richter syndrome (RS) arising from chronic lymphocytic leukemia (CLL) exemplifies an aggressive malignancy that develops from an indolent neoplasm. To decipher the genetics underlying this transformation, we computationally deconvoluted admixtures of CLL and RS cells from 52 patients with RS, evaluating paired CLL-RS whole-exome sequencing data. We discovered RS-specific somatic driver mutations (including IRF2BP2, SRSF1, B2M, DNMT3A and CCND3), recurrent copy-number alterations beyond del(9p21)(CDKN2A/B), whole-genome duplication and chromothripsis, which were confirmed in 45 independent RS cases and in an external set of RS whole genomes. Through unsupervised clustering, clonally related RS was largely distinct from diffuse large B cell lymphoma. We distinguished pathways that were dysregulated in RS versus CLL, and detected clonal evolution of transformation at single-cell resolution, identifying intermediate cell states. Our study defines distinct molecular subtypes of RS and highlights cell-free DNA analysis as a potential tool for early diagnosis and monitoring.
Published: 2023

2. Brentuximab Vedotin Plus AVD for First-Line Treatment of Early-Stage Unfavorable Hodgkin Lymphoma (BREACH)

Author: Fornecker, Luc-Matthieu, Lazarovici, Julien, Aurer, Igor, Casasnovas, René-Olivier, Gac, Anne-Claire, Bonnet, Christophe, Bouabdallah, Krimo, Feugier, Pierre, Specht, Lena, Molina, Lysiane, Touati, Mohamed, Borel, Cécile, Stamatoullas, Aspasia, Nicolas-Virelizier, Emmanuelle, Pascal, Laurent, Lugtenburg, Pieternella, Di Renzo, Nicola, Vander Borght, Thierry, Traverse-Glehen, Alexandra, Dartigues, Peggy, Hutchings, Martin, Versari, Annibale, Meignan, Michel, Federico, Massimo, André, Marc, LYSA-FIL-EORTC Intergroup, Hematology, UCL - (MGD) Service d'hématologie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne
Subjects: Adult, Brentuximab Vedotin, Cancer Research, Adolescent, Middle Aged, Vinblastine, Hodgkin Disease, Dacarbazine, Hodgkin lymphoma, brentuximab vedotin, Young Adult, Bleomycin, Treatment Outcome, Oncology, SDG 3 - Good Health and Well-being, Doxorubicin, Antineoplastic Combined Chemotherapy Protocols, Humans, Neoplasm Staging
Abstract: PURPOSE The prognosis of patients with early-stage unfavorable Hodgkin lymphoma remains unsatisfactory. We assessed the efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV-AVD) in previously untreated, early-stage unfavorable Hodgkin lymphoma (ClinicalTrials.gov identifier: NCT02292979 ). METHODS BREACH is a multicenter, randomized, open-label, phase II trial. Eligible patients were age 18-60 years with ≥ 1 unfavorable EORTC/LYSA criterion. Patients were randomly assigned (2:1) to four cycles of BV-AVD or standard doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD), followed by 30 Gy involved node radiotherapy. The primary end point was the positron emission tomography (PET) response rate after two cycles by expert independent review using the Deauville score. The study was designed to test if the PET-negative rate after two cycles of BV-AVD was superior to 75%. We hypothesized a 10% increase in the PET-negative rate after two cycles of BV-AVD. RESULTS Between March 2015 and October 2016, 170 patients were enrolled. After two cycles, the primary end point of the study was met: 93 (82.3%; 90% CI, 75.3 to 88.0) of 113 patients in the BV-AVD arm were PET-negative (Deauville score 1-3) compared with 43 (75.4%; 90% CI, 64.3% to 84.5%) of 57 in the ABVD arm. The 2-year progression-free survival (PFS) was 97.3% (95% CI, 91.9 to 99.1) and 92.6% (95% CI, 81.4% to 97.2%) in the BV-AVD and ABVD arms, respectively. High total metabolic tumor volume was associated with a significantly shorter PFS (hazard ratio, 17.9; 95% CI, 2.2 to 145.5; P < .001). For patients with high total metabolic tumor volume, the 2-year PFS rate was 90.9% (95% CI, 74.4 to 97.0) and 70.7% (95% CI, 39.4% to 87.9%) in the BV-AVD and ABVD arms, respectively. CONCLUSION BV-AVD demonstrated an improvement in the PET-negative rate compared with ABVD after two cycles.
Published: 2023

3. Positron Emission Tomography–Driven Strategy in Advanced Hodgkin Lymphoma: Prolonged Follow-Up of the AHL2011 Phase III Lymphoma Study Association Study

Author: René-Olivier Casasnovas, Reda Bouabdallah, Pauline Brice, Julien Lazarovici, Hervé Ghesquieres, Aspasia Stamatoullas, Jehan Dupuis, Anne-Claire Gac, Thomas Gastinne, Bertrand Joly, Krimo Bouabdallah, Emmanuelle Nicolas-Virelizier, Pierre Feugier, Franck Morschhauser, David Sibon, Christophe Bonnet, Alina Berriolo-Riedinger, Véronique Edeline, Marie Parrens, Diane Damotte, Diane Coso, Marc André, Michel Meignan, Cédric Rossi, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'hématologie
Subjects: Adult, Cancer Research, Adolescent, Neoplasms, Second Primary, Middle Aged, Vinblastine, Hodgkin Disease, Dacarbazine, Bleomycin, Young Adult, Oncology, Doxorubicin, Vincristine, Positron-Emission Tomography, Procarbazine, Antineoplastic Combined Chemotherapy Protocols, Humans, Prednisone, Cyclophosphamide, Etoposide, Follow-Up Studies, Neoplasm Staging
Abstract: PURPOSE The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747 ) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results. METHODS Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2– and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment. RESULTS In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% v 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; P = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; P = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2–/PET4–, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4– and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; P < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4– patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; P = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; P = .038) had a significant lower OS than PET2–/PET4– patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively. CONCLUSION The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.
Published: 2022
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4. Economic burden in non‐Hodgkin lymphoma survivors: The French Lymphoma Study Association SIMONAL cross‐sectional study

Author: Nicolas Mounier, Christophe Guyeux, Macha Woronoff-Lemsi, David Sibon, Loic Ysebaert, Michel Henry-Amar, Virginie Nerich, Gandhi Damaj, Jean-Philippe Jais, Vincent Ribrag, Franck Morschhauser, Corinne Haioun, Pierre Feugier, Hervé Tilly, Florence Broussais-Guillaumot, Gilles Salles, Catherine Thieblemont, René-Olivier Casasnovas, Emmanuelle Nicolas-Virelizier, and Raphaël Couturier
Subjects: Cancer Research, medicine.medical_specialty, Lymphoma, Cross-sectional study, Financial Stress, Transplantation, Autologous, Autologous stem-cell transplantation, Health care, medicine, Humans, Survivors, Retrospective Studies, business.industry, Lymphoma, Non-Hodgkin, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, Health Care Costs, medicine.disease, Cross-Sectional Studies, Oncology, Cost driver, Family medicine, Health care cost, Rituximab, business, medicine.drug
Abstract: BACKGROUND No study has focused on the economic burden in non-Hodgkin lymphoma (NHL) survivors, even though this knowledge is essential. This study reports on health care resource use and associated health care costs as well as related factors in a series of 1671 French long-term NHL survivors. METHODS Health care costs were measured from the payer perspective. Only direct medical costs (medical consultations, outpatient treatments, hospitalizations, and medical transport) in the past 12 months were included (reference year 2015). Multiple linear regression was used to search for explanatory factors of health care costs. RESULTS In total, 1100 survivors (66%) reported having used at least 1 health care resource, and 867 (52%) reported having used at least 1 outpatient treatment. After the authors accounted for missing data, the mean health care cost was estimated at €702 ± €2221. Hospitalizations and outpatient treatments were the main cost drivers. Sensitivity analyses confirmed the robustness of the results. For the 1100 survivors who reported using at least 1 health care resource, the mean health care cost was €1067 ± €2268. Several factors demonstrated statistically significant relationships with health care costs. For instance, cardiovascular disorders increased costs by 66% ± 16%. In contrast, rituximab or autologous stem cell transplantation as initial therapy had no effect on health care costs. CONCLUSIONS The consideration of economic constraints in health care is now a reality. This retrospective study reports on a better understanding of health care resource use and associated health care costs as well as related factors. It may help health care professionals in their ongoing efforts to design person-centered health care pathways.
Published: 2021
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5. Six-Year Results From RELEVANCE: Lenalidomide Plus Rituximab (R

Author: Franck, Morschhauser, Loretta, Nastoupil, Pierre, Feugier, Jean-Marc, Schiano de Colella, Hervé, Tilly, Maria Lia, Palomba, Emmanuel, Bachy, Christophe, Fruchart, Edward N, Libby, Rene-Olivier, Casasnovas, Ian W, Flinn, Corinne, Haioun, Hervé, Maisonneuve, Loic, Ysebaert, Nancy L, Bartlett, Kamal, Bouabdallah, Pauline, Brice, Vincent, Ribrag, Steven, Le Gouill, Nicolas, Daguindau, Stéphanie, Guidez, Gian Matteo, Pica, Alejandro Martín, García-Sancho, Armondo, López-Guillermo, Jean-François, Larouche, Kiyoshi, Ando, Maria, Gomes da Silva, Marc, André, Wu, Kalung, Laurie H, Sehn, Koji, Izutsu, Guillaume, Cartron, Argyrios, Gkasiamis, Russell, Crowe, Luc, Xerri, Nathan H, Fowler, and Gilles, Salles
Subjects: Survival Rate, Antineoplastic Combined Chemotherapy Protocols, Humans, Neoplasms, Second Primary, Rituximab, Lenalidomide, Lymphoma, Follicular
Published: 2022

6. Prolonged in‐hospital stay and higher mortality after Covid‐19 among patients with <scp>non‐Hodgkin</scp> lymphoma treated with B‐cell depleting immunotherapy

Author: Roberta Di Blasi, Laure Philippe, Thomas Hueso, Catherine Thieblemont, Karine Lacombe, Bénédicte Deau Fischer, Serge Bologna, Caroline Besson, Guillemette Fouquet, Sylvain Choquet, Milena Kohn, Rémy Duléry, Carole Soussain, Bernard Drenou, Pierre Feugier, Etienne Daguindau, Marc Delord, Nicolas Noel, Adrien Chauchet, Sylvain Lamure, Sandra Malak, Cédric Rossi, Bertrand Joly, Guillaume Cartron, Yassine Taoufik, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier de Versailles André Mignot (CHV), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Gustave Roussy (IGR), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Saint-Cloud], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Oncologie de Gentilly, Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Service d'Hématologie [CH Annecy], CH Annecy, Hôpital Bicêtre, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Roche, Takeda Pharmaceutical Company, TPC, We thank all the clinicians and patients in the participating centers for their contributions to this multicenter study. We are grateful to the Centre Hospitalier de Versailles, in particular Philippe Rousselot and Laure Morisset for promoting the research and for supporting the editing. We thank France Lymphome Espoir for reviewing the study material, LYSA for discussions on the design of this study, and Sophie Rigaudeau and C?cile Laur?ana for their contribution to the collection of the cases., Rémy Duléry reports personal fees from Takeda, Novartis, and Biotest and non‐financial support from Gilead outside the submitted work. Roberta Di Blasi reports personal fees from Gilead and Novartis outside the submitted work. Serge Bologna reports personal fees from Janssen and Roche outside the submitted work. Guillaume Cartron reports personal fees from Roche, Celgene, Sanofi, Gilead, Janssen, and Abbvie outside the submitted work. Karine Lacombe reports personal fees and non‐financial support from Gilead, MSD, Abbvie, ViiV Healthcare, and Janssen outside the submitted work. Caroline Besson reports research funding from Roche and non‐financial support from Takeda and Roche outside the submitted work., HAL UVSQ, Équipe, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Groupe hospitalier de la région de Mulhouse et Sud-Alsace, Département d'Oncologie Médicale [Centre René-Huguenin, Saint-Cloud], Hôpital René HUGUENIN (Saint-Cloud), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, [SDV]Life Sciences [q-bio], MESH: COVID-19 / complications, Comorbidity, MESH: Lymphoma, Non-Hodgkin / complications, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, MESH: Age Factors, Young adult, Research Articles, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Aged, 80 and over, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, B-Lymphocytes, education.field_of_study, Lymphoma, Non-Hodgkin, MESH: SARS-CoV-2, Hazard ratio, Age Factors, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Combined Modality Therapy, MESH: Antigens, CD20 / immunology, 3. Good health, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Rituximab, B-cell depleting immunotherapy, Immunotherapy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Research Article, medicine.drug, Adult, medicine.medical_specialty, Population, lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, anti-CD20 therapy, Young Adult, MESH: Rituximab / administration & dosage, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: COVID-19 / mortality, Internal medicine, medicine, Humans, education, MESH: B-Lymphocytes / drug effects, Survival analysis, Aged, Proportional Hazards Models, Retrospective Studies, MESH: Aged, 80 and over, SARS-CoV-2, Proportional hazards model, business.industry, COVID-19, Retrospective cohort study, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, MESH: Combined Modality Therapy, Length of Stay, vaccination, Antigens, CD20, medicine.disease, Survival Analysis, Lymphoma, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Drug Resistance, Neoplasm, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030215 immunology
Abstract: International audience; Prolonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow-up of 191 days (3–260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.
Published: 2021
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7. Obinutuzumab vs rituximab for advanced DLBCL: a PET-guided and randomized phase 3 study by LYSA

Author: Gandhi Damaj, Steven Le Gouill, Christophe Bonnet, Hervé Ghesquières, David Sibon, Marc André, Emmanuel Itti, Loïc Chartier, Françoise Kraeber-Bodéré, Luc Fornecker, Hervé Tilly, Vincent Ribrag, Franck Morschhauser, Jean-Philippe Jais, Caroline Bodet-Milin, Alina Berriolo-Riedinger, Krimo Bouhabdallah, Philippe Ruminy, Guillaume Cartron, Catherine Thieblemont, Remy Gressin, Reda Bouhabdallah, Corinne Haioun, Lucie Oberic, Thierry Jo Molina, René-Olivier Casasnovas, Pierre Feugier, Josette Brière, Thierry Lamy, and Hervé Maisonneuve
Subjects: medicine.medical_specialty, Immunology, CHOP, Antibodies, Monoclonal, Humanized, Biochemistry, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, International Prognostic Index, Obinutuzumab, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Cyclophosphamide, business.industry, Cell Biology, Hematology, medicine.disease, Chemotherapy regimen, 3. Good health, Transplantation, chemistry, Doxorubicin, Vincristine, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Prednisone, Vindesine, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, 030215 immunology, medicine.drug
Abstract: Rituximab plus polychemotherapy is the standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED, a randomized phase 3 trial, compared obinutuzumab to rituximab. Transplant-eligible patients (18-60 years) with an untreated age-adjusted International Prognostic Index (aaIPI) score ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab and stratified by aaIPI (1; 2-3) and chemotherapy regimen (doxorubicin, cyclophosphamide, prednisone plus vindesine, bleomycin [ACVBP] or vincristine [CHOP]). Consolidation treatment was determined according to response to interim positron emission tomography (PET). Responders after cycle 2 and 4 (PET2−/PET4−) received immunochemotherapy. Responders after only cycle 4 (PET2+/4−) received transplantation. The primary objective was an 8% improvement (hazard ratio [HR] = 0.73; 80% power; α risk, 2.5%; 1-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. From September 2012, 670 patients were enrolled (obinutuzumab, n = 336; rituximab, n = 334). A total of 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP. Median follow-up was 38.7 months. The 2-year EFS was similar in both groups (59.8% vs 56.6%; P = .123; HR = 0.88). The 2-year PFS in the whole cohort was 83.1% (95% confidence interval, 80% to 85.8%). PET2−/4− and PET2+/4− had similar 2-year progression-free survival (PFS) and overall survival (OS): 89.9% vs 83.9% and 94.8% vs 92.8%. The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in aaIPI ≥1 DLBCL transplant-eligible patients. This trial was registered at www.clinicaltrials.gov as #NCT01659099.
Published: 2021
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8. High-risk stage IIB Hodgkin lymphoma treated in the H10 and AHL2011 trials: total metabolic tumor volume is a useful risk factor to stratify patients at baseline

Author: Cédric Rossi, Marc André, Jehan Dupuis, Franck Morschhauser, Bertrand Joly, Julien Lazarovici, Hervé Ghesquières, Aspasia Stamatoullas, Emmanuelle Nicolas-Virelizier, Pierre Feugier, Anne-Claire Gac, Hannah Moatti, Luc-Matthieu Fornecker, Bénédicte Deau, Clémentine Joubert, Catherine Fortpied, John Raemaekers, Massimo Federico, Salim Kanoun, Michel Meignan, Alexandra Traverse-Glehen, Anne-Ségolène Cottereau, and René-Olivier Casasnova
Subjects: Dacarbazine, Bleomycin, Clinical Trials, Phase III as Topic, Doxorubicin, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, Humans, Hematology, Prognosis, Vinblastine, Hodgkin Disease, Tumor Burden, Randomized Controlled Trials as Topic
Abstract: Stage IIB Hodgkin lymphoma (HL) patients, with a mediastinum-to-thorax (M/T) ratio of ≥0.33 or extranodal localization have a poor prognosis and are treated either as limited or advanced stage. We compared these two approaches in patients included in two randomized phase III trials enrolling previously untreated early (H10) or advanced stage HL (AHL2011). We included HL patients with Ann-Arbor stage IIB with M/T ≥0.33 or extranodal involvement enrolled in the H10 or AHL2011 trials with available positron emission tomography at baseline (PET0) and after two cycles of chemotherapy (PET2). Baseline total metabolic tumor volume (TMTV) was calculated using the 41% SUVmax method. PET2 response assessment used the Deauville score. One hundred and fourty-eight patients were eligible, including 83 enrolled in the AHL2011 trial and 65 in the H10 trial. The median TMTV value was 155.5 mL (range, 8.3-782.9 mL), 165.6 mL in AHL2011 and 147 mL in H10. PET2 positivity rates were 16.9% (n=14) and 9.2% (n=6) in AHL2011 and H10 patients, respectively. With a median follow-up of 4.1 years (95% confidence interval [CI]: 3.9-4.4), overall 4-year PFS was 88.0%, 87.0% in AHL2011 and 89.2% in H10. In univariate and mutivariate analyses, baseline TMTV and PET2 response influenced significantly progression-free survival (hazard ratio [HR]=4.94, HR=3.49 respectively). Notably, among the 16 patients who relapsed, 13 (81%) had a baseline TMTV baseline ≥155 mL. Upfront ABVD plus radiation therapy or upfront escBEACOPP without radiotherapy provide similar patient’s outcome in high-risk stage IIB HL. TMTV is useful to stratify these patients at baseline.
Published: 2022

9. Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma

Author: Maud D'Aveni-Piney, Catherine Thieblemont, Caroline Bodet-Milin, Loic Ysebaert, Pierre Feugier, Eugenio Galli, Marie-Thérèse Rubio, Roberta Di Blasi, Pierre Bories, Benoit Tessoulin, Pierre Olivier, Ingrid Lafon, Alina Berriolo-Riedinger, Sylvie Chevret, Sophie Bernard, Laetitia Vercellino, Céline Bossard, Salim Kanoun, Lucie Oberic, Pascal Merlet, Michel Meignan, Olivier Casasnovas, Steven Le Gouill, Véronique Meignin, Cédric Rossi, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Nucléaire [Toulouse], CHU Toulouse [Toulouse], 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), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Service de Médecine Nucléaire [Nancy], Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] (CGFL), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Henri Mondor, Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), NF-kappaB, Différenciation et Cancer (OncokappaB (URP_7324)), and Université de Paris (UP)
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Immunotherapy, Adoptive, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, Refractory, Internal medicine, medicine, Humans, Progression-free survival, Stage (cooking), Retrospective Studies, Univariate analysis, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Progression-Free Survival, Confidence interval, Tumor Burden, 3. Good health, Lymphoma, 030104 developmental biology, 030220 oncology & carcinogenesis, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma
Abstract: Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).
Published: 2020
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10. Arterial endofibrosis in endurance athletes: Prospective comparison of the diagnostic accuracy of intra-arterial digital subtraction angiography and computed tomography angiography

Author: Olivier Rouvière, L. Perrier, Muriel Rabilloud, R. Boutier, M. Bedel, C. Goutain-Majorel, M. Papillard, N. Girouin, P. Feugier, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Computed Tomography Angiography, [SDV]Life Sciences [q-bio], Concordance, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, McNemar's test, Interquartile range, medicine, Deep Femoral Artery, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Circumflex, Computed tomography angiography, Radiological and Ultrasound Technology, medicine.diagnostic_test, business.industry, Angiography, Digital Subtraction, General Medicine, Digital subtraction angiography, Confidence interval, Athletes, 030220 oncology & carcinogenesis, Female, Tomography, X-Ray Computed, Nuclear medicine, business
Abstract: Purpose To prospectively compare the diagnostic capabilities of computed tomography angiography (CTA) to those of digital subtraction angiography (DSA) in endurance athletes with suspicion of arterial endofibrosis. Materials and methods Forty-five athletes (39 men, 6 women; median age: 30 years, interquartile range: 23–42 years) prospectively underwent DSA and CTA without (n = 5) or with (n = 40) electrocardiogram gating. DSA was interpreted by a single expert (experience of 15 years). CTA was independently interpreted by three other readers (experience of 5–8 years). Readers assessed the presence and degree of stenoses on iliac and femoral arteries and the overall diagnosis (negative, uncertain, positive) of endofibrosis at the limb level. Sensitivities and specificities of DSA and CTA were estimated at the limb level using histological findings and long-term follow-up as reference, and compared using the McNemar test. Results For diagnosing and quantifying stenoses, concordance between DSA and CTA was moderate-to-good for common and external iliac arteries, moderate for lateral circumflex arteries and poor-to-moderate for the other branches of the deep femoral artery. It was good for all readers for the overall diagnosis of endofibrosis. After long-term follow-up (median, 95 months; interquartile range: 7–109 months), DSA sensitivity and specificity were respectively 88.6% (39/44; 95% confidence interval [CI]: 76–95%) and 75% (24/32; 95% CI: 57.9–86.7%); CTA sensitivity and specificity were respectively 88.6% (39/44; 95% CI: 76–95%; P > 0.99) and 84.4% (27/32; 95% CI: 68.2–93.1%; P = 0.51), 86.3% (38/44; 95% CI: 73.3–93.6%; P > 0.99) and 75% (24/32; 95% CI: 57.9–86.7%; P > 0.99), and 84.1% (37/44; 95% CI: 70.6–92.1%; P = 0.68) and 75% (24/32; 95% CI: 57.9–86.7%; P > 0.99) for the three readers. Conclusion CTA shows performances similar to those of DSA in predicting the long-term diagnosis of endofibrosis in endurance athletes with suggestive symptoms.
Published: 2020
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11. High total metabolic tumor volume at baseline predicts survival independent of response to therapy

Author: Julie Abraham, Marc Simon, Hervé Tilly, Josette Brière, Anne-Ségolène Cottereau, Lucie Oberic, Michel Meignan, Olivier Casasnovas, Olivier Fitoussi, Pascal Godmer, Christophe Fruchart, Laurence Sanhes, Laetitia Vercellino, Gian Matteo Pica, Pierre Feugier, Gilles Salles, Vincent Ribrag, Catherine Thieblemont, Armando López-Guillermo, Judith Trotman, Bernadette Corront, Loïc Chartier, Hugo Gonzalez, Franck Morschhauser, Philippe Gaulard, Bachra Choufi, Catherine Sebban, L. Roulin, Reda Bouabdallah, and Sylvia Snauwaert
Subjects: Male, Oncology, Vincristine, medicine.medical_specialty, Immunology, Population, Angiogenesis Inhibitors, Standardized uptake value, Biochemistry, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, Prednisone, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Stage (cooking), education, Cyclophosphamide, Lenalidomide, neoplasms, Aged, Aged, 80 and over, education.field_of_study, business.industry, Cell Biology, Hematology, Middle Aged, Prognosis, Tumor Burden, Doxorubicin, 030220 oncology & carcinogenesis, Female, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, medicine.drug
Abstract: Early identification of ultra-risk diffuse large B-cell lymphoma (DLBCL) patients is needed to aid stratification to innovative treatment. Previous studies suggested high baseline total metabolic tumor volume (TMTV) negatively impacts survival of DLBCL patients. We analyzed the prognostic impact of TMTV and prognostic indices in DLBCL patients, aged 60 to 80 years, from the phase 3 REMARC study that randomized responding patients to R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) into maintenance lenalidomide or placebo. TMTV was computed on baseline positron emission tomography/computed tomography using the 41% maximum standardized uptake value method; the optimal TMTV cutoff for progression-free (PFS) and overall survival (OS) was determined and confirmed by a training validation method. There were 301 out of 650 evaluable patients, including 192 patients classified as germinal center B-cell–like (GCB)/non-GCB and MYC/BCL2 expressor. Median baseline TMTV was 238 cm3; optimal TMTV cutoff was 220 cm3. Patients with high vs low TMTV showed worse/higher Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, stage III or IV disease, >1 extranodal site, elevated lactate dehydrogenase, International Prognostic Index (IPI) 3-5, and age-adjusted IPI 2-3. High vs low TMTV significantly impacted PFS and OS, independent of maintenance treatment. Although the GCB/non-GCB profile and MYC expression did not correlate with TMTV/survival, BCL2 >70% impacted PFS and could be stratified by TMTV. Multivariate analysis identified baseline TMTV and ECOG PS as independently associated with PFS and OS. Even in responding patients, after R-CHOP, high baseline TMTV was a strong prognosticator of inferior PFS and OS. Moreover, TMTV combined with ECOG PS may identify an ultra-risk DLBCL population. This trial was registered at www.clinicaltrials.gov as #NCT01122472.
Published: 2020
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12. Treatment of Older Patients With Mantle Cell Lymphoma (MCL)

Author: Hervé Tilly, Gilles Salles, Wolfram Klapper, Stephan Stilgenbauer, Martin Dreyling, Christian Schmidt, Michael Unterhalt, Pierre Feugier, Eva Hoster, Christiane Pott, Josée M. Zijlstra, Lothar Kanz, Jan Walewski, Vincent Ribrag, Michal Szymczyk, Jeanette K. Doorduijn, Olivier Hermine, Marek Trneny, Christian H. Geisler, Florian Kaiser, Hanneke C. Kluin-Nelemans, Catherine Thieblemont, Stem Cell Aging Leukemia and Lymphoma (SALL), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Hematology, and CCA - Cancer Treatment and quality of life
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Long term follow up, Follicular lymphoma, Lymphoma, Mantle-Cell, Maintenance Chemotherapy, Time, BENDAMUSTINE PLUS RITUXIMAB, Text mining, MULTICENTER PHASE-II, Older patients, immune system diseases, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Progression-free survival, Cyclophosphamide, Aged, PROGNOSTIC INDEX, Aged, 80 and over, TRANSPLANTATION, business.industry, Induction Chemotherapy, Middle Aged, INDOLENT, medicine.disease, Transplantation, 1ST-LINE TREATMENT, MAINTENANCE, Doxorubicin, Vincristine, Prednisone, Female, Mantle cell lymphoma, B-R, Rituximab, business, FOLLICULAR LYMPHOMA, Vidarabine, Follow-Up Studies, PROGRESSION-FREE SURVIVAL
Abstract: PURPOSE In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209 ), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years ( P < .001) and 7.1 years ( P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe.
Published: 2020
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13. Increasing the diversity of dietary fibers in a daily-consumed bread modifies gut microbiota and metabolic profile in subjects at cardiometabolic risk

Author: Harimalala Ranaivo, Florence Thirion, Christel Béra-Maillet, Susie Guilly, Chantal Simon, Monique Sothier, Laurie Van Den Berghe, Nathalie Feugier-Favier, Stéphanie Lambert-Porcheron, Isabelle Dussous, Loïc Roger, Hugo Roume, Nathalie Galleron, Nicolas Pons, Emmanuelle Le Chatelier, Stanislav Dusko Ehrlich, Martine Laville, Joël Doré, Julie-Anne Nazare, CarMeN, laboratoire, Démonstrateurs - MetaGenoPolis - - MGP2011 - ANR-11-DPBS-0001 - DPBS - VALID, Intensity mapping of the atomic carbon CII line - CONCERTO - - Intensity mapping of the atomic carbon CII line: the promise of a new observational probe of dusty star-formation in post-reionization and reionization epoch2017-01-01 - 0000-00-00 - PE9, ERC-2017-ADG - VALID, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French-Clinical Research Infrastructure Network / F-CRIN [Lyon] (Cardiovascular & Renal Clinical Trialists - INI-CRCT ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bridor - Groupe LE DUFF [Rennes] (BGLD), This study was funded by Bridor and in part by Metagenopolis grant Agence Nationale de la Recherche ANR-11-DPBS-0001. JD acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Grant agreement ERC-2017-AdG No. 788191 - Homo.symbiosus). We thank all the subjects who participated in this study. We thank Bernard Henrissat who annotated the IGC2 with CAZy., ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011), European Project: PE9, ERC-2017-ADG, Intensity mapping of the atomic carbon CII line: the promise of a new observational probe of dusty star-formation in post-reionization and reionization epoch,Advanced Grant (AdG), PE9, ERC-2017-ADG,CONCERTO(2017), FCRIN/FORCE Network, Centre d'Edition Numérique Scientifique (CENS), École normale supérieure de Lyon (ENS de Lyon)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-CHU Grenoble-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)
Subjects: Microbiology (medical), Dietary Fiber, gut microbiota, [SDV]Life Sciences [q-bio], Gastroenterology, Dietary fiber diversity, Bread, Microbiology, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Infectious Diseases, Eisenbergiella sp, Cardiovascular Diseases, Parabacteroides distasonis, Metabolome, glycoside hydrolases, Humans, cardiometabolic profile
Abstract: International audience; Some cardiometabolic risk factors such as dyslipidemia and insulin resistance are known to be associated with low gut microbiota richness. A link between gut microbiota richness and the diversity of consumed dietary fibers (DF) has also been reported. We introduced a larger diversity of consumed DF by using a daily consumed bread in subjects at cardiometabolic risk and assessed the impacts on the composition and functions of gut microbiota as well as on cardiometabolic profile. Thirty-nine subjects at cardiometabolic risk were included in a double-blind, randomized, cross-over, twice 8-week study, and consumed daily 150 g of standard bread or enriched with a 7-dietary fiber mixture (5.55 g and 16.05 g of fibers, respectively). Before and after intervention, stool samples were collected for gut microbiota analysis from species determination down to gene-level abundance using shotgun metagenomics, and cardiometabolic profile was assessed. Multi-fiber bread consumption significantly decreased Bacteroides vulgatus, whereas it increased Parabacteroides distasonis, Fusicatenibacter saccharivorans, an unclassified Acutalibacteraceae and an unclassified Eisenbergiella (q \textless 0.1). The fraction of gut microbiota carrying the gene coding for five families/subfamilies of glycoside hydrolases (CAZymes) were also increased and negatively correlated with peaks and total/incremental area under curve (tAUC/iAUC) of postprandial glycemia and insulinemia. Compared to control bread, multi-fiber bread decreased total cholesterol (-0.42 mM; q \textless 0.01), LDL cholesterol (-0.36 mM; q \textless 0.01), insulin (-2.77 mIU/l; q \textless 0.05), and HOMA (-0.78; q \textless 0.05). In conclusion, increasing the diversity of DF in a daily consumed product modifies gut microbiota composition and function and could be a relevant nutritional tool to improve cardiometabolic profile.
Published: 2022
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14. [Investigation of large granular lymphocytic leukemias: data from the laboratory of hematology at Nancy University Hospital, France]

Author: Charles Guisnel, Jean-François Lesesve, Delphine Gérard, Sylvain Salignac, Marc Muller, Pierre Feugier, Julien Broséus, and Véronique Latger-Cannard
Subjects: Leukemia, Large Granular Lymphocytic, Humans, General Medicine, Hematology, Laboratories, Hospitals, Retrospective Studies
Abstract: Large granular lymphocytic leukemia (LGLL) is a rare clonal lymphoproliferative disorder from T or NK origin.to report on the diagnostic and therapeutic management of LGLL investigated in the university hospital at Nancy, France.retrospective (7 years) collection of clinical and biological data and patients' cohort analysis.Eight out of fifteen patients presented with neutropenia, including five profound neutropenia (neutrophils 500 × 10Although using simple and robust investigations, our series demonstrates a high heterogeneity in LGLL detection and assessment.
Published: 2022

15. Late Outcomes of Carotid Artery Stenting for Radiation Therapy-Induced Carotid Stenosis

Author: Bahaa Nasr, Valentin Crespy, Edouard Penasse, Marine Gaudry, Eugenio Rosset, Patrick Feugier, Yann Gouëffic, Blandine Maurel, Aurélien Hostalrich, Pierre Alric, Nirvana Sadaghianloo, Nicla Settembre, Jacques Chevallier, Sabrina Ben Ahmed, Pierre Gouny, Eric Steinmetz, Thierry Reix, Philippe Piquet, Edwin Ripoche, Olivier Rouviere, Michel Nonent, Jean-Christophe Gentric, Julien Ognard, Xavier Chaufour, Reda Hassen Khodja, Serge Bacard, Serguei Malikov, Raphaël Coscas, and Jean-Pierre Favre
Subjects: Endarterectomy, Carotid, Time Factors, Constriction, Pathologic, Coronary Restenosis, Treatment Outcome, Carotid Arteries, Recurrence, Risk Factors, Humans, Radiology, Nuclear Medicine and imaging, Surgery, Carotid Stenosis, Stents, Cardiology and Cardiovascular Medicine, Retrospective Studies
Abstract: Purpose: Carotid artery stenting (CAS) appears as a promising alternative treatment to carotid endarterectomy for radiation therapy (RT)-induced carotid stenosis. However, this is based on a poor level of evidence studies (small sample size, primarily single institution reports, few long-term data). The purpose of this study was to report the long-term outcomes of a multicentric series of CAS for RT-induced stenosis. Methods: All CAS for RT-induced stenosis performed in 11 French academic institutions from 2005 to 2017 were collected in this retrospective study. Patient demographics, clinical risk factors, elapsed time from RT, clinical presentation and imaging parameters of carotid stenosis were preoperatively gathered. Long-term outcomes were determined by clinical follow-up and duplex ultrasound. The primary endpoint was the occurrence of cerebrovascular events during follow-up. Secondary endpoints included perioperative morbidity and mortality rate, long-term mortality rate, primary patency, and target lesion revascularization. Results: One hundred and twenty-one CAS procedures were performed in 112 patients. The mean interval between irradiation and CAS was 15 ± 12 years. In 31.4% of cases, the lesion was symptomatic. Mean follow-up was 42.5 ± 32.6 months (range 1–141 months). The mortality rate at 5 years was 23%. The neurologic event-free survival and the in-stent restenosis rates at 5 years were 87.8% and 38.9%, respectively. Diabetes mellitus (p=0.02) and single postoperative antiplatelet therapy (p=0.001) were found to be significant predictors of in-stent restenosis. Freedom from target lesion revascularization was 91.9% at 5 years. Conclusion: This study showed that CAS is an effective option for RT-induced stenosis in patients not favorable to carotid endarterectomy. The CAS was associated with a low rate of neurological events and reinterventions at long-term follow-up.
Published: 2022

16. Obinutuzumab plus lenalidomide in advanced, previously untreated follicular lymphoma in need of systemic therapy: a LYSA study

Author: Emmanuel Bachy, Roch Houot, Pierre Feugier, Krimo Bouabdallah, Reda Bouabdallah, Emmanuelle Nicolas Virelizier, Marie Maerevoet, Christophe Fruchart, Sylvia Snauwaert, Steven Le Gouill, Jean-Pierre Marolleau, Lysiane Molina, Cécile Moluçon-Chabrot, Catherine Thieblemont, Hervé Tilly, Fontanet Bijou, Corinne Haioun, Eric Van den Neste, Bettina Fabiani, Michel Meignan, Guillaume Cartron, Gilles Salles, Olivier Casasnovas, Franck Morschhauser, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), French Innovative Leukemia Organization (Filo), CHU Bordeaux [Bordeaux], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Léon Bérard [Lyon], Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), CH Dunkerque, Department of ENT surgery, AZ Sint Jan Brugge Oostende, Service d'Hématologie Biologique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), L’Héma-NexT [UNIV Nantes] (i-Site NexT), Université de Nantes (UN), Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers (CRCI2NA ), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), CHU Amiens-Picardie, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), NF-kappaB, Différenciation et Cancer (OncokappaB (URP_7324)), Université Paris Cité (UPCité), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Bergonié [Bordeaux], UNICANCER, Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cliniques Universitaires Saint-Luc [Bruxelles], Service de neurophysiologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), LYSA Imaging (Créteil) (LYSA-IM), CHU Henri Mondor, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Weill Medical College of Cornell University [New York], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Lille, The study was funded by the LYSARC, and financially supported in part by investigator-initiated study grants from Celgene/BMS and Roche., Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Microenvironnement des niches tumorales [UNIV Tours] (CNRS GDR 3697 MicroNiT), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service de gastro-entérologie, and UCL - (SLuc) Unité d'oncologie médicale
Subjects: Adult, Neutropenia, Adolescent, [SDV]Life Sciences [q-bio], Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Biology, Hematology, Antibodies, Monoclonal, Humanized, Biochemistry, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols, Humans, Lenalidomide, Lymphoma, Follicular
Abstract: Obinutuzumab and lenalidomide (referred to as the GALEN combination) is an active immunomodulatory combination with a manageable safety profile in multiple types of lymphoma. We report efficacy and safety results for the phase 2 GALEN study in previously untreated patients with advanced follicular lymphoma (FL). Eligible patients aged ≥18 years had an Eastern Cooperative Oncology Group performance status ≤2 and high-tumor burden, grade 1 to 3a FL. Induction treatment was obinutuzumab (1000 mg IV, days 8, 15, and 22, cycle 1; day 1, cycles 2-6) plus lenalidomide (20 mg/d, days 1-21, cycle 1; days 2-22, cycles 2-6) for six 28-day cycles. Maintenance included obinutuzumab (1000 mg every 2 cycles) plus lenalidomide (10 mg, days 2-22) for ≤12 cycles (year 1) followed by obinutuzumab (1000 mg every 56 days) for 6 cycles (year 2). The primary end point was complete response rate (CRR) after induction per the 1999 International Working Group criteria. From October 2015 to February 2017, a total of 100 patients were enrolled. CRR after induction was 47%, and the overall response rate (ORR) was 92%. Post hoc analyses per the 2014 Lugano classification, including patients with missing bone marrow assessments, identified an additional 13 patients fulfilling CRR criteria, resulting in a complete metabolic response of 80% and an ORR of 94%. At a median follow-up of 3.7 years, 3-year progression-free survival and overall survival were 82% and 94%, respectively. The most common adverse event was neutropenia (48% any grade; 47% grade ≥3). Only 2% of patients presented with febrile neutropenia; others were mainly grade ≤2. No other specific grade ≥3 toxicity occurred at a frequency >3%. Overall, these results showed promising clinical efficacy for the chemotherapy-free GALEN backbone in previously untreated patients with high tumor burden FL. Except for neutropenia, the safety profile of the combination is remarkable. The study was registered at clinicaltrials.gov as #NCT01582776.
Published: 2022
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17. Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial

Author: Harimalala Ranaivo, Zhengxiao Zhang, Maud Alligier, Laurie Van Den Berghe, Monique Sothier, Stéphanie Lambert-Porcheron, Nathalie Feugier, Charlotte Cuerq, Christelle Machon, Audrey M. Neyrinck, Benjamin Seethaler, Julie Rodriguez, Martin Roumain, Giulio G. Muccioli, Véronique Maquet, Martine Laville, Stephan C. Bischoff, Jens Walter, Nathalie M. Delzenne, Julie-Anne Nazare, UCL - SSS/LDRI - Louvain Drug Research Institute, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French-Clinical Research Infrastructure Network / F-CRIN [Lyon] (Cardiovascular & Renal Clinical Trialists - INI-CRCT ), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Jimei University [Fujian, China] (JMU), Hospices Civils de Lyon (HCL), Louvain Drug Research Institute [Bruxelles, Belgique] (LDRI), Université Catholique de Louvain = Catholic University of Louvain (UCL), University of Hohenheim, KitoZyme SA [Herstal, Belgium.] (KZ), University College Cork (UCC), and CarMeN, laboratoire
Subjects: Blood Glucose, Dietary Fiber, Multidisciplinary, Bacteria, [SDV]Life Sciences [q-bio], digestive, oral, and skin physiology, Chitin, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Feces, Mice, Cardiovascular Diseases, RNA, Ribosomal, 16S, Dietary Supplements, Animals, Humans, Glucans
Abstract: Chitin-glucan (CG), an insoluble dietary fiber, has been shown to improve cardiometabolic disorders associated with obesity in mice. Its effects in healthy subjects has recently been studied, revealing its interaction with the gut microbiota. In this double-blind, randomized, cross-over, twice 3-week exploratory study, we investigated the impacts of CG on the cardiometabolic profile and gut microbiota composition and functions in 15 subjects at cardiometabolic risk. They consumed as a supplement 4.5 g of CG daily or maltodextrin as control. Before and after interventions, fasting and postprandial metabolic parameters and exhaled gases (hydrogen [H2] and methane [CH4]) were evaluated. Gut microbiota composition (16S rRNA gene sequencing analysis), fecal concentrations of bile acids, long- and short-chain fatty acids (LCFA, SCFA), zonulin, calprotectin and lipopolysaccharide binding protein (LBP) were analyzed. Compared to control, CG supplementation increased exhaled H2 following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge served at lunch. Of note, the decrease in postprandial glycemia was only observed in subjects with higher exhaled H2, assessed upon lactulose breath test performed at inclusion. CG decreased a family belonging to Actinobacteria phylum and increased 3 bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005 and Eubacterium ventriosum group. Fecal metabolites, inflammatory and intestinal permeability markers did not differ between groups. In conclusion, we showed that CG supplementation modified the gut microbiota composition and improved postprandial glycemic response, an early determinant of cardiometabolic risk. Our results also suggest breath H2 production as a non-invasive parameter of interest for predicting the effectiveness of dietary fiber intervention.
Published: 2022
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18. TP53 mutations at codon 234 are associated with chlorambucil treatment in chronic lymphocytic leukemia

Author: Lazarian, Grégory, Theves, Floriane, Hormi, Myriam, Letestu, Rémi, Eclache, Virginie, Bidet, Audrey, Cornillet-Lefebvre, Pascale, Davi, Frédéric, Delabesse, Eric, Estienne, Marie-Hélène, Etancelin, Pascaline, Kosmider, Olivier, Laibe, Sophy, Lode, Laurence, Muller, Marc, Nadal, Nathalie, Naguib, Dina, Pastoret, Cédric, Poulain, Stéphanie, Sujobert, Pierre, Veronese, Lauren, Imache, Samia, Lefebvre, Valérie, Cymbalista, Florence, Baran-Marszak, Fanny, Soussi, Thierry, Aurran, Thérese, Herbaux, Charles, Cartron, Guillaume, Dartigeas, Caroline, Delmer, Alain, Dupuis, Jehan, Dilhuydy, Marie, Ferrant, Emmanuelle, Feugier, Pierre, Genevieve, Franck, de Guibert, Sophie, Guieze, Romain, Leblond, Véronique, Levy, Vincent, Leprêtre, Stephane, Merabet, Fatiha, Michallet, Anne-Sophie, Nguyen-Khac, Florence, Quinquenel, Anne, Raynaud, Sophie, Re, Daniel, Thieblemont, Catherine, Tournillhac, Olivier, Troussard, Xavier, Truchan-Graczyk, Malgorzata, Willems, Lise, Ysebaert, Loic, Zini, Jean-Marc, Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Service d'Hématologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Biologique [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Service d'Hématologie biologique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Département d'Oncologie Génétique [Rouen] (CLCC Henri Becquerel), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Laboratoire Bio-Santis, Cavaillon, France, Laboratoire d'oncobiologie [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Génétique Médicale (CHU de Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Génétique Chromosomique et Moléculaire [CHU Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'hématologie biologique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pontchaillou [Rennes], Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hématologie Cellulaire [Hospices civils de Lyon], Hospices Civils de Lyon, Lyon, France, Hospices Civils de Lyon (HCL), Service de Cytogénétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Mort cellulaire programmée et résistance aux drogues dans les hémopathies malignes = Cell death and Drug Resistance in Hematological Disorders [CRC], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Uppsala University, French Innovative Leukemia Organization (Filo), Cancéropole Ille de France. Grant Number: 2019-1-EMERG-22-INSERM 6-1, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), and Gestionnaire, Hal Sorbonne Université
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Mutation, Humans, Chlorambucil, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Tumor Suppressor Protein p53, Codon, Leukemia, Lymphocytic, Chronic, B-Cell, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2022
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19. Positron emission tomography-imaging assessment for guiding strategy in patients with relapsed/refractory large B-cell lymphoma receiving CAR T cells

Author: Jean Galtier, Laetitia Vercellino, Loic Chartier, Pierre Olivier, Claire Tabouret-Viaud, Charles Mesguich, Roberta Di Blasi, Amandine Durand, Léo Raffy, François-Xavier Gros, Isabelle Madelaine, Veronique Meignin, Miryam Mebarki, Marie-Thérèse Rubio, Pierre Feugier, Olivier Casasnovas, Michel Meignan, Catherine Thieblemont, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), The Lymphoma Academic Research Organisation [Lyon] (LYSARC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHU Bordeaux [Bordeaux], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Université de Bordeaux (UB), Service d'Hématologie [CHRU Nancy], CHU Henri Mondor, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), and leboeuf, Christophe
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, Positron-Emission Tomography, T-Lymphocytes, Positron Emission Tomography Computed Tomography, Humans, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Lymphoma, Large B-Cell, Diffuse, Prognosis, Lactate Dehydrogenases, Retrospective Studies
Abstract: The aim of this study was to evaluate the prognostic impact of the F-fluorodeoxyglucose positron emission tomography response at 1 month (M1) and 3 months (M3) after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in a multicenter cohort of 160 patients with relapsed/refractory large B-cell lymphomas (R/R LBCL). In total, 119 (75%) patients reached M1 evaluation; 64 (53%, 64/119) had a complete response (CR); 91% were Deauville Score (DS) 1-3. Progressionfree survival (PFS) and overall survival (OS) were significantly worse in patients with DS-5 at M1, than in patients with DS 1-3 (PFS hazard ratio [HR]=6.37, 95% confidence interval [CI]: 3.5-11.5 vs. OS HR=3.79, 95% CI: 1.7-8.5) and DS-4 (PFS HR=11.99, 95% CI: 5.0-28.9 vs. OS HR=12.49, 95% CI: 2.8-55.8). The 1-year PFS rates were 78.9% (95% CI: 58.9-89.9) for DS-4 at M1, similar to 67.3% (95% CI: 51.8-78.8) for patients with DS 1-3 at M1, very different to 8.6% (95% CI: 1.8-22.4) for DS-5, respectively. Only eight of 30 (26%) patients with DS-4 progressed. Response at M3 evaluated in 90 (57%) patients was prognostic for PFS with lower discrimination (HR=3.28, 95% CI: 1.5-7.0; P=0.003) but did not predict OS (HR=0.61, 95% CI: 0.2-2.3; P=0.45). Patients with a high baseline total metabolic tumor volume (TMTV) >80 mL had worse PFS (HR=2.05, 95% CI: 1.2-3.5; P=0.009) and OS (HR=4.52, 95% CI: 2.5-8.1; P80 mL, and DS-5 at M1 for OS. In conclusion, baseline TMTV and response at M1 strongly predicts outcomes of patients with R/R LBCL undergoing CAR T-cell therapy.
Published: 2021
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20. Incidence of central nervous system relapses in patients with DLBCL treated with lenalidomide as maintenance after R-CHOP

Author: Koen Van Eygen, Richard Greil, René-Olivier Casasnovas, Catherine Thieblemont, Sophie Bernard, Samuel Griolet, Maria Gomes da Silva, Loïc Renaud, Hervé Ghesquières, Judith Trotman, Sebastian Grosicki, Christiane Copie-Bergman, Franck Morschhauser, Alejandro Martin Garcia-Sancho, Pierre Feugier, and Corinne Haioun
Subjects: Oncology, Central Nervous System, medicine.medical_specialty, business.industry, Incidence (epidemiology), Incidence, Central nervous system, Hematology, medicine.disease, Text mining, medicine.anatomical_structure, Internal medicine, medicine, Research Letter, Humans, In patient, Lymphoma, Large B-Cell, Diffuse, Neoplasm Recurrence, Local, business, Diffuse large B-cell lymphoma, Lenalidomide, medicine.drug
Published: 2021

21. Multiscale bio-chemo-mechanical model of intimal hyperplasia

Author: Jérôme Jansen, Xavier Escriva, Fabien Godeferd, and Patrick Feugier
Subjects: Hyperplasia, Mechanical Engineering, Modeling and Simulation, Hemodynamics, Humans, Arteries, Collagen, Models, Theoretical, Biotechnology
Abstract: We consider a computational multiscale framework of a bio-chemo-mechanical model for intimal hyperplasia. With respect to existing models, we investigate the interactions between hemodynamics, cellular dynamics and biochemistry on the development of the pathology. Within the arterial wall, we propose a mathematical model consisting of kinetic differential equations for key vascular cell types, collagen and growth factors. The luminal hemodynamics is modeled with the Navier-Stokes equations. Coupling hypothesis among time and space scales are proposed to build a tractable modeling of such a complex multifactorial and multiscale pathology. A one-dimensional numerical test-case is presented for validation by comparing the results of the framework with experiments at short and long timescales. Our model permits to capture many cellular phenomena which have a central role in the physiopathology of intimal hyperplasia. Results are quantitatively and qualitatively consistent with experimental findings at both short and long timescales.
Published: 2021

22. Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study

Author: Roch Houot, Guillaume Cartron, Corinne Haioun, Véronique Meignin, Danielle Canioni, Pierre Feugier, Gilles Salles, Sylvia Snauwaert, Emmanuelle Nicolas-Virelizier, Ka Lung Wu, Franck Morschhauser, Christophe Fruchart, Sarah Bailly, Fontanet Bijou, Christophe Bonnet, Reda Bouabdallah, Koen Van Eygen, Catherine Thieblemont, Hervé Tilly, Steven Le Gouill, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Institut Bergonié [Bordeaux], UNICANCER, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, C.A.Z. Groeninge, Department of ENT surgery, AZ Sint Jan Brugge Oostende, Université de Liège, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hématologie-oncologie adultes, 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), Hopital Saint-Louis [AP-HP] (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Ziekenhuis Netwerk Antwerpen (ZNA), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Rennes (UR)-Hôpital Pontchaillou, Centre Hospitalier Universitaire [Rennes], UCL - SSS/DDUV/SIGN - Cell signalling, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Service d'hématologie, Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Follicular lymphoma, et Celgene et Roche, chemistry.chemical_compound, Antineoplastic Agents, Immunological, 0302 clinical medicine, Recurrence, Obinutuzumab, Lenalidomide, Lymphoma, Follicular, Aged, 80 and over, education.field_of_study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, Survival Rate, Treatment Outcome, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, Lymphoma Academic Research Organization, Refractory Follicular Lymphoma, medicine.drug, Adult, medicine.medical_specialty, Lymphoma, B-Cell, Neutropenia, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Humanized, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, medicine, Humans, education, Survival rate, Aged, business.industry, Antigens, CD20, medicine.disease, chemistry, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Febrile neutropenia, 030215 immunology
Abstract: Summary Background Lenalidomide plus rituximab is approved to treat patients with relapsed or refractory follicular lymphoma. Obinutuzumab has been shown to enhance antibody-dependent cellular cytotoxicity, phagocytosis, and direct B-cell killing better than rituximab. Our aim was to determine the activity and safety of lenalidomide plus obinutuzumab in previously treated patients with relapsed or refractory follicular lymphoma. Methods In this multicentre, single-arm, phase 2 study, patients were enrolled from 24 Lymphoma Academic Research Organisation centres in France. Eligible patients (age ≥18 years) had histologically confirmed CD20-positive relapsed or refractory follicular lymphoma of WHO grade 1, 2, or 3a; an ECOG performance status of 0–2; and received at least one previous rituximab-containing therapy. Patients received oral lenalidomide (20 mg) plus intravenously infused obinutuzumab as induction therapy (1000 mg; six 28-day cycles), 1-year maintenance with lenalidomide (10 mg; 12 28-day cycles; days 2–22) plus obinutuzumab (1000 mg; alternate cycles), and 1-year maintenance with obinutuzumab (1000 mg; six 56-day cycles; day 1). The primary endpoint was the proportion of patients who achieved an overall response at induction end as per investigator assessment using the 1999 international working group criteria. The secondary endpoints were event-free survival, progression-free survival, overall survival, and safety. Analyses were per-protocol; the efficacy population included all patients who received at least one dose of both obinutuzumab and lenalidomide, and the safety population included all patients who received one dose of either investigational drug. The study is registered with ClinicalTrials.gov , number NCT01582776 , and is ongoing but closed to accrual. Findings Between June 11, 2014, and Dec 18, 2015, 89 patients were recruited and 86 patients were evaluable for efficacy and 88 for safety. Median follow-up was 2·6 years (IQR 2·2–2·8). 68 (79%) of 86 evaluable patients (95% CI 69–87) achieved an overall response at induction end, meeting the prespecified primary endpoint. At 2 years, event-free survival was 62% (95% CI 51–72), progression-free survival 65% (95% CI 54–74), duration of response 70% (95% CI 57–79), and overall survival 87% (95% CI 78–93). Complete response was achieved by 33 (38%, 95% CI 28–50) of 86 patients at induction end, and the proportion of patients achieving a best overall response was 70 (81%, 95% CI 72–89) and 72 (84%, 74–91) of 86 patients during induction and treatment, respectively. The most common adverse events were asthenia (n=54, 61%), neutropenia (n=38, 43%), bronchitis (n=36, 41%), diarrhoea (n=35, 40%), and muscle spasms (n=34, 39%). Neutropenia was the most common toxicity of grade 3 or more; four (5%) patients had febrile neutropenia. 57 serious adverse events were reported in 30 (34%) of 88 patients. The most common serious adverse events were basal cell carcinoma (n=5, 6%), febrile neutropenia (n=4, 5%), and infusion-related reaction (n=3, 3%). One patient died due to treatment-related febrile neutropenia. Interpretation Our data shows that lenalidomide plus obinutuzumab is active in previously treated patients with relapsed or refractory follicular lymphoma, including those with early relapse, and has a manageable safety profile. Randomised trials of new immunomodulatory regimens, such as GALEN or using GALEN as a backbone, versus lenalidomide plus rituximab, are warranted. Funding Lymphoma Academic Research Organisation, and Celgene and Roche
Published: 2019
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23. Sustained Progression-Free Survival Benefit of Rituximab Maintenance in Patients With Follicular Lymphoma: Long-Term Results of the PRIMA Study

Author: Andrew Lister, Maria Gomes da Silva, John F. Seymour, Harald Zeuner, Jonathan Farhi, John Catalano, Véronique Dorvaux, Sirpa Leppä, David Simpson, Loic Ysebaert, Steven Le Gouill, David Belada, Anne Sonet, Emmanuel Bachy, Pauline Brice, Luc Xerri, Tanin Intragumtornchai, Lars Møller Pedersen, Anne Vekhoff, Sylvie Glaisner, Jane Estell, Gilles Salles, Alejandro Martín, Hervé Tilly, Olivier Casasnovas, François Lemonnier, Fritz Offner, Jean Gabarre, Armando López-Guillermo, Gustavo Milone, Pierre Feugier, Department of Oncology, HUS Comprehensive Cancer Center, and University of Helsinki
Subjects: Oncology, Male, Cancer Research, Time Factors, Follicular lymphoma, THERAPY, 0302 clinical medicine, Antineoplastic Agents, Immunological, Prednisone, CYCLOPHOSPHAMIDE, Lymphoma and Myeloma, Lymphoma, Follicular, R-CVP, Aged, 80 and over, Middle Aged, CHEMOTHERAPY, Progression-Free Survival, 3. Good health, 030220 oncology & carcinogenesis, Disease Progression, Rituximab, Female, TRIAL, medicine.drug, Adult, PREDNISONE, medicine.medical_specialty, Vincristine, Cyclophosphamide, 3122 Cancers, 03 medical and health sciences, Young Adult, Internal medicine, RAPID COMMUNICATIONS, medicine, Humans, Progression-free survival, NON-HODGKINS-LYMPHOMA, VINCRISTINE, Watchful Waiting, Aged, business.industry, medicine.disease, PHASE-III, Lymphoma, Clinical trial, business, RESPONSE DURATION, 030215 immunology
Abstract: PURPOSE The PRIMA study (ClinicalTrials.gov identifier: NCT00140582 ) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety. METHODS Patients (> 18 years of age) with previously untreated high–tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m2, once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016). RESULTS In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P < .001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed. CONCLUSION Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.
Published: 2019

24. Treatment of Complex Aortic Aneurysms Using Combination of Renal and Visceral Bypass and Fenestrated/Branched Stent Grafts

Author: Patrick Feugier, Eugenio Rosset, Sabrina Ben Ahmed, Bertrand Chavent, Nellie Della Schiava, Ambroise Duprey, Jean-Pierre Favre, Jean-Noël Albertini, Service de Chirurgie Thoracique Vasculaire [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], and CHU Clermont-Ferrand-CHU Clermont-Ferrand
Subjects: medicine.medical_specialty, Time Factors, Computed Tomography Angiography, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030204 cardiovascular system & hematology, Prosthesis Design, Aortography, Endovascular aneurysm repair, 030218 nuclear medicine & medical imaging, Blood Vessel Prosthesis Implantation, 03 medical and health sciences, Aortic aneurysm, Postoperative Complications, Renal Artery, 0302 clinical medicine, Aneurysm, Risk Factors, medicine.artery, medicine, Humans, Renal artery, Aorta, Aortic Aneurysm, Thoracic, business.industry, Endovascular Procedures, Stent, General Medicine, medicine.disease, Abdominal aortic aneurysm, Blood Vessel Prosthesis, 3. Good health, Surgery, Viscera, Treatment Outcome, Bypass surgery, cardiovascular system, Stents, France, Cardiology and Cardiovascular Medicine, business, Aortic Aneurysm, Abdominal
Abstract: Background The purpose of this study was to report our experience of treatment of aortic aneurysms using combination of renal and visceral arteries bypasses and fenestrated/branched stent graft in various complex anatomical situations. Methods Between November 2005 and March 2017, 10 patients underwent a hybrid strategy combining bypasses for renal and/or visceral arteries and custom-made fenestrated/branched stent grafts. Two patients had abdominal aortic aneurysm (1 juxtarenal and 1 suprarenal), and 8 patients had thoracoabdominal aortic aneurysm (1 type I, 2 type II including one dissection, 2 type III, 1 type IV, and 2 type V). In total, 37 renal and visceral arteries were targeted, of which 23 were treated using fenestrated or branched stent graft and 14 were treated by bypass (11 to renal artery and 3 to celiac trunk). Results Technical success was 100%, and no patient died during a mean follow-up of 24.3 ± 21 months. Six patients had 7 postoperative complications after bypass surgery, and 3 patients had 3 complications after fenestrated or branched endovascular aneurysm repair (FEVAR/BEVAR) procedure. Seven reinterventions were performed in 3 patients. No occlusion of target vessels occurred. Renal function was stable during follow-up in all patients except one who developed end-stage renal failure requiring permanent dialysis. On the last follow-up computed tomography scan, aneurysm diameter decreased for 6 patients, was stable for 3 patients, and increased for one patient, in which persistent type II endoleak was observed. Aneurysm exclusion was complete in the remaining 9 patients. Conclusions Combination of FEVAR/BEVAR procedures with renal and/or visceral artery bypass in patients with complex aortic aneurysms is feasible with acceptable results. Morbidity associated with bypass surgery has to be carefully balanced with the risk of catheterization difficulties in the setting of adverse anatomical features of the visceral/renal arteries or the aorta.
Published: 2019
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25. Functional pathways associated with human carotid atheroma: a proteomics analysis

Author: Rui Zhu, Ali Nehme, Firas Kobeissy, Jingfu Zhao, Yehia Mechref, Kazem Zibara, and Patrick Feugier
Subjects: Carotid Artery Diseases, Male, Proteomics, Vascular smooth muscle, Physiology, 030204 cardiovascular system & hematology, Biology, Muscle, Smooth, Vascular, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Transforming Growth Factor beta, Internal Medicine, Humans, Gene Regulatory Networks, 030212 general & internal medicine, Gene, Transcription factor, Cytoskeleton, Aged, Aged, 80 and over, Endarterectomy, Carotid, Messenger RNA, Gene Expression Profiling, Computational Biology, Middle Aged, Plaque, Atherosclerotic, Extracellular Matrix, High-Throughput Screening Assays, Cell biology, Gene Expression Regulation, Proteome, Female, Cardiology and Cardiovascular Medicine, Extracellular matrix organization
Abstract: Advances in large-scale analysis are becoming very useful in understanding health and disease. Here, we used high-throughput mass spectrometry to identify differentially expressed proteins between early and advanced lesions. Carotid endarterectomy samples were collected and dissected into early and advanced atherosclerotic lesion portions. Proteins were extracted and subjected to liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. Differentially expressed proteins were identified and verified using multiple reaction monitoring (MRM), on which advanced systems biology and enrichment analyses were performed. The identified proteins were further compared to the transcriptomic data of 32 paired samples obtained from early and advanced atherosclerotic lesions. A total of 95 proteins were upregulated, and 117 proteins were downregulated in advanced lesions compared to early atherosclerotic lesions (p
Published: 2019
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26. Clinical, biological, and molecular genetic features of Richter syndrome and prognostic significance: a study of the French Innovative Leukemia Organization

Author: Reiner Siebert, Anne Quinquenel, Romain Guieze, Catherine Thieblemont, Frederic Davi, Caroline Dartigeas, Sébastien Hergalant, Mathilde Hunault, Florence Cymbalista, Christof Schneider, Marie-Christine Béné, Cécile Tomowiak, Thomas Remen, Kamel Laribi, Damien Roos-Weil, Julien Broséus, Gregory Lazarian, Francis Guillemin, Odile Blanchet, Florian Bouclet, Elise Chapiro, Eugen Tausch, Stephan Stilgenbauer, Sandra Lomazzi, Florence Nguyen-Khac, Pierre Feugier, Charline Moulin, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département Méthodologie Promotion Investigation [CHRU Nancy] (MPI), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Universitaire de Reims (CHU Reims), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Ulm - Ulm University [Ulm, Allemagne], Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), 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), Centre de Ressources Biologiques - [Nancy] (CRB Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hergalant, Sébastien, 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: Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Richter syndrome, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Medicine, Humans, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Hematology, medicine.disease, Prognosis, Survival Analysis, 3. Good health, [STAT] Statistics [stat], [STAT]Statistics [stat], Leukemia, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 030220 oncology & carcinogenesis, Cytogenetic Analysis, Mutation, Disease Progression, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Lymphoma, Large B-Cell, Diffuse, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business
Abstract: International audience
Published: 2021
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27. Real-world outcomes following venetoclax therapy in patients with chronic lymphocytic leukemia or Richter syndrome: a FILO study of the French compassionate use cohort

Author: Sophie de Guibert, Lauren Veronese, Loic Ysebaert, Charles Herbaux, Olivier Tournilhac, Emmanuelle Tchernonog, Anne-Sophie Michallet, Florence Cymbalista, Damien Roos-Weil, Bruno Pereira, Jehan Dupuis, Pierre Feugier, Anne Calleja, Florian Bouclet, Caroline Dartigeas, Sandy Amorim, Anaise Blouet, Marie-Sarah Dilhuydy, Florence Nguyen-Khac, Pierre Morel, Nataliya Dmytruck, Kamel Laribi, Alain Delmer, Thérèse Aurran, Bénédicte Hivert, Romain Guieze, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), and FAYE, Fatimata
Subjects: Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Compassionate Use Trials, Male, medicine.medical_treatment, Chronic lymphocytic leukemia, Abnormal Karyotype, Kaplan-Meier Estimate, Targeted therapy, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Medicine, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Sulfonamides, Hematology, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Middle Aged, Progression-Free Survival, 3. Good health, Tumor lysis syndrome, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Female, France, Lymphoma, Large B-Cell, Diffuse, Adult, medicine.medical_specialty, Antineoplastic Agents, Infections, 03 medical and health sciences, Internal medicine, Complex Karyotype, Humans, Aged, Retrospective Studies, business.industry, Venetoclax, medicine.disease, Bridged Bicyclo Compounds, Heterocyclic, Genes, p53, Leukemia, Lymphocytic, Chronic, B-Cell, chemistry, Drug Evaluation, business, Tumor Lysis Syndrome, 030215 immunology
Abstract: The BCL2 inhibitor venetoclax is transforming the management of patients with chronic lymphocytic leukemia (CLL), given its high efficacy in relapsed/refractory CLL as observed in both early-phase and randomized clinical trials. The present study aimed to determine whether venetoclax is effective and well tolerated in patients with CLL or Richter's syndrome (RS) in a real-world setting and to highlight factors impacting survival. Data from a venetoclax French compassionate use program were collected for 67 patients (60 with CLL and 7 with RS). Most patients presented adverse genetic features, such as TP53 disruption (74%) or complex karyotype (58%). Tumor lysis syndrome was observed in 14 (22%) patients, and 16 (24%) patients were hospitalized for grade III/IV infection. In the CLL cohort, ORR was 75 %, 1-year PFS was 61% (95% CI = 47-72%) and 1-year OS 70% (95% CI = 56-80%). No impact of TP53 disruption was noted while complex karyotype was identified as a predictor of both inferior PFS (HR = 3.46; 95% CI = 1-12; log-rank p = 0.03) and OS (HR = 3.2; 95% CI = 0.9-11.4, log-rank p = 0.047). Among the seven patients with RS, two achieved an objective response to venetoclax; however, the median OS was only 1.1 month. The well-balanced safety/efficacy profile of venetoclax is confirmed in this real-world setting. Complex karyotype should be evaluated as a predictive factor of survival for patients treated by venetoclax.
Published: 2021
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28. Transforming growth factor-β1 inhibits interleukin-1β-induced expression of inflammatory genes and Cathepsin S activity in human vascular smooth muscle cells

Author: Nedra Dhaouadi, Patrick Feugier, Wissam H. Faour, Jacques-Yuan Li, Catherine Cerutti, Ali H. Eid, Kazem Zibara, Ali Nehme, and Kamel Kacem
Subjects: Pharmacology, Vascular smooth muscle, biology, Chemistry, Interleukin-1beta, Interleukin, 030226 pharmacology & pharmacy, Molecular biology, Cathepsins, Muscle, Smooth, Vascular, Transforming Growth Factor beta1, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Transforming Growth Factor beta, CXCL6, biology.protein, Humans, Pharmacology (medical), Neutralizing antibody, Interleukin 1 receptor, type I, 030217 neurology & neurosurgery, Cells, Cultured, Cathepsin S, Transforming growth factor
Abstract: Objective and design This study investigated the opposite mechanisms by which IL-1β and TGF-β1 modulated the inflammatory and migratory phenotypes in cultured human intimal vascular smooth muscle cells vSMCs. Materials and treatment Primary human vSMCs, obtained from twelve hypertensive patients who underwent carotid endarterectomy, were incubated for 24 hours with either 40 pM TGF-β1, or 1 nmol/L IL-1β, or their combination in presence or absence of anti-TGF-β neutralizing antibody. Methods The expression levels of matrix metalloproteases and their inhibitors, and the elastolytic enzyme cathepsin S (CTSS) and its inhibitor cystatin C were evaluated with RT-PCR. CTSS activity was measured by fluorometry. Results TGF-β1 reversed IL-1β-induced expression of iNOS, CXCL6, IL1R1, MMP12, and CTSS, while upregulated TIMP2 expression. Furthermore, anti-TGF-β neutralizing antibody abrogated TGF-β effects. Combination with IL-1β and TGF-β1 induced the expression of IL1α, IL1β, IL1R1, and CTSS, but suppressed CST3 expression. CTSS expression in the combination treatment was higher than that of cells treated with anti-TGF-β antibodies alone. Moreover, IL-1β-induced CTSS enzymatic activity was reduced when human vSMCs were co-treated with TGF-β, whereas this reduction was abrogated by anti-TGF-β neutralizing antibody. Conclusion TGF-β1 abrogated IL-1β-induced expression of inflammatory genes and elastolytic activity in cultured human vSMCs. Thus, TGF-β1 can play a crucial role in impairing IL-1β-induced vascular inflammation and damage involved in the etiology of cardiovascular diseases.
Published: 2021

29. Clinical and biological characteristics of leukemia cutis in chronic lymphocytic leukemia: A study of the French innovative leukemia organization (FILO)

Author: Anne Lavaud, Audrey Bidet, Damien Roos-Weil, Benjamin Carpentier, Stéphane Leprêtre, Antoine Martin, Lauren Veronese, Alain Delmer, Loic Ysebaert, Bénédicte Hivert, Julien Broséus, Anne Corby, Eric Van Den Neste, Stéphanie Poulain, Agathe Waultier Rascalou, Kamel Laribi, Damien Luque Paz, Romain Guieze, Lise Willems, Jérôme Paillassa, Fatiha Merabet, Jean-Philippe Vial, Fanny Baran-Marszak, Pierre Feugier, Albane Ledoux-Pilon, Anne Quinquenel, Michaël Munger, Florence Cymbalista, Virginie Eclache, Eve Maubec, Chloé Friedrich, Marie-Sarah Dilhuydy, Lysiane Molina, Grégory Lazarian, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre du cancer, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Hôpital de l'Enfant-Jésus [CHU Québec] (HEJ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut de Cancérologie du GARD ICG - CHU Nîmes (Instit Cancéro - GARD), CRHU Nancy, Unité clinique de pathologie neuromusculaire [CHU Pitié-Salpêtrière], Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Hospitalier Le Mans (CH Le Mans), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cliniques Universitaires Saint-Luc [Bruxelles], Centre Hospitalier de la Rochelle (CH la Rochelle), Centre de Biologie Pathologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Avicenne [AP-HP], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), FAYE, Fatimata, Signalisation, Microenvironnement et Hémopathies Lymphoïdes B (SIMHEL), Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord-Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Oncology, Adult, Male, medicine.medical_specialty, Skin Neoplasms, Chronic lymphocytic leukemia, Internal medicine, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, Skin, Aged, 80 and over, B-Lymphocytes, business.industry, Leukemia cutis, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Leukemia, Treatment Outcome, Mutation, Female, France, medicine.symptom, business
Abstract: TO THE EDITOR : Patients with chronic lymphocytic leukemia (CLL) exhibit a variety of skin lesions including mostly non-specific cutaneous manifestations (such as cutaneous infections or exaggerated reactions to insect bite) and secondary cutaneous malignancies, as patients are at high risk of developing basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma. Specific cutaneous infiltration by neoplastic B lymphocytes with clinically identifiable skin lesions, also called leukemia cutis (LC), is more uncommon and has seldom been reported in chronic lymphocytic leukemia. [...]
Published: 2021
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30. Oxaliplatin before autologous transplantation in combination with high-dose cytarabine and rituximab provides longer disease control than cisplatin or carboplatin in patients with mantle-cell lymphoma: results from the LyMA prospective trial

Author: Olivier Casasnovas, Thierry Lamy, Catherine Thieblemont, Pierre Feugier, Clementine Joubert, Steven Le Gouill, Kamal Bouadballah, Remy Gressin, Hervé Tilly, Anne Moreau, Emmanuel Gyan, Gandhi Damaj, Hervé Maisonneuve, Olivier Hermine, Benoit Tessoulin, François Lemonnier, Lucie Oberic, David Chiron, Hacene Zerazhi, Vincent Ribrag, Eric Van Den Neste, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Centre du cancer, UCL - (SLuc) Unité d'oncologie médicale, UCL - (SLuc) Service de gastro-entérologie, 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Bordeaux [Bordeaux], Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], CHU Grenoble, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Henri Duffaut (Avignon), Hôpital Henri Mondor, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, The Lymphoma Academic Research Organisation [Lyon] (LYSARC), Cliniques Universitaires Saint-Luc [Bruxelles], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Chard-Hutchinson, Xavier
Subjects: Oncology, Adult, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Lymphoma, Mantle-Cell, Transplantation, Autologous, Disease-Free Survival, Carboplatin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Autologous stem-cell transplantation, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Autologous transplantation, Humans, Prospective Studies, Transplantation, business.industry, Cytarabine, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, 3. Good health, Oxaliplatin, [SDV] Life Sciences [q-bio], chemistry, 030220 oncology & carcinogenesis, Mantle cell lymphoma, Rituximab, Cisplatin, business, 030215 immunology, medicine.drug
Abstract: National audience; LyMA trial has demonstrated the benefit of rituximab maintenance after autologous stem cell transplantation (ASCT) in previously untreated mantle-cell lymphoma patients (MCL). Induction consisted of four courses of R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and platinum derivative). The platinum derivative (PD) choice was free: R-DHA-cisplatin, R-DHA-carboplatin, or R-DHA-oxaliplatin. We investigated the prognostic impact of each PD. PFS and OS calculated from inclusion and investigated in an intention-to-treat (ITT) (= 298) and per-protocol analyses (PP) (n = 227). R-DHACis, R-DHACa, or R-DHAOx were used at first cycle in 184, 76, and 38 patients, respectively. Overall, 71 patients (59 in the R-DHACis) required a change in PD, mainly because of PD toxicity. In ITT-analysis, PFS in the R-DHACis and R-DHACa groups were similar (4-year PFS of 65%), while R-DHAOx had a better PFS (4-year PFS of 65% versus 86.5%, respectively, HR = 0.44, p = 0.02). The 4-year OS was 92% for R-DHAOx versus 75.9% for R-DHACis/DHACa (HR = 0.37, p = 0.03). Similar results were yielded in the PP analysis. Low MIPI and R-DHAOx were independent favorable prognostic markers for both PFS (HR = 0.44, p = 0.035) and OS (HR = 0.36, p = 0.045). In vitro and in silico analyses confirmed that oxaliplatin has an anti-MCL cytotoxic effect that differs from that of other PD. R-DHAOx before ASCT provides better outcome in transplantation eligible young MCL patients.
Published: 2021
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31. Microenvironment Remodeling and Subsequent Clinical Implications in Diffuse Large B-Cell Histologic Variant of Richter Syndrome

Author: Hélène Augé, Anne-Béatrice Notarantonio, Romain Morizot, Anne Quinquenel, Luc-Matthieu Fornecker, Sébastien Hergalant, Pierre Feugier, Julien Broséus, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Institut de Cancérologie de Strasbourg Europe (ICANS), and Hergalant, Sébastien
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Lymphocyte, Chronic lymphocytic leukemia, Aggressive lymphoma, Review, Immune checkpoint inhibitor, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Tumor Microenvironment, Immunology and Allergy, Medicine, [INFO.INFO-DB] Computer Science [cs]/Databases [cs.DB], [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, 3. Good health, Neoplasm Proteins, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Lymphoma, Large B-Cell, Diffuse, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Signal Transduction, lcsh:Immunologic diseases. Allergy, Immunology, diffuse large B-cell lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], genomics, Humans, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, immune checkpoint, B cell, Tumor microenvironment, [INFO.INFO-DB]Computer Science [cs]/Databases [cs.DB], business.industry, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, microenvironment, Immune checkpoint, Lymphoma, Richter syndrom, Cancer research, chronic lymphocytic leukemia, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Richter syndrome, business, lcsh:RC581-607, Diffuse large B-cell lymphoma, 030215 immunology
Abstract: IntroductionRichter Syndrome (RS) is defined as the development of an aggressive lymphoma in the context of Chronic Lymphocytic Leukemia (CLL), with a Diffuse Large B-Cell Lymphoma (DLBCL) histology in 95% cases. RS genomic landscape shares only a few features with de novo DLBCLs and is marked by a wide spectrum of cytogenetic abnormalities. Little is known about RS microenvironment. Therapeutic options and efficacy are limited, leading to a 12 months median overall survival. The new targeted treatments usually effective in CLL fail to obtain long-term remissions in RS.MethodsWe reviewed available PubMed literature about RS genomics, PD-1/PD-L1 (Programmed Death 1/Programmed Death Ligand 1) pathway triggering and subsequent new therapeutic options.ResultsData from about 207 patients from four landmark papers were compiled to build an overview of RS genomic lesions and point mutations. A number of these abnormalities may be involved in tumor microenvironment reshaping. T lymphocyte exhaustion through PD-L1 overexpression by tumor cells and subsequent PD-1/PD-L1 pathway triggering is frequently reported in solid cancers. This immune checkpoint inhibitor is also described in B lymphoid malignancies, particularly CLL: PD-1 expression is reported in a subset of prolymphocytes from the CLL lymph node proliferation centers. However, there is only few data about PD-1/PD-L1 pathway in RS. In RS, PD-1 expression is a hallmark of recently described « Regulatory B-cells », which interact with tumor microenvironment by producing inhibiting cytokines such as TGF-β and IL-10, impairing T lymphocytes anti-tumoral function. Based upon the discovery of high PD-1 expression on tumoral B lymphocyte from RS, immune checkpoint blockade therapies such as anti-PD-1 antibodies have been tested on small RS cohorts and provided heterogeneous but encouraging results.ConclusionRS genetic landscape and immune evasion mechanisms are being progressively unraveled. New protocols using targeted treatments such as checkpoint inhibitors as single agents or in combination with immunochemotherapy are currently being evaluated.
Published: 2020
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32. Graft vasculopathy in upper extremity allotransplantation: Results of a retrospective high‐resolution ultrasonographic study

Author: L. Badet, Emmanuel Morelon, Jean Kanitakis, Palmina Petruzzo, Patrick Feugier, Stephane Luong, Aram Gazarian, Fabrice Danjou, and Claudia Sardu
Subjects: Male, Vascularized Composite Allotransplantation, Transplantation, business.industry, medicine.medical_treatment, Significant difference, Healthy subjects, High resolution, musculoskeletal system, Upper Extremity, Intimal media thickness, cardiovascular system, medicine, Humans, Vascular Diseases, Ultrasonography, business, Nuclear medicine, Retrospective Studies, Allotransplantation
Abstract: Graft vasculopathy (GV) is the most severe pathologic change of chronic rejection in vascularized composite allotransplantation. Since 2012, the intimal media thickness (IMT) of radial and ulnar arteries was annually monitored by high-resolution ultrasonography in seven bilateral upper extremity transplant (UET) patients. We also investigated the IMT of seven matched healthy subjects (controls). No significant difference between IMT values of controls and UET patients was found. The median IMT values of recipient radial and ulnar arteries were 0.23 mm and 0.25 mm, respectively, while the median IMT values of grafted radial and ulnar arteries were 0.27 mm and 0.30 mm, respectively. There was a statistically significant difference in the IMT values of the grafted and recipient ulnar arteries (p = .043), but this difference was no longer significant when patient #2 was excluded. He showed a significant difference between recipient and grafted arteries and significantly higher IMT values (p = .001) of his grafted arteries compared with those of all transplanted patients. This patient developed GV leading to graft loss 11 years after the transplantation. In conclusion, this study showed a significant IMT increase in an UET recipient who developed GV.
Published: 2020
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33. Characteristics of Lymphoma in Patients with Inflammatory Bowel Disease: A Systematic Review

Author: Tunay Kökten, Pierre Feugier, Ndeye Coumba Ndiaye, Silvio Danese, Catherine Thieblemont, Laurent Beaugerie, Rémi Houlgatte, Laurent Peyrin-Biroulet, Djésia Arnone, Julien Broséus, Marie Muller, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie [CHRU Nancy], Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Humanitas Clinical and Research Center [Rozzano, Milan, Italy]
Subjects: medicine.medical_specialty, Lymphoma, [SDV]Life Sciences [q-bio], Population, Follicular lymphoma, Lymphoproliferative disorders, Gastroenterology, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Humans, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, business.industry, MALT lymphoma, General Medicine, medicine.disease, Inflammatory Bowel Diseases, Prognosis, digestive system diseases, 3. Good health, Lymphatic system, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Complication, business
Abstract: Background Lymphoma is a dreaded complication of inflammatory bowel diseases [IBD]. Knowledge about lymphoma in patients with IBD is limited to epidemiological data and the description of risk factors. We performed a systematic review to describe the clinical characteristics and prognosis of lymphoma in patients with IBD. Methods Electronic databases were searched up to June 1, 2020. All published clinical characteristics of lymphoma occurring in patients with IBD were collected. Results Eleven studies were included. A total of 589 lymphomas were described in patients with IBD. As seen in de novo lymphoma, non-Hodgkin’s lymphoma [NHL] was the most common histological subtype [83.9%]. Diffuse large B-cell lymphoma [DLBCL] and follicular lymphoma were the most well-represented NHL in patients with IBD [30% and 13% respectively]. Two main differences were observed in comparison with de novo lymphoma: primary intestinal lymphoma [PIL] represented a large proportion of lymphoma in patients with IBD [22–75%] whereas mucosa-associated lymphoid tissue [MALT] lymphoma was under-represented. Epstein–Barr virus [EBV]-positive status was observed in a large proportion of tumours [44–75%]. Survival data of lymphoma in patients with IBD were similar to those of de novo lymphoma. Discussion This systematic review first highlights that PIL [especially DLBCL subtype] is significantly more frequent in patients with IBD and represents the most common entity. Conversely, MALT lymphoma is extremely rare in the IBD population. However, the overall quality of the evidence is low. Further studies are required to better define lymphoma characteristics in patients with IBD.
Published: 2020
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34. Lenalidomide/rituximab induces high molecular response in untreated follicular lymphoma: LYSA ancillary RELEVANCE study

Author: Hervé Tilly, Thierry Fest, Loic Ysebaert, Sylvie Glaisner, Guillaume Cartron, Rene-Olivier Casasnovas, Steven Le Gouill, Jean-Claude Eisenmann, Roch Houot, Marie-Hélène Delfau-Larue, Marie-Laure Boulland, Gilles Salles, Gian Matteo Pica, Franck Morschhauser, Asma Beldi-Ferchiou, François Lemonnier, Pierre Feugier, Luc Xerri, Pascal Godmer, Vincent Ribrag, Hervé Maisonneuve, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pontchaillou [Rennes], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Henri Mondor, Centre Hospitalier Métropole Savoie [Chambéry], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), 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), Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CRLCC René Huguenin, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, 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), CHU Montpellier, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bernardo, Elizabeth, CHU Henri Mondor [Créteil], and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Oncology, medicine.medical_specialty, medicine.medical_treatment, Follicular lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Lenalidomide, Lymphoma, Follicular, 030304 developmental biology, 0303 health sciences, Chemotherapy, Lymphoid Neoplasia, business.industry, Hematology, medicine.disease, Prognosis, Minimal residual disease, 3. Good health, Lymphoma, Regimen, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Rituximab, Bone marrow, business, medicine.drug
Abstract: Complete molecular response (CMR) after first-line immunochemotherapy reflects treatment efficacy and may predict prognosis in patients with follicular lymphoma (FL). RELEVANCE is the first phase 3 trial comparing the chemotherapy-free regimen lenalidomide/rituximab (R2) vs rituximab/chemotherapy (R-Chemo) in previously untreated FL patients (ClinicalTrials.gov identifier: NCT01650701). The objective of the minimal residual disease (MRD) analysis was to determine the ability of a chemotherapy-free regimen to induce CMR. Of 440 French patients participating in the Lymphoma Study Association (LYSA) RELEVANCE MRD study, all 222 patients with a BIOMED-2–detectable BCL2-JH translocation at diagnosis were analyzed. MRD was quantified by droplet digital polymerase chain reaction with a sensitivity ≤10−4. At week 24 (end of induction treatment), 98% and 78% of patients achieved CMR in peripheral blood (PB) and bone marrow (BM), respectively. Achievement of CMR (in PB and/or BM) had a significant impact on progression-free survival (PFS), with 3-year PFS of 84% and 55% for patients with CMR and detectable MRD, respectively (P = .015). CMR at week 24 was reached more frequently in the R2 arm (105/117; 90%) than in the R-Chemo arm (70/90; 77%) (P = .022). The poor prognostic value in terms of PFS for the persistence of molecular disease was observed irrespective of treatment arm (interaction test, P = .31). In agreement with the clinical results of the RELEVANCE trial, our results show that R2 immunomodulatory treatment in first-line FL can achieve high rates of CMR.
Published: 2020
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35. Computed Tomography-Aortography Versus Color-Duplex Ultrasound for Surveillance of Endovascular Abdominal Aortic Aneurysm Repair: A Prospective Multicenter Diagnostic-Accuracy Study (the ESSEA Trial)

Author: Elixène Jean-Baptiste, Patrick Feugier, Coralie Cruzel, Gabrielle Sarlon-Bartoli, Thierry Reix, Eric Steinmetz, Xavier Chaufour, Bertrand Chavent, Lucie Salomon du Mont, Meghann Ejargue, Blandine Maurel, Rafaelle Spear, Dominique Midy, Fabien Thaveau, Pascal Desgranges, Eugenio Rosset, Réda Hassen-Khodja, Pascale Bureau, Mireille Ravoux, Catherine Bozzetto, Marie-Antoinette Sevestre-Pietri, Béatrice Terriat, Claire Favier, Maryse Degeilh, Claire Le Hello, Jean-Pierre Favre, Simon Rinckenbach, Anca Loppinet, Yann Goueffic, Jérôme Connault, Yves Alimi, Pierre Barthélémy, Jean-Luc Magne, Christophe Seinturier, Marie-Luce Choukroun, Olivier Rouyer, Liliane Bitton, and Jean-Pierre Becquemin
Subjects: Male, medicine.medical_specialty, Aortography, Time Factors, Computed Tomography Angiography, medicine.medical_treatment, Computed tomography, Diagnostic accuracy, 030204 cardiovascular system & hematology, 030230 surgery, Likelihood ratios in diagnostic testing, Endovascular aneurysm repair, 03 medical and health sciences, Blood Vessel Prosthesis Implantation, 0302 clinical medicine, Postoperative Complications, Predictive Value of Tests, Color duplex ultrasound, Multidetector Computed Tomography, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Ultrasonography, Doppler, Color, Prospective cohort study, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, Endovascular Procedures, Reproducibility of Results, medicine.disease, Abdominal aortic aneurysm, Treatment Outcome, Retreatment, Female, Radiology, France, Cardiology and Cardiovascular Medicine, business, Aortic Aneurysm, Abdominal
Abstract: Background Color-duplex ultrasonography (DUS) could be an alternative to computed tomography-aortography (CTA) in the lifelong surveillance of patients after endovascular aneurysm repair (EVAR), but there is currently no level 1 evidence. The aim of this study was to assess the diagnostic accuracy of DUS as an alternative to CTA for the follow-up of post-EVAR patients. Methods Between December 16, 2010, and June 12, 2015, we conducted a prospective, blinded, diagnostic-accuracy study, in 15 French university hospitals where EVAR was commonly performed. Participants were followed up using both DUS and CTA in a mutually blinded setup until the end of the study or until any major aneurysm-related morphological abnormality requiring reintervention or an amendment to the follow-up policy was revealed by CTA. Database was locked on October 2, 2017. Our main outcome measures were sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratios of DUS against reference standard CTA. CIs are binomial 95% CI. Results This study recruited prospectively 659 post-EVAR patients of whom 539 (82%) were eligible for further analysis. Following the baseline inclusion visit, 940 additional follow-up visits were performed in the 539 patients. Major aneurysm-related morphological abnormalities were revealed by CTA in 103 patients (17.2/100 person-years [95% CI, 13.9–20.5]). DUS accurately identified 40 patients where a major aneurysm-related morphological abnormality was present (sensitivity, 39% [95% CI, 29–48]) and 403 of 436 patients with negative CTA (specificity, 92% [95% CI, 90–95]). The negative predictive value and positive predictive value of DUS were 92% (95% CI, 90–95) and 39% (95% CI, 27–50), respectively. The positive likelihood ratio was 4.87 (95% CI, 2.9–9.6). DUS sensitivity reached 73% (95% CI, 51–96) in patients requiring an effective reintervention. Conclusions DUS had an overall low sensitivity in the follow-up of patients after EVAR, but its performance improved meaningfully when the subset of patients requiring effective reinterventions was considered. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01230203.
Published: 2020

36. Analysis of a cohort of 279 patients with hairy-cell leukemia (HCL): 10 years of follow-up

Author: Xavier Troussard, Agnès Olivrie, Gandhi Damaj, Stephanie Noel, Jean-Claude Eisenmann, Olivier Hermine, Jérémie Riou, Sandrine Vaudaux, Patricia Validire-Charpy, Jean Gutnecht, Alain Devidas, Charlotte Petitdidier-Lionnet, Mohamed Touati, Stephanie Haiat, Vincent Levy, Fabienne Huysman, Eric Lippert, Aline Tanguy-Schmidt, Jehan Dupuis, Olivier Lambotte, Clara Mariette, Marouane Boubaya, Edouard Cornet, Pierre Feugier, Mathilde Hunault-Berger, Bertrand Joly, Stéphane Leprêtre, Jérôme Paillassa, Cécile Tomowiak, Kamel Ghomari, Willy Vaillant, Catherine Thieblemont, Mario Ojeda Uribe, Didier Decaudin, Bernard Drenou, Jean-Michel Karsenti, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor, Centre Hospitalier Sud Francilien [Corbeil-Essonnes] (CH Sud Francilien), Centre Hospitalier Universitaire [Grenoble] (CHU), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), CHU Limoges, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier d'Auch (CH Auch), Centre Hospitalier Intercommunal Fréjus - St Raphaël (CHI Fréjus - St Raphaël), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CH Beauvais, Hôpital Avicenne [AP-HP], Micro et Nanomédecines Translationnelles (MINT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), 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), Fédération Hospitalo-Universitaire 'Grand Ouest Against Leukemia' (FHU GOAL), 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: Adult, Male, medicine.medical_specialty, Disease-free survival, medicine.medical_treatment, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Chemotherapy, Hairy cell leukemia, Risk factor, Adverse effect, Cladribine, Aged, Aged, 80 and over, Hairy cell leukaemia, Leukemia, Hairy Cell, Adverse effects, business.industry, Incidence (epidemiology), Hematology, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, Leukemia, Treatment Outcome, Risk factors, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, business, Pentostatin, Follow-Up Studies, 030215 immunology, medicine.drug
Abstract: In total, 279 patients with hairy-cell leukemia (HCL) were analyzed, with a median follow-up of 10 years. Data were collected up to June 2018. We analyzed responses to treatment, relapses, survival, and the occurrence of second malignancies during follow-up. The median age was 59 years. In total, 208 patients (75%) were treated with purine analogs (PNAs), either cladribine (159) or pentosatin (49), as the first-line therapy. After a median follow-up of 127 months, the median overall survival was 27 years, and the median relapse-free survival (RFS) was 11 years. The cumulative 10-year relapse incidence was 39%. In patients receiving second-line therapy, the median RFS was 7 years. For the second-line therapy, using the same or another PNA was equivalent. We identified 68 second malignancies in 59 patients: 49 solid cancers and 19 hematological malignancies. The 10-year cumulative incidences of cancers, solid tumors, and hematological malignancies were 15%, 11%, and 5.0%, respectively, and the standardized incidence ratios were 2.22, 1.81, and 6.67, respectively. In multivariate analysis, PNA was not a risk factor for second malignancies. HCL patients have a good long-term prognosis. PNAs are the first-line treatment. HCL patients require long-term follow-up because of their relatively increased risk of second malignancies.
Published: 2020
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37. Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid

Author: Laura, Mechtouff, Monica, Sigovan, Philippe, Douek, Nicolas, Costes, Didier, Le Bars, Adeline, Mansuy, Julie, Haesebaert, Alexandre, Bani-Sadr, Jérémie, Tordo, Patrick, Feugier, Antoine, Millon, Stéphane, Luong, Salim, Si-Mohamed, Diane, Collet-Benzaquen, Emmanuelle, Canet-Soulas, Thomas, Bochaton, Claire, Crola Da Silva, Alexandre, Paccalet, David, Magne, Yves, Berthezene, and Norbert, Nighoghossian
Subjects: Positron-Emission Tomography, Calcinosis, Humans, Sodium Fluoride, Carotid Stenosis, Magnetic Resonance Imaging, Plaque, Atherosclerotic
Abstract: Previous studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) usingWe included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent
Published: 2020

38. A meta-analysis of outcomes of in-situ reconstruction after total or partial removal of infected abdominal aortic graft

Author: Michel Batt, Jocelyne Caillon, Fabrice Camou, Frédéric Laurent, Matthieu Revest, Christian Chidiac, Eric Senneville, Amandine Coffy, Jean Pierre Daures, Brigitte Calvet, and Patrick Feugier
Subjects: Male, medicine.medical_specialty, Prosthesis-Related Infections, 030204 cardiovascular system & hematology, Risk Assessment, Gastroenterology, Blood Vessel Prosthesis Implantation, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Cause of Death, Internal medicine, Humans, Medicine, In patient, Hospital Mortality, Device Removal, Male gender, Aged, Aged, 80 and over, business.industry, Mortality rate, Age Factors, General Medicine, Infected aortic graft, Middle Aged, Partial resection, Prognosis, Survival Analysis, Blood Vessel Prosthesis, 3. Good health, Increased risk, 030228 respiratory system, Meta-analysis, Female, Surgery, Cardiology and Cardiovascular Medicine, business, Statistical correlation, Aortic Aneurysm, Abdominal
Abstract: BACKGROUND: There is currently a lack of evidence for the relative effectiveness of partial resection (PR) and total resection (TR) before managing abdominal aortic graft infection (AGI). Most authorities agree that TR is mandatory for intracavitary AGI in patients with favorable conditions but there is an increasing number of patients with severe comorbidities for whom this approach is not suitable, resulting in a prohibitive mortality rate. The purpose of this study was to determine the most appropriate indication for TR or PR. METHODS: A meta-analysis was conducted on the rates of early/late mortality, amputations and reinfection. A meta-regression was performed with 8 variables: patient age, male prevalence, presence of virulent or nonvirulent organisms, urgency, omentoplasty and follow-up. RESULTS: Twenty-one studies and 1.052 patients were included. For TR and PR the rates of early mortality and reinfection were 16.8% and 10.5%, 11% and 27% respectively. For TR urgency and male gender were associated with increased rate of early mortality and male gender, PDF and virulent organisms were associated with increased risk of reinfection. For PR no statistical correlation was analyzable except for PDF with increased risk of reinfection. CONCLUSIONS: Early mortality rates are higher for TR and reinfection rates are higher for PR. For TR early mortality increases in urgent cases and it is suggested that alternative option must be discussed, reinfection decreases in the presence of nonvirulent organisms and TR seems optimal. For TR and PR reinfection increases in presence of PDF and alternative technique may be more appropriate.
Published: 2020
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39. Prognostic value of high-sensitivity measurable residual disease assessment after front-line chemoimmunotherapy in chronic lymphocytic leukemia

Author: Letestu, Rémi, Dahmani, Abdelmalek, Boubaya, Marouane, Baseggio, Lucile, Campos, Lydia, Chatelain, Bernard, Debliquis, Agathe, Drénou, Bernard, Jacob, Marie-Christine, Legac, Eric, Le Garff-Tavernier, Magali, Lhoumeau, Anne-Catherine, Quiney, Claire, Robillard, Nelly, Ticchioni, Michel, Aanei, Carmen, Katsahian, Sandrine, Delepine, Roselyne, Vaudaux, Sandrine, Rouillé, Valérie, Béné, Marie-Christine, Dartigeas, Caroline, Van Den Neste, Eric, Leprêtre, Stéphane, Feugier, Pierre, Cartron, Guillaume, Leblond, Véronique, Lévy, Vincent, Cymbalista, Florence, Cailleres, Sylvie, Damaj, Gandhi, Royer, Bruno, Gardembas, Martine, Dib, Mamoun, Truchan-Graczyk, Matgorzata, Hunault, Mathilde, Foussard, Charles, Corront, Bernadette, Parry, Anne, Orsini-Piocelle, Frédérique, Trouillier, Sébastien, Slama, Bohiane, Lepeu, Gérard, Zerazhi, Hacene, Boulat, Olivier, Azzedine, Ahmed, Araujo, Carla, Banos, Anne, Bauduer, Frédéric, Dutel, Jean-Luc, Ghomari, Kamel, Deconinck, Eric, Brion, Annie, Vuillier, Jacqueline, Saad, Alain, El Yamani, Abderrazak, Rodon, Philippe, Soubeyran, Pierre, Etienne, Gabriel, Dilhuydy, Marie-Sarah, Bouabdallah, Krimo, Leguay, Thibaut, Chouffi, Bachra, Pollet, Bertrand, Maakaroun, Abdallah, Guillerm, Gaëlle, Berthou, Christian, Cheron, Nathalie, ANDRÉ, Marc, Vilque, Jean Pierre, Fruchart, Christophe, Voillat, Laurent, Pica, Gian Matteo, Corm, Sélim, Micléa, Jean-Michel, Souleau, Bertrand, Molucon-Chabrot, Cécile, De Renzis, Benoit, Tournilhac, Olivier, Bay, Jacques-Olivier, Chaleteix, Carine, Guieze, Romain, Fleury, Joel, Precupanu, Cristina, Bouledroua, Selwa, Haiat, Stéphanie, Petitdidier, Charlotte, Dupuis, Jehan, Belhadj, Karim, Casasnovas, Olivier, Bastie, Jean-Noel, Ferrant, Emmanuelle, Gholam, Dany, Molina, Lysiane, Garban, Frédéric, Tiab, Mourad, Maisonneuve, Hervé, Villemagne, Bruno, Jacomy, Dominique, Besson, Caroline, Tertian, Gérard, Laribi, Kamel, Morel, Pierre, Cazin, Bruno, Moreau, Stéphane, Reminieras, Liliane, Rapp, Marie-José, Moreau, Philippe, Sebban, Catherine, Michallet, Anne-Sophie, Salles, Gilles, Broussais, Florence, Aurran-Schleinitz, Thérèse, Coso, Diane, Abarah, Wajed, Kulekci, Claire, Dorvaux, Véronique, Carassou, Philippe, Guibaud, Isabelle, Christian, Bernard, Graux, Carlos, Rossi, Jean-François, Quittet, Philippe, Dubois, Alain, Eisenmann, Jean-Claude, Morineau, Nadine, Mahé, Béatrice, Karsenti, Jean-Michel, Jourdan, Eric, Legouffe, Eric, Alexis-Vigier, Magda, Boulet, Jean-Michel, Aoudjhane, Malek, Thiéblemont, Catherine, Andreoli, Anna Lisa, Dreyfus, François, Choquet, Sylvain, Maloum, Karim, Merle-Béral, Hélène, Vekhoff, Anne, Decaudin, Didier, Brault, Philippe, Delarue, Richard, Janvier, Maud, Soussain, Carole, Vallantin, Xavier, Sanhes, Laurence, Dreyfus, Brigitte, Tomowiak, Cécile, Benramdane, Riad, Gonzalez, Hugo, Blaise-Brenna, Anne, Kolb, Brigitte, Delmer, Alain, Dauriac, Charles, Houot, Roch, Escoffre-Barbe, Martine, Lamy, Thierry, De Guibert, Sophie, Bernard, Marc, Grosbois, Bernard, Brehar, Oana, Morice, Patrick, Guyotat, Denis, Jaubert, Jérome, Portois, Christelle, Fornecker, Luc-Matthieu, Herbrecht, Raoul, Bilger, Karin, Ame, Shanti, Ysebaert, Loic, Godmer, Pascal, Jardel, Henry, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Saint-Etienne, CHU UCL Namur, Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), CHU Grenoble, Centre Hospitalier Régional d'Orléans (CHRO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Nice (CHU Nice), Hopital Saint-Louis [AP-HP] (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Montpellier (UM), UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, UCL - (MGD) Laboratoire de biologie clinique, UCL - (SLuc) Service d'hématologie, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: 0301 basic medicine, Male, Cancer Research, Neoplasm, Residual, MESH: Immunotherapy, Chronic lymphocytic leukemia, Gastroenterology, MESH: Clinical Trials, Phase III as Topic, 0302 clinical medicine, Bone Marrow, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, MESH: Leukemia, Lymphocytic, Chronic, B-Cell, MESH: Aged, education.field_of_study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, MESH: Follow-Up Studies, Prognosis, 3. Good health, Fludarabine, Survival Rate, Leukemia, MESH: Antineoplastic Combined Chemotherapy Protocols, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, MESH: Vidarabine, MESH: Bone Marrow, Female, MESH: Rituximab, Immunotherapy, Rituximab, MESH: Clinical Trials, Phase II as Topic, Vidarabine, medicine.drug, medicine.medical_specialty, Cyclophosphamide, MESH: Survival Rate, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Prognosis, 03 medical and health sciences, Clinical Trials, Phase II as Topic, Chemoimmunotherapy, Internal medicine, medicine, Humans, education, Survival rate, MESH: Neoplasm, Residual, Aged, Retrospective Studies, MESH: Humans, business.industry, MESH: Cyclophosphamide, MESH: Retrospective Studies, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, MESH: Male, body regions, 030104 developmental biology, Clinical Trials, Phase III as Topic, Bone marrow, business, MESH: Female, Follow-Up Studies
Abstract: International audience; Measurable residual disease (MRD) status is widely adopted in clinical trials in patients with chronic lymphocytic leukemia (CLL). Findings from FILO group trials (CLL2007FMP, CLL2007SA, CLL2010FMP) enabled investigation of the prognostic value of high-sensitivity (0.7 × 10-5) MRD assessment using flow cytometry, in blood (N = 401) and bone marrow (N = 339), after fludarabine, cyclophosphamide, and rituximab (FCR)-based chemoimmunotherapy in a homogeneous population with long follow-up (median 49.5 months). Addition of low-level positive MRD
Published: 2020
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40. Docosahexaenoic Acid (DHA) Bioavailability in Humans after Oral Intake of DHA-Containing Triacylglycerol or the Structured Phospholipid AceDoPC®

Author: Hachem, Mayssa, Nacir, Houda, Picq, Madeleine, Belkouch, Mounir, Bernoud-hubac, Nathalie, Windust, Anthony, Meiller, Laure, Sauvinet, Valerie, Feugier, Nathalie, Lambert-porcheron, Stephanie, Laville, Martine, Lagarde, Michel, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), ROSSI, Sabine, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)
Subjects: Male, Erythrocytes, Time Factors, Docosahexaenoic Acids, genetic structures, brain, gas chromatography combustion isotope ratio, Administration, Oral, Biological Availability, plasma phospholipids, lcsh:TX341-641, gas chromatography combustion isotope ratio mass spectrometry, Article, Gas Chromatography-Mass Spectrometry, Double-Blind Method, Humans, Triglycerides, Aged, Cross-Over Studies, food and beverages, Middle Aged, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Phosphatidylcholines, lipids (amino acids, peptides, and proteins), France, lcsh:Nutrition. Foods and food supply, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: AceDoPC® is a structured glycerophospholipid that targets the brain with docosahexaenoic acid (DHA) and is neuroprotective in the experimental ischemic stroke. AceDoPC® is a stabilized form of the physiological 2-DHA-LysoPC with an acetyl group at the sn1 position; preventing the migration of DHA from the sn2 to sn1 position. In this study we aimed to know the bioavailability of 13C-labeled DHA after oral intake of a single dose of 13C-AceDoPC®, in comparison with 13C-DHA in triglycerides (TAG), using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to assess the 13C enrichment of DHA-containing lipids. 13C-DHA enrichment in plasma phospholipids was significantly higher after intake of AceDoPC® compared with TAG-DHA, peaking after 24 h in both cases. In red cells, 13C-DHA enrichment in choline phospholipids was comparable from both sources of DHA, with a maximum after 72 h, whereas the 13C-DHA enrichment in ethanolamine phospholipids was higher from AceDoPC® compared to TAG-DHA, and continued to increase after 144 h. Overall, our study indicates that DHA from AceDoPC® is more efficient than from TAG-DHA for a sustained accumulation in red cell ethanolamine phospholipids, which has been associated with increased brain accretion.
Published: 2020
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41. Bariatric surgery affects obesity-related protein requirements

Author: Karem Slim, Yves Boirie, N. Lyon, M. Robert, M. Miolanne, Adeline Blot, B. Pereira, Christelle Guillet, E. Disse, N. Feugier, C. Louvet, N. Farigon, Martine Laville, P. Le Ruyet, A. Mishellany-Dutour, A. Masgrau, A. Caille, Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand, Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), LACTALIS RECHERCHE ET DEVELOPPEMENT (LACTALIS R&D), Groupe Lactalis, Service de Nutrition Clinique [CHU Clermont-Ferrand], and CHU Gabriel Montpied [Clermont-Ferrand]
Subjects: 0301 basic medicine, Nitrogen balance, Sleeve gastrectomy, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Protein requirements, Population, Gastric Bypass, 030209 endocrinology & metabolism, Context (language use), Urine, 03 medical and health sciences, 0302 clinical medicine, Recovery, Humans, Medicine, Longitudinal Studies, Prospective Studies, Temporal change, Obesity, education, Nutrition, Bariatric surgery, education.field_of_study, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Protein requirement, medicine.disease, Obesity, Morbid, Surgery, Cross-Sectional Studies, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Summary Context Following bariatric surgery, protein deficiency intakes are reported in morbidly obese patients, whereas post-bariatric protein requirements are not specifically defined with validated method in this population. Objective To assess average protein requirement (APR) in obese subjects, before, 3 months and 12 months after bariatric surgery using the validated method of nitrogen balance. Design and setting Prospective longitudinal study conducted in 21 morbidly obese patients (BMI 43.9 ± 1.4 kg/m2) before (M0), 3 months (M3) and 12 months (M12) after sleeve gastrectomy or Roux-en-Y gastric by-pass. An additional larger cross-sectional study was performed to validate APR before surgery in non-operated matched obese patients (n = 106). APR was evaluated at M0, M3, M12 by measuring 3 days dietary intakes together with losses of nitrogen in urine and stools. Main outcome measure APR was defined as the mean value of protein intake required to achieve balance nitrogen equilibrium. Results Before surgery, APR in morbidly obese patients was 0.76 [95%CI, 0.66–0.92] g/kg Body Weight (BW)/d in the experimental group, and 0.74 [0.70–0.80] g/kg BW/d in the validation group. APR was 0.62 [0.51–0.75] g/kg/d at M3 and 0.87 [0.75–0.98] g/kg/d at M12, with no difference between surgical procedures. Spontaneous protein intakes were respectively 0.80 ± 0.05, 0.43 ± 0.03 and 0.71 ± 0.04 g/kg BW/d respectively at M0, M3 and M12. Conclusion This study demonstrates a temporal change in protein requirement after bariatric surgery whatever the type of surgery. Spontaneous protein intakes following bariatric surgery does not cover protein requirements for most patients, suggesting that specific dietary protein recommandations have to be adapted in obese patients with bariatric surgery. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT01249326.
Published: 2020
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42. Assessment of fenestrated Anaconda stent graft design by numerical simulation: Results of a European prospective multicenter study

Author: Antoine Millon, Afshin Assadian, Sabrina Ben-Ahmed, Jürgen Falkensammer, Marine Bordet, Miriam Kliewer, Christian Muller, Nicolas Frisch, Jean Pierre Favre, Bertrand Chavent, Jan Willem Lardenoije, Patrick Feugier, Dominique Midy, Jean Noel Albertini, Michel M.P.J. Reijnen, Multi-Modality Medical Imaging, and TechMed Centre
Subjects: Models, Anatomic, medicine.medical_specialty, medicine.medical_treatment, Numerical simulation, Prosthesis Design, Anaconda, Blood Vessel Prosthesis Implantation, Postoperative Complications, Humans, Medicine, Computer Simulation, Aorta, Abdominal, Prospective Studies, Preoperative testing, biology, business.industry, Models, Cardiovascular, Stent, biology.organism_classification, n/a OA procedure, Surgery, Treatment Outcome, Multicenter study, Fenestrated endovascular aneurysm repair, Stents, Abdominal aneurysm, Cardiology and Cardiovascular Medicine, business, Fenestration, Aortic Aneurysm, Abdominal
Abstract: Objective A crucial step in designing fenestrated stent grafts for treatment of complex aortic abdominal aneurysms is the accurate positioning of the fenestrations. The deployment of a fenestrated stent graft prototype in a patient-specific rigid aortic model can be used for design verification in vitro, but is time and human resources consuming. Numerical simulation (NS) of fenestrated stent graft deployment using the finite element analysis has recently been developed; the aim of this study was to compare the accuracy of fenestration positioning by NS and in vitro. Methods All consecutive cases of complex aortic abdominal aneurysm treated with the Fenestrated Anaconda (Terumo Aortic) in six European centers were included in a prospective, observational study. To compare fenestration positioning, the distance from the center of the fenestration to the proximal end of the stent graft (L) and the angular distance from the 0° position (C) were measured and compared between in vitro testing (L1, C1) and NS (L2, C2). The primary hypothesis was that ΔL (|L2 – L1|) and ΔC (|C2 – C1|) would be 2.5 or less mm in more than 80% of the cases. The duration of both processes was also compared. Results Between May 2018 and January 2019, 50 patients with complex aortic abdominal aneurysms received a fenestrated stent graft with a total of 176 fenestrations. The ΔL and ΔC was 2.5 mm or less for 173 (98%) and 174 (99%) fenestrations, respectively. The NS process duration was significantly shorter than the in vitro (2.1 days [range, 1.0-5.2 days] vs 20.6 days [range, 9-82 days]; P Conclusions Positioning of fenestrations using NS is as accurate as in vitro and could significantly decrease delivery time of fenestrated stent grafts.
Published: 2022
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43. Serum albumin or body mass index: Which prognostic factor for survival in patients with acute myeloblastic leukaemia?

Author: Kossar Hosseini, Julien Broséus, Marc Muller, Gabrielle Roth-Guepin, Pierre Feugier, Christine Rotonda, Marie-Christine Béné, Aurore Perrot, Caroline Bonmati, Lauriane Filliatre-clement, Luciane Schirmer, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Génétique [CHRU Nancy], Plateforme d'Aide à la Recherche Clinique [CHRU Nancy] (PARC), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Service d’Hématologie Adulte [Hôpitaux de Brabois, CHU Nancy], and CHU de Nancy - Hôpitaux de Brabois
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Prognostic factor, Anthracycline, serum albumin, Serum albumin, Nutritional Status, body mass index, Kaplan-Meier Estimate, Overweight, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, In patient, ComputingMilieux_MISCELLANEOUS, Aged, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, 2. Zero hunger, biology, business.industry, Hematology, General Medicine, Middle Aged, Prognosis, medicine.disease, Survival Analysis, Obesity, 3. Good health, Leukemia, Myeloid, Acute, Oncology, 030220 oncology & carcinogenesis, biology.protein, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, acute myeloblastic leukaemia, medicine.symptom, Acute myeloblastic leukaemia, business, Body mass index, Biomarkers, 030215 immunology
Abstract: International audience; Obesity has been associated with an increased risk of developing acute myeloblastic leukaemia (AML). The outcome of AML patients could thus be dependent on their nutritional status that can be evaluated by the simple measurement of serum albumin (SA) and body mass index (BMI). These two parameters could have a value as prognostic factors to guide patients' management. We evaluated the association between SA levels, BMI, and survival, evaluated as overall survival (OS) and event-free survival. Furthermore, we investigated the association between BMI, SA, and other prognostic factors of interest in AML. This retrospective single-center study included 159 patients diagnosed with AML at Nancy Hospital between 2005 and 2013, treated with aracytine and anthracycline. Forty-four percent of patients presented with normal weight while 56% were obese/overweight. Serum albumin levels were
Published: 2018
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44. Effects on Mortality and Cardiovascular Events of Adherence to Guideline-Recommended Therapy 4 Years after Lower Extremity Arterial Revascularization

Author: Martina Thiney, Patrick Feugier, Antoine Millon, Nellie Della Schiava, René Ecochard, Anne Long, Patrick Lermusiaux, Département de chirurgie vasculaire, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Biostatistiques [Lyon], Hospices Civils de Lyon (HCL), Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Ultrasonore, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, Revascularization, Risk Assessment, Peripheral Arterial Disease, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Secondary Prevention, medicine, Humans, 030212 general & internal medicine, Practice Patterns, Physicians', ComputingMilieux_MISCELLANEOUS, Retrospective Studies, business.industry, Anticoagulants, Cardiovascular Agents, General Medicine, Guideline, Protective Factors, Vascular surgery, Confidence interval, Treatment Outcome, Lower Extremity, Practice Guidelines as Topic, Cohort, Arterial revascularization, Drug Therapy, Combination, Surgery, Observational study, Guideline Adherence, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Angiotensin II Type 1 Receptor Blockers, Vascular Surgical Procedures, Platelet Aggregation Inhibitors, Cohort study
Abstract: Background All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and HMG-CoA-reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the current risk of cardiovascular (CV) events and mortality and also to evaluate the effect of pharmacologic treatment on patient's survival, CV events, and additional vascular surgery in vascularized LE-PAD patients. This observational, cohort study analyzed prospectively collected data of 140 consecutive patients after hospitalization for LE-PAD revascularization in the vascular surgery department of our university hospital, between January 1 and June 30, 2013. Methods Data from guideline-recommended classes of medications (ACE, ARB, statins, and antiplatelet agents or anticoagulation) were collected at the time of discharge to hospitalization and at the end of the follow-up. Information about mortality, CV events, and additional vascular surgery was collected during follow-up. Results The mean follow-up of patients was 41 months. Mortality and CV events concerned 24% and 12% of the patients, respectively, and additional vascular surgery was performed in 33% of the patients. There was no difference in mortality and CV event rates according to pharmacologic treatment. Additional vascular surgery rate of LE-PAD patients with best medical treatment tended to be lower than without (incidence rate ratio = 0.5777; 95% confidence interval, 0.3101–1.06; P = 0.08). Best medical treatment was prescribed in 54% of patients at discharge of hospitalization. This proportion (54%) was statistically unchanged at the end of follow-up. Conclusions In this small cohort, we failed to show that best medical treatment decreased mortality or CV event rates, but it tended to be associated with decreased additional vascular surgery rate. Further studies taking into consideration the control of CV risk factors could be interesting to demonstrate better outcome from LE-PAD patients with best medical treatment compared with LE-PAD patients without. There is an urgent need for a more effective implementation of currently recommended medication and a continued search after more effective pharmacologic treatment options in LE-PAD.
Published: 2018
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45. Lenalidomide in combination with R-CHOP (R2-CHOP) as first-line treatment of patients with high tumour burden follicular lymphoma: a single-arm, open-label, phase 2 study

Author: Steven Le Gouill, Hervé Tilly, Reda Bouabdallah, Stéphanie Becker, Thierry Lamy, Jean Gabarre, Gilles Salles, Corinne Haioun, Fabrice Jardin, José Cabeçadas, Franck Morschhauser, Pierre Feugier, Nicolas Mounier, Olivier Casasnovas, Thierry Jo Molina, Olivier Tournilhac, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique, Médecine Nucléaire et Technologies Médicales (EA 1049), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Hôtel Dieu, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Instituto Português de Oncologia de Lisboa Francisco Gentil, Service de médecine nucléaire [Rouen], CRLCC Haute Normandie-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université de Rennes (UR)-Hôpital Pontchaillou
Subjects: Male, medicine.medical_specialty, Vincristine, Cyclophosphamide, [SDV]Life Sciences [q-bio], Follicular lymphoma, Phases of clinical research, Kaplan-Meier Estimate, CHOP, Antibodies, Monoclonal, Murine-Derived, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Lenalidomide, Lymphoma, Follicular, ComputingMilieux_MISCELLANEOUS, Aged, business.industry, Hematology, Middle Aged, medicine.disease, Thalidomide, Tumor Burden, 3. Good health, Doxorubicin, 030220 oncology & carcinogenesis, Prednisone, Female, Rituximab, business, 030215 immunology, medicine.drug
Abstract: Summary Background Immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is a standard front-line treatment for follicular lymphoma. The combination of lenalidomide and rituximab has shown high efficacy in relapsed or refractory and untreated follicular lymphoma. We aimed to evaluate the safety and activity of the combination of lenalidomide and R-CHOP (R2-CHOP) in previously untreated patients with high burden follicular lymphoma. Methods This single-arm, open-label, multicentre, phase 2 trial was done in 16 hospitals in France, all of which were Lymphoma Study Association (LYSA) sites. Eligible patients were aged 18–70 years and had previously untreated CD20-positive follicular lymphoma of grade 1, 2, or 3a; at least one high tumour burden criterion according to Groupe d'Etude des Lymphomes Folliculaires criteria; an Eastern Cooperative Oncology Group performance status score of 2 or less; and a minimum life expectancy of more than 3 months. Patients received induction therapy with six cycles of R2-CHOP every 3 weeks (one cycle involved standard R-CHOP on days 1–5, and 25 mg oral lenalidomide per day on days 1–14), followed by two rituximab infusions at 3-week intervals. The total treatment schedule was 24 weeks. Patients who achieved a complete or partial response to induction therapy received maintenance therapy consisting of one rituximab infusion every 8 weeks for 2 years. The primary outcome was the proportion of patients who achieved a complete response (complete response and complete response unconfirmed), according to International Workshop to Standardize Response Criteria, at the end of induction treatment. Safety was assessed in all patients who completed treatment. This trial is registered with ClinicalTrials.gov , number NCT01393756 , and is closed to accrual. Findings Between Dec 21, 2010, and Jan 25, 2012, 80 patients were enrolled, and 68 (85%) completed six cycles of R2-CHOP. At the end of the induction phase, 59 patients achieved a complete response (74%, 95% CI 63–83). 55 patients achieved a complete response at 30 months from enrolment (69%, 57–78). The most frequent adverse event was grade 4 neutropenia in 52 (65%) patients. The most frequent non-haematological side-effects included grade 1–2 sensory neuropathy in 28 (35%) patients and grade 1–2 transient rash in 27 (34%) patients. Four patients died during the study period; none of these deaths were judged to be related to treatment. Interpretations Lenalidomide in combination with R-CHOP had an acceptable safety profile and showed anti-cancer activity in patients with previously untreated high burden follicular lymphoma. A future comparative study showing evidence of a survival advantage would be necessary for this combination to be proposed as a treatment for follicular lymphoma. Funding French Ministry of Health, Celgene Corporation, and Amgen France.
Published: 2018
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46. Rituximab maintenance versus observation following abbreviated induction with chemoimmunotherapy in elderly patients with previously untreated chronic lymphocytic leukaemia (CLL 2007 SA): an open-label, randomised phase 3 study

Author: Sophie de Guibert, Thérèse Aurran-Schleinitz, Marie C. Béné, Hervé Maisonneuve, Anne-Sophie Michallet, Marie-Sarah Dilhuydy, Christian Berthou, Florence Cymbalista, Olivier Tournilhac, Stéphane Leprêtre, Eric Van Den Neste, Philippe Rodon, Kamel Laribi, Véronique Leblond, Florence Nguyen-Khac, Rémi Letestu, Pierre Feugier, Caroline Dartigeas, Jean-Pierre Vilque, Alain Delmer, Philippe Colombat, Julie Léger, Beatrice Mahe, Vincent Levy, Roselyne Delepine, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie, Centre hospitalier La Roche-Sur-Yon, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie clinique, Université de Rennes (UR)-Hôpital Pontchaillou, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique [Hôtel Dieu, Nantes], Hôtel-Dieu de Nantes, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Adaptateurs de signalisation en hématologie (ASIH), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Hématologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie, Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'Investigations Cliniques 9504, Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, medicine.medical_specialty, Population, Phases of clinical research, Neutropenia, 03 medical and health sciences, 0302 clinical medicine, Chemoimmunotherapy, Internal medicine, Clinical endpoint, Humans, Medicine, education, ComputingMilieux_MISCELLANEOUS, Aged, education.field_of_study, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Fludarabine, 030220 oncology & carcinogenesis, Female, Rituximab, Immunotherapy, business, Progressive disease, 030215 immunology, medicine.drug
Abstract: Summary Background Most patients with chronic lymphocytic leukaemia relapse after initial therapy combining chemotherapy with rituximab. We assessed the efficacy and safety of rituximab maintenance treatment versus observation for elderly patients in remission after front-line abbreviated induction by fludarabine, cyclophosphamide, and rituximab (FCR). Methods This randomised, open-label, multicentre phase 3 trial at 89 centres in France enrolled treatment-naive and fit patients aged 65 years or older with chronic lymphocytic leukaemia without del(17p). Eligible patients had an Eastern Cooperative Oncology Group performance status of 0–1 and adequate renal and hepatic function. Patients in response to complete induction treatment with four monthly courses of full-dose FCR with two interim rituximab doses on day 14 of cycles 1 and 2 (oral fludarabine [40 mg/m 2 per day] and oral cyclophosphamide [250 mg/m 2 per day] for the first 3 days of each cycle, rituximab at 375 mg/m 2 intravenously on day 0 of cycle 1 and subsequently at 500 mg/m 2 on day 14 of cycle 1, days 1 and 14 of cycle 2, and day 1 of cycles 3 and 4) were eligible for randomisation. Recovery from FCR toxicity and patient willingness to continue the trial were mandatory. We randomly assigned (1:1) patients to either receive intravenous rituximab (500 mg/m 2 ) every 8 weeks for up to 2 years or undergo observation, with a central computer-generated randomisation list using randomly permuted blocks of variable sizes. Randomisation was stratified by IGHV mutational status, the presence or absence of del(11q), and response level to induction treatment. The primary endpoint was progression-free survival, with the objective to assess the superiority of rituximab maintenance relative to observation. The final analysis was done in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug in the rituximab group and in all patients in the observation group. This trial is closed to accrual whilst continuing patient follow-up. The study is registered with ClinicalTrials.gov, number NCT00645606. Findings Between Dec 14, 2007, and Feb 18, 2014, 542 patients were enrolled, of whom 525 started FCR induction. Between June 10, 2008, and Aug 14, 2014, 409 (78%) patients were randomly assigned to rituximab maintenance (n=202) or observation (n=207). Four (2%) patients in the rituximab group did not receive the allocated treatment (progressive disease [n=1], adverse events [n=3]). After a median follow-up of 47·7 months (IQR 30·4–65·8), median progression-free survival in the rituximab group (59·3 months, 95% CI 49·6–not estimable) was improved compared with the observation group (49·0 months, 39·9–60·5; hazard ratio 0·55, 95% CI 0·40–0·75; p=0·0002). Neutropenia and grade 3–4 infections were more common with rituximab maintenance (105 [53%] of 198 patients vs 74 [36%] of 207 patients and 38 [19%] vs 21 [10%], respectively) during the study. The most common grade 3–4 infection was lower respiratory tract infection (24 [12%] vs eight [4%]). The incidence of second cancers, except basal cell carcinoma, was similar in both groups (29 [15%] vs 23 [11%]). Deaths were related to adverse events for 23 (11%) patients in the rituximab group and 16 (8%) in the observation group. Interpretation 2-year maintenance rituximab in selected elderly patients improves progression-free survival and shows an acceptable safety profile. Immunotherapy maintenance strategy is a relevant option in front-line treatment of chronic lymphocytic leukaemia, even in the age of targeted therapy. Funding French National Cancer Institute (INCa), Roche, Chugai.
Published: 2018
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47. Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma

Author: Morschhauser, Franck, Fowler, Nathan H, Feugier, Pierre, Bouabdallah, Reda, Tilly, Hervé, Palomba, M Lia, Fruchart, Christophe, Libby, Edward N, Casasnovas, Rene-Olivier, Flinn, Ian W, Haioun, Corinne, Maisonneuve, Hervé, Ysebaert, Loic, Bartlett, Nancy L, Bouabdallah, Kamal, Brice, Pauline, Ribrag, Vincent, Daguindau, Nicolas, Le Gouill, Steven, Pica, Gian M, Martin Garcia-Sancho, Alejandro, López-Guillermo, Armando, Larouche, Jean-François, Ando, Kiyoshi, Gomes da Silva, Maria, André, Marc, Zachée, Pierre, Sehn, Laurie H, Tobinai, Kensei, Cartron, Guillaume, Liu, David, Wang, Jianming, Xerri, Luc, Salles, Gilles A, Abdel-Samad N, Abdo-Matkiwsky M, Abraham J, Abrisqueta P, Anglaret B, Barnes JA, Benbrahim O, Bierman PJ, Bonnet C, Brault P, Bron D, Brooks BJ Jr, Byeff P, Casanova M, Cheung M, Choudhary Y, Comeau T, Cooper B, Couban S, Cox MC, Crump M, Deau Fischer B, Deconinck E, Deeren D, de la Cruz Vicente F, Delarue R, Del Campo R, Delmer A, Delwail V, Duggan PR, Eisenmann DJRM, El Yamani A, Eradat HA, Fabbro M, Farber C, Fisher DC, Fleischman RA, Fleck E, Fornecker LM, Foussard C, Gabarre J, Gaffar YA, Gallardo D, Ghazal H, Giagounidis A, Gill K, Glaisner S, Gonzalez H, Greenberg RH, Goubran Messiha H, Goy A, Gressin R, Gyan E, Hart LL, Hatake K, Hiddemann W, Hodossy B, Horkheimer I, Hoyer RJ, Huebel K, Ishikawa T, Izutsu K, Jardel H, Jhangiani HS, Johnson N, Joly B, Jourdan E, Kargar Samani K, Kato K, Kiguchi T, Kobayashi T, Kohser F, Koike M, Kouroukis C T, Laferriere N, Lamy de la Chapelle T, Landau DA, Lawler WE, Lemieux B, Levitan DA, Longree L, Lopez J, Mace J, Maerevoet M, Maigre M, Marjanovic Z, Michel J, Mounier C, Muntanola A, Ngirabacu MC, Nicolas-Virelizier E, Novelli S, Offner F, Palomera L, Pandit LH, Panwalkar A, Pierre P, Pignon JM, Pinto A, Plöger C, Pranger D, Quick DP, Reyes EA, Robin V, Robu D, Rodriguez Salazar MJ, Rosen PJ, Rosenbluth J, Sadot-Lebouvier S, Sangha R, Segota Z, Shapira I, Shtivelband M, Simon M, Soekler M, Soubeyran P, Taper J, Tereblo HR, Terol MJ, The AS, Ueda Y, van den Neste E, van Eygen K, van Hoof A, Vanstraelen G, Verner E, Warburton P, Yamamoto G, Yokoyama H, Zerazhi H, Zinzani PL., Morschhauser, Franck, Fowler, Nathan H, Feugier, Pierre, Bouabdallah, Reda, Tilly, Hervé, Palomba, M Lia, Fruchart, Christophe, Libby, Edward N, Casasnovas, Rene-Olivier, Flinn, Ian W, Haioun, Corinne, Maisonneuve, Hervé, Ysebaert, Loic, Bartlett, Nancy L, Bouabdallah, Kamal, Brice, Pauline, Ribrag, Vincent, Daguindau, Nicola, Le Gouill, Steven, Pica, Gian M, Martin Garcia-Sancho, Alejandro, López-Guillermo, Armando, Larouche, Jean-Françoi, Ando, Kiyoshi, Gomes da Silva, Maria, André, Marc, Zachée, Pierre, Sehn, Laurie H, Tobinai, Kensei, Cartron, Guillaume, Liu, David, Wang, Jianming, Xerri, Luc, Salles, Gilles A, Abdel-Samad N, Abdo-Matkiwsky M, Abraham J, Abrisqueta P, Anglaret B, Barnes JA, Benbrahim O, Bierman PJ, Bonnet C, Brault P, Bron D, Brooks BJ Jr, Byeff P, Casanova M, Cheung M, Choudhary Y, Comeau T, Cooper B, Couban S, Cox MC, Crump M, Deau Fischer B, Deconinck E, Deeren D, de la Cruz Vicente F, Delarue R, Del Campo R, Delmer A, Delwail V, Duggan PR, Eisenmann DJRM, El Yamani A, Eradat HA, Fabbro M, Farber C, Fisher DC, Fleischman RA, Fleck E, Fornecker LM, Foussard C, Gabarre J, Gaffar YA, Gallardo D, Ghazal H, Giagounidis A, Gill K, Glaisner S, Gonzalez H, Greenberg RH, Goubran Messiha H, Goy A, Gressin R, Gyan E, Hart LL, Hatake K, Hiddemann W, Hodossy B, Horkheimer I, Hoyer RJ, Huebel K, Ishikawa T, Izutsu K, Jardel H, Jhangiani HS, Johnson N, Joly B, Jourdan E, Kargar Samani K, Kato K, Kiguchi T, Kobayashi T, Kohser F, Koike M, Kouroukis C T, Laferriere N, Lamy de la Chapelle T, Landau DA, Lawler WE, Lemieux B, Levitan DA, Longree L, Lopez J, Mace J, Maerevoet M, Maigre M, Marjanovic Z, Michel J, Mounier C, Muntanola A, Ngirabacu MC, Nicolas-Virelizier E, Novelli S, Offner F, Palomera L, Pandit LH, Panwalkar A, Pierre P, Pignon JM, Pinto A, Plöger C, Pranger D, Quick DP, Reyes EA, Robin V, Robu D, Rodriguez Salazar MJ, Rosen PJ, Rosenbluth J, Sadot-Lebouvier S, Sangha R, Segota Z, Shapira I, Shtivelband M, Simon M, Soekler M, Soubeyran P, Taper J, Tereblo HR, Terol MJ, The AS, Ueda Y, van den Neste E, van Eygen K, van Hoof A, Vanstraelen G, Verner E, Warburton P, Yamamoto G, Yokoyama H, Zerazhi H, Zinzani PL., Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Lymphoma and Myeloma [Houston, TX, USA], The University of Texas M.D. Anderson Cancer Center [Houston], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d’Hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Unité des hémopathies lymphoïdes [CHU Henri Mondor], CHU Henri Mondor, Service d’Onco-Hématologie [La Roche sur Yon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), 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), Service d'hématologie [CHU Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service d'onco-hématologie [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], 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'Hématologie Clinique [Hôpital Hôtel Dieu, Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Hôtel Dieu, Service Hématologie [CH Métropole Savoie, Chambery], Centre Hospitalier Métropole Savoie [Chambéry], Département d'Hématologie [CHU de Montpellier], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Département d'Hématologie [CH Lyon-Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), RELEVANCE Trial Investigators : Abdel-Samad N, Abdo-Matkiwsky M, Abraham J, Abrisqueta P, Anglaret B, Barnes JA, Benbrahim O, Bierman PJ, Bonnet C, Brault P, Bron D, Brooks BJ Jr, Byeff P, Casanova M, Cheung M, Choudhary Y, Comeau T, Cooper B, Couban S, Cox MC, Crump M, Deau Fischer B, Deconinck E, Deeren D, de la Cruz Vicente F, Delarue R, Del Campo R, Delmer A, Delwail V, Duggan PR, Eisenmann DJRM, El Yamani A, Eradat HA, Fabbro M, Farber C, Fisher DC, Fleischman RA, Fleck E, Fornecker LM, Foussard C, Gabarre J, Gaffar YA, Gallardo D, Ghazal H, Giagounidis A, Gill K, Glaisner S, Gonzalez H, Greenberg RH, Goubran Messiha H, Goy A, Gressin R, Gyan E, Hart LL, Hatake K, Hiddemann W, Hodossy B, Horkheimer I, Hoyer RJ, Huebel K, Ishikawa T, Izutsu K, Jardel H, Jhangiani HS, Johnson N, Joly B, Jourdan E, Kargar Samani K, Kato K, Kiguchi T, Kobayashi T, Kohser F, Koike M, Kouroukis C T, Laferriere N, Lamy de la Chapelle T, Landau DA, Lawler WE, Lemieux B, Levitan DA, Longree L, Lopez J, Mace J, Maerevoet M, Maigre M, Marjanovic Z, Michel J, Mounier C, Muntanola A, Ngirabacu MC, Nicolas-Virelizier E, Novelli S, Offner F, Palomera L, Pandit LH, Panwalkar A, Pierre P, Pignon JM, Pinto A, Plöger C, Pranger D, Quick DP, Reyes EA, Robin V, Robu D, Rodriguez Salazar MJ, Rosen PJ, Rosenbluth J, Sadot-Lebouvier S, Sangha R, Segota Z, Shapira I, Shtivelband M, Simon M, Soekler M, Soubeyran P, Taper J, Tereblo HR, Terol MJ, The AS, Ueda Y, van den Neste E, van Eygen K, van Hoof A, Vanstraelen G, Verner E, Warburton P, Yamamoto G, Yokoyama H, Zerazhi H, Zinzani PL., Bernardo, Elizabeth, CHU Henri Mondor [Créteil], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Hospitalier Départemental Vendée, Service d'Hématologie [IUCT Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), 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: Adult, Male, medicine.medical_specialty, Neutropenia, Intention to Treat Analysi, Follicular lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, Skin Diseases, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Maintenance therapy, immune system diseases, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Survival rate, Lenalidomide, Lymphoma, Follicular, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocol, business.industry, Skin Disease, General Medicine, Middle Aged, medicine.disease, 3. Good health, Intention to Treat Analysis, Thalidomide, Survival Rate, Regimen, 030220 oncology & carcinogenesis, Rituximab, Female, business, Febrile neutropenia, 030215 immunology, medicine.drug, Human
Abstract: International audience; BACKGROUND:Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma; nevertheless, most patients will have a relapse. Combination immunotherapy with lenalidomide and rituximab is an immunomodulatory regimen that has shown promising activity in patients with indolent B-cell non-Hodgkin's lymphoma.METHODS:We conducted this multicenter, international, phase 3 superiority trial to evaluate rituximab plus lenalidomide, as compared with rituximab plus chemotherapy, in patients with previously untreated follicular lymphoma. Patients were randomly assigned to receive one of the two regimens, followed by maintenance monotherapy with rituximab. Treatment with rituximab plus lenalidomide consisted of 18 cycles of the two drugs, followed by rituximab maintenance therapy every 8 weeks for 12 cycles (six additional doses). Treatment with rituximab plus chemotherapy consisted of the investigator's choice of one of three rituximab-based regimens, followed by maintenance monotherapy with rituximab every 8 weeks for 12 cycles. The primary end points were complete response (confirmed or unconfirmed) at 120 weeks and progression-free survival.RESULTS:A total of 1030 patients were randomly assigned to receive rituximab plus lenalidomide (513 patients) or rituximab plus chemotherapy (517 patients). The rate of confirmed or unconfirmed complete response at 120 weeks was similar in the two groups: 48% (95% confidence interval [CI], 44 to 53) in the rituximab-lenalidomide group and 53% (95% CI, 49 to 57) in the rituximab-chemotherapy group (P=0.13). The interim 3-year rate of progression-free survival was 77% (95% CI, 72 to 80) and 78% (95% CI, 74 to 82), respectively. A higher percentage of patients in the rituximab-chemotherapy group had grade 3 or 4 neutropenia (32% vs. 50%) and febrile neutropenia of any grade (2% vs. 7%), and a higher percentage of patients in the rituximab-lenalidomide group had grade 3 or 4 cutaneous reactions (7% vs. 1%).CONCLUSIONS:Among patients with previously untreated follicular lymphoma, efficacy results were similar with rituximab plus lenalidomide and rituximab plus chemotherapy (with both regimens followed by rituximab maintenance therapy). The safety profile differed in the two groups. (Funded by Celgene; RELEVANCE ClinicalTrials.gov numbers, NCT01476787 and NCT01650701 , and EudraCT number, 2011-002792-42 .).
Published: 2018
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48. FDG-PET–driven consolidation strategy in diffuse large B-cell lymphoma: final results of a randomized phase 2 study

Author: Marc André, Alain Delmer, Catherine Thieblemont, Jean-François Emile, Nicolas Mounier, Richard Delarue, Stéphane Bardet, Franck Morschhauser, Loic Ysebaert, Jean-Philippe Jais, Emmanuel Bachy, Corinne Haioun, Alina Berriolo-Riedinger, Jean Gabarre, Hervé Tilly, Christophe Fruchart, Pierre Feugier, René-Olivier Casasnovas, Michel Meignan, and Sabine Tricot
Subjects: Adult, Male, medicine.medical_specialty, Vincristine, Endpoint Determination, Immunology, Salvage therapy, Phases of clinical research, Standardized uptake value, Biochemistry, Gastroenterology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Fluorodeoxyglucose F18, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, business.industry, Hematopoietic Stem Cell Transplantation, Reproducibility of Results, Cell Biology, Hematology, Middle Aged, medicine.disease, Surgery, Consolidation Chemotherapy, Treatment Outcome, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Vindesine, Female, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, 030215 immunology, medicine.drug
Abstract: Dose-dense induction and up-front consolidation with autologous stem cell transplantation (ASCT) remain controversial issues when treating patients with high-risk diffuse large B-cell lymphoma. GELA designed a randomized phase 2 trial evaluating the efficacy of either rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone (R-ACVBP) or rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP14) induction and a positron emission tomography (PET)-driven ASCT or standard immunochemotherapy (SIC) consolidation in age-adjusted international prognosis index 2 (aaIPI2)-aaIPI3 patients. PET was performed at baseline, after 2 (PET2) and 4 (PET4) induction cycles, and centrally assessed using international harmonization project (IHP) criteria. PET2-/PET4- patients were assigned SIC, PET2+/PET4- patients were assigned ASCT, and PET4+ patients were treated with the investigator's choice. The primary end-point was the 2007 international working group complete response (CR) rate after induction. Change in maximum standard uptake value (ΔSUVmax) after PET assessment was explored. Two hundred eleven patients were randomly assigned to R-ACVBP (n = 109) or R-CHOP14 (n = 102). PET4-/CR rates were 53%/47% with R-ACVBP and 41%/39% with R-CHOP14 (CR 95% confidence interval [CI], 38%-67% and 28%-54%, respectively; P = .076). Consolidation in the R-ACVBP and R-CHOP14 groups was SIC in 26% and 23% of patients and ASCT in 28% and 18% of patients, respectively. PET4 positivity was higher with R-CHOP14 vs R-ACVBP (54% vs 41%; P = .08), leading to more salvage therapy (37% vs 26%; P = .07) and lower event-free survival (EFS; 4-year EFS, 31% vs 43%; P 70% was associated with better outcome (4-year PFS, 84% vs 35%; 4-year OS, 91% vs 57%; P < .0001), whatever the consolidation. Superiority of R-ACVBP over R-CHOP14 was not established, as IHP criteria did not properly reflect disease control. ΔSUVmax may help better select patients needing an alternative to SIC, including ASCT.
Published: 2017
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49. Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1

Author: Veronique Leblond, Elise Chapiro, Claude Lesty, Madalina Uzunov, N Bougacha, Santos A. Susin, Florence Nguyen-Khac, M-N Brunelle-Navas, A Cosson, M Le Garff-Tavernier, Y Landesman, P. Feugier, Laurent Sutton, Véronique Morel, Damien Roos-Weil, Boris Keren, Hélène Merle-Béral, H-A Cung, Frederik Damm, L Herbi, Karim Maloum, Julie Lejeune, Sylvain Choquet, Stéphane Leprêtre, Jérôme Lambert, Caroline Algrin, Clementine Gabillaud, and Frederic Davi
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Chronic lymphocytic leukemia, Receptors, Cytoplasmic and Nuclear, Apoptosis, Drug resistance, Karyopherins, Biology, Fusion gene, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Gene, Regulation of gene expression, Hematology, Gene Expression Regulation, Leukemic, Triazoles, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Haematopoiesis, Leukemia, Hydrazines, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, Chromosomes, Human, Pair 2, 030220 oncology & carcinogenesis, Cancer research
Abstract: Gain in the short arm of chromosome 2 (2p+) induces gene overexpression and drug resistance in chronic lymphocytic leukemia: analysis of the central role of XPO1
Published: 2017
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50. What Is the Secondary Patency of Thrombosed Bypasses of the Lower Limbs Cleared by Fibrinolysis In Situ?

Author: Myriam Ammi, Patrick Feugier, Jean Picquet, Tchala Kassegne, Samir Henni, Nellie Della Schiava, and Université d'Angers (UA)
Subjects: Male, medicine.medical_specialty, Time Factors, Secondary patency, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Risk Assessment, Amputation, Surgical, 030218 nuclear medicine & medical imaging, Blood Vessel Prosthesis Implantation, Peripheral Arterial Disease, 03 medical and health sciences, 0302 clinical medicine, Fibrinolytic Agents, Recurrence, Risk Factors, Fibrinolysis, medicine, Humans, Thrombolytic Therapy, Survival rate, Vascular Patency, Aged, Retrospective Studies, Urokinase, business.industry, Graft Occlusion, Vascular, Thrombosis, Retrospective cohort study, General Medicine, Middle Aged, Limb Salvage, medicine.disease, 3. Good health, Surgery, Treatment Outcome, Lower Extremity, Amputation, Adjunctive treatment, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract: In case of acute thrombosis, lower limb bypasses can, in certain cases, be cleared by local intra-arterial fibrinolysis (LIF). The aim of this study is to evaluate the secondary patency of thrombosed bypasses after fibrinolysis.This retrospective study includes all patients hospitalized for thrombosed bypasses of the lower limbs that were treated with in situ fibrinolysis using urokinase, between 2004 and 2013, in 2 French university hospital centers. Fibrinolysis was indicated in case of recent thrombosis (3 weeks) provoking acute limb ischemia without sensory-motor deficit and in the absence of general contraindications. The secondary patency of the grafts was defined as the time after fibrinolysis without a new thrombotic event.There were 207 patients, hospitalized for recent thrombosis of 244 bypasses. The LIF was efficient in 74% of the cases (n = 180). Secondary patency of these bypasses was 54.2% and 32.4% overall, 68.3% and 50.3% for the suprainguinal bypasses, and 48.3% and 21.5% for the infrainguinal bypasses at 1 and 5 years, respectively. There is a significant difference (P = 0.002) regarding the permeability of the suprainguinal and infrainguinal bypasses. The survival rate was 75% (±6.4%) at 5 years and the limb salvage rate was 89% (±3.3%), 78.2% (±5.1%), and 75% (±5.8%) at 1, 3, and 5 years, respectively. The only independent factor influencing the secondary patency of infrainguinal bypasses that was significant in a multivariate analysis was the infragenicular localization of the distal anastomosis (P = 0.023).LIF is an effective approach that often allows the identification of the underlying cause, permitting elective adjunctive treatment of the underlying cause. Although LIF is at least as effective as its therapeutic alternatives described in the literature, the secondary patency of the bypasses remains modest and encourages close monitoring, particularly in patients with an infragenicular bypass.
Published: 2019
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