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1. Blinatumomab after R-CHOP bridging therapy for patients with Richter transformation: a phase 2 multicentre trial

Author

Guièze, Romain, Ysebaert, Loïc, Roos-Weil, Damien, Fornecker, Luc-Mathieu, Ferrant, Emmanuelle, Molina, Lysiane, Aurran, Thérèse, Clavert, Aline, de Guibert, Sophie, Michallet, Anne-Sophie, Saad, Alain, Drénou, Bernard, Quittet, Philippe, Hivert, Bénédicte, Laribi, Kamel, Gay, Julie, Quinquenel, Anne, Broseus, Julien, Rouille, Valérie, Schwartz, David, Magnin, Benoit, Lazarian, Grégory, Véronèse, Lauren, de Antonio, Marie, Laurent, Camille, Tournilhac, Olivier, Pereira, Bruno, and Feugier, Pierre

Published
2024
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2. Final results on effectiveness and safety of Ibrutinib in patients with chronic lymphocytic leukemia from the non-interventional FIRE study

Author

Dartigeas, Caroline, Quinquenel, Anne, Ysebaert, Loïc, Dilhuydy, Marie-Sarah, Anglaret, Bruno, Slama, Borhane, Le Du, Katell, Tardy, Stéphanie, Tchernonog, Emmanuelle, Orfeuvre, Hubert, Voillat, Laurent, Guidez, Stéphanie, Malfuson, Jean-Valère, Dupuis, Sandrine, Deslandes, Marine, Feugier, Pierre, and Leblond, Véronique

Published
2024
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3. Blinatumomab after R-CHOP bridging therapy for patients with Richter transformation: a phase 2 multicentre trial

Author

Romain Guièze, Loïc Ysebaert, Damien Roos-Weil, Luc-Mathieu Fornecker, Emmanuelle Ferrant, Lysiane Molina, Thérèse Aurran, Aline Clavert, Sophie de Guibert, Anne-Sophie Michallet, Alain Saad, Bernard Drénou, Philippe Quittet, Bénédicte Hivert, Kamel Laribi, Julie Gay, Anne Quinquenel, Julien Broseus, Valérie Rouille, David Schwartz, Benoit Magnin, Grégory Lazarian, Lauren Véronèse, Marie de Antonio, Camille Laurent, Olivier Tournilhac, Bruno Pereira, and Pierre Feugier

Subjects
Science
Abstract

Abstract Richter transformation (RT) is an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia. Here we investigated the anti-CD3/anti-CD19 T-cell-engager blinatumomab after R-CHOP (i.e. rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with untreated RT of diffuse large B-cell lymphoma histology (NCT03931642). In this multicentre phase 2 study, patients without complete response (CR) after two cycles of R-CHOP were eligible to receive an 8-week blinatumomab induction via continuous vein infusion with stepwise dosing until 112 μg/day. The primary endpoint was the CR rate after blinatumomab induction and secondary endpoint included safety, response duration, progression-free and overall survival. Thirty-nine patients started the first cycle of R-CHOP, 25 of whom received blinatumomab. After blinatumomab induction, five (20%) patients achieved CR, four (16%) achieved partial response, and six (24%) were stable. Considering the entire strategy, the overall response rate in the full-analysis-set was 46% (n = 18), with CR in 14 (36%) patients. The most common treatment-emergent adverse events of all grades in the blinatumomab-safety-set included fever (36%), anaemia (24%), and lymphopaenia (24%). Cytokine release syndrome (grade 1/2) was observed in 16% and neurotoxicity in 20% of patients. Blinatumomab demonstrated encouraging anti-tumour activity (the trial met its primary endpoint) and acceptable toxicity in patients with RT.

Published
2024
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4. Faire vivre et grandir une communauté de chefs de service : acte 2 en hématologie

Author

Houot, Roch, Calmettes, Claire, Park, Sophie, Pascal, Laurent, Peffault de Latour, Regis, Pigneux, Arnaud, Quinquenel, Anne, Raffoux, Emmanuel, Thieblemont, Catherine, Touati, Mohamed, Trebouet, Adrien, Vaida, Ioana, Wémeau, Mathieu, Bastie, Jean-Noël, Bay, Jacques-Olivier, Cluzeau, Thomas, Cornillon, Jérôme, Damaj, Ghandi, Deconinck, Eric, Feugier, Pierre, Fornecker, Luc-Matthieu, Gay, Julie, Hermine, Olivier, Hospital, Marie Anne, Hunault, Mathilde, Jaccard, Arnaud, Jardin, Fabrice, Le Calloch, Ronan, Legros, Laurence, Leleu, Xavier, Lemonnier, François, Malfuson, Jean-Valere, Morel, Pierre, Ochmann, Marlene, Orsini-Piocelle, Frédérique, and Gyan, Emmanuel

Published
2024
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5. Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis

Author

Broséus, Julien, Hergalant, Sébastien, Vogt, Julia, Tausch, Eugen, Kreuz, Markus, Mottok, Anja, Schneider, Christof, Dartigeas, Caroline, Roos-Weil, Damien, Quinquenel, Anne, Moulin, Charline, Ott, German, Blanchet, Odile, Tomowiak, Cécile, Lazarian, Grégory, Rouyer, Pierre, Chteinberg, Emil, Bernhart, Stephan H., Tournilhac, Olivier, Gauchotte, Guillaume, Lomazzi, Sandra, Chapiro, Elise, Nguyen-Khac, Florence, Chery, Céline, Davi, Frédéric, Hunault, Mathilde, Houlgatte, Rémi, Rosenwald, Andreas, Delmer, Alain, Meyre, David, Béné, Marie-Christine, Thieblemont, Catherine, Lichter, Peter, Ammerpohl, Ole, Guéant, Jean-Louis, Guièze, Romain, Martin-Subero, José Ignacio, Cymbalista, Florence, Feugier, Pierre, Siebert, Reiner, and Stilgenbauer, Stephan

Published
2023
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8. Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis

Author

Julien Broséus, Sébastien Hergalant, Julia Vogt, Eugen Tausch, Markus Kreuz, Anja Mottok, Christof Schneider, Caroline Dartigeas, Damien Roos-Weil, Anne Quinquenel, Charline Moulin, German Ott, Odile Blanchet, Cécile Tomowiak, Grégory Lazarian, Pierre Rouyer, Emil Chteinberg, Stephan H. Bernhart, Olivier Tournilhac, Guillaume Gauchotte, Sandra Lomazzi, Elise Chapiro, Florence Nguyen-Khac, Céline Chery, Frédéric Davi, Mathilde Hunault, Rémi Houlgatte, Andreas Rosenwald, Alain Delmer, David Meyre, Marie-Christine Béné, Catherine Thieblemont, Peter Lichter, Ole Ammerpohl, Jean-Louis Guéant, ICGC MMML-Seq Consortium, Romain Guièze, José Ignacio Martin-Subero, Florence Cymbalista, Pierre Feugier, Reiner Siebert, and Stephan Stilgenbauer

Subjects
Science
Abstract

Richter syndrome (RS) is the transformation of chronic lymphocytic leukaemia (CLL) into aggressive lymphoma, in most cases diffuse large B-cell lymphoma (DLBCL). Here, the authors characterize the DNA methylation and transcriptomic profiles of RS samples, find a clonally-related CLL epigenetic imprint, and develop classifiers for “RS-type” de novo DLBCLs.

Published
2023
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10. Primary oral mucosa-associated lymphoid tissue (MALT) lymphoma in patient with monoclonale gammopathy: a rare case report

Author

Hilal Hafian, Hubert Schvartz, Martine Patey, and Anne Quinquenel

Subjects
Mucosa-associated lymphoid tissue (MALT), Monoclonal gammopathy, Lymphoma, Oral mucosa, Light chain, Haemopathy, Dentistry, RK1-715
Abstract

Abstract Background Monoclonal gammopathy is a biological reality encountered in approximately 1% of the general population. In the absence of clinical and biological signs, it is considered of undetermined significance; however, it can be a biological signature of a monoclonal lymphocytic or plasma-cell proliferation. Their localisation to the oral mucosa remains rare and difficult to diagnose, particularly in indolent forms that escape imaging techniques. Case presentation Here, we report the case of a 73-year-old woman with a history of IgM kappa gammopathy followed for 13 years. The patient did not have a chronic infection or an autoimmune disease, and all the biological investigations and radiological explorations were unremarkable during this period. The discovery of a submucosal nodule in the cheek led to the diagnosis of MALT lymphoma and regression of half of the IgM kappa level after resection. The review of the literature shows the dominance of clinical signs (i.e., a mass or swelling) in the diagnosis of primary MALT lymphomas of the oral cavity after surgical resection. Conclusions Our case illustrates the role of examination of the oral cavity in the context of a monoclonal gammopathy. The absence of clinical and radiological evidence in favor of lymphoplasmacytic proliferation, does not exclude a primary indolent MALT lymphoma of the oral mucosa.

Published
2021
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11. Corneal in vivo confocal microscopy to detect belantamab mafodotin-induced ocular toxicity early and adjust the dose accordingly: a case report

Author

Kevin Marquant, Anne Quinquenel, Carl Arndt, and Alexandre Denoyer

Subjects
Multiple myeloma, Antibody–drug conjugate, Ocular toxicity, Microcystic keratopathy, In vivo confocal microscopy, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background New targeted antibody–drug conjugates (ADCs) against multiple myeloma are known to induce adverse effects that may lead to treatment discontinuation. Preclinical studies reported early severe ocular damage related to the use of belantamab mafodotin (belamaf), including ocular surface inflammation, severe dry eye, and a specific toxicity to the cornea, namely microcystic keratopathy. While belamaf-induced ocular changes have not been prospectively studied, a better understanding of mechanisms involved as well as kinetics may aid in anticipating dose adjustment rather than stopping the treatment once clinical ocular damage is too severe. Case presentation A 61-year-old woman scheduled for belamaf as a fifth-line treatment against multiple myeloma was prospectively included. Clinical examinations were performed before and every 3 weeks afterward, together with in vivo confocal microscopy (IVCM) of the cornea. Visual acuity, symptoms, slit-lamp examination, and ultrastructural changes of the cornea were recorded according to the received dose of belamaf. More precisely, kinetics, shape, density, and location of the toxic corneal lesions have been followed and analyzed using IVCM. Also, specific lesions at the sub-basal nerve plexus layer were detected and characterized for the first time. This advanced approach allowed a better understanding of the belamaf-induced toxicity, further balancing the dose to maintain good vision and eye health while continuing the treatment. Conclusions Systematic ultrastructural analysis and follow-up of the corneal state during ADCs treatment for multiple myeloma may open new avenues in the therapeutic approach. Early preclinical detection of ocular damage may accurately contribute to finding the correct dose for each patient and not stopping the treatment due to severe ocular adverse effects.

Published
2021
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12. Pretreatment CT Texture Parameters as Predictive Biomarkers of Progression-Free Survival in Follicular Lymphoma Treated with Immunochemotherapy and Rituximab Maintenance

Author

Carole Durot, Eric Durot, Sébastien Mulé, David Morland, François Godard, Anne Quinquenel, Alain Delmer, Philippe Soyer, and Christine Hoeffel

Subjects
follicular lymphoma, positron emission tomography, tomography, X-ray computed, Medicine (General), R5-920
Abstract

The purpose of this study was to determine whether texture analysis features present on pretreatment unenhanced computed tomography (CT) images, derived from 18F-fluorodeoxyglucose positron emission/computed tomography (18-FDG PET/CT), can predict progression-free survival (PFS), progression-free survival at 24 months (PFS 24), time to next treatment (TTNT), and overall survival in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance. Seventy-two patients with follicular lymphoma were retrospectively included. Texture analysis was performed on unenhanced CT images extracted from 18-FDG PET/CT examinations that were obtained within one month before treatment. Skewness at a fine texture scale (SSF = 2) was an independent predictor of PFS (hazard ratio = 3.72 (95% CI: 1.15, 12.11), p = 0.028), PFS 24 (hazard ratio = 13.38; 95% CI: 1.29, 138.13; p = 0.029), and TTNT (hazard ratio = 5.11; 95% CI: 1.18, 22.13; p = 0.029). Skewness values above −0.015 at SSF = 2 were significantly associated with lower PFS, PFS 24, and TTNT. Kurtosis without filtration was an independent predictor of PFS (SSF = 0; HR = 1.22 (95% CI: 1.04, 1.44), p = 0.013), and TTNT (SSF = 0; hazard ratio = 1.23; 95% CI: 1.04, 1.46; p = 0.013). This study shows that pretreatment unenhanced CT texture analysis-derived tumor skewness and kurtosis may be used as predictive biomarkers of PFS and TTNT in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance.

Published
2023
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13. Efficacy of eculizumab in refractory life‐threatening warm autoimmune hemolytic anemia associated with chronic myelomonocytic leukemia

Author

Anne‐Cécile Gauchy, Maxime Hentzien, Alain Wynckel, Victoire de Marcellus, Cyrielle Rodier, Alain Delmer, and Anne Quinquenel

Subjects
chronic myelomonocytic leukemia, eculizumab, warm autoimmune hemolytic anemia, Medicine, Medicine (General), R5-920
Abstract

Abstract Eculizumab may be considered as an emergency therapeutic option in refractory life‐threatening warm autoimmune hemolytic anemia especially if direct antiglobulin test is positive for both IgG and C3d and after failure of all conventional treatments.

Published
2020
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14. Final results on effectiveness and safety of Ibrutinib in patients with chronic lymphocytic leukemia from the non-interventional FIRE study

Author

DARTIGEAS, Caroline, primary, QUINQUENEL, Anne, additional, YSEBAERT, Loïc, additional, DILHUYDY, Marie-Sarah, additional, ANGLARET, Bruno, additional, SLAMA, Borhane, additional, DU, Katell LE, additional, TARDY, Stéphanie, additional, TCHERNONOG, Emmanuelle, additional, ORFEUVRE, Hubert, additional, VOILLAT, Laurent, additional, GUIDEZ, Stéphanie, additional, MALFUSON, Jean-Valère, additional, DUPUIS, Sandrine, additional, DESLANDES, Marine, additional, FEUGIER, Pierre, additional, and LEBLOND, Véronique, additional

Published
2024
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17. Stabilization of β-catenin upon B-cell receptor signaling promotes NF-kB target genes transcription in mantle cell lymphoma

Author

Lazarian, Gregory, Friedrich, Chloe, Quinquenel, Anne, Tran, Julie, Ouriemmi, Souhail, Dondi, Elisabetta, Martin, Antoine, Mihoub, Imane, Chiron, David, Bellanger, Céline, Fleury, Carole, Gélébart, Pascal, McCormack, Emmet, Ledoux, Dominique, Thieblemont, Catherine, Marzec, Jacek, Gribben, John G., Cymbalista, Florence, Varin-Blank, Nadine, Gardano, Laura, and Baran-Marszak, Fanny

Published
2020
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18. The CARMEN-France registry of adult patients with immune thrombocytopenia and autoimmune hemolytic anemia in France

Author

Ackermann, Felix, Adoue, Daniel, Alexandra, Jean-François, Alric, Laurent, Andre, Baptiste, Arista, Sophie, Astudillo, Leonardo, Audia, Sylvain, Badet, Françoise, Balardy, Laurent, Berezne, Alice, Bonmati, Caroline, Bonnet, Delphine, Borel, Cécile, Bories, Eva, Bouillet, Laurence, Boutboul, David, Branco, Benoit, Brechemier, Delphine, Briantais, Antoine, Brun, Natacha, Carreiro, Miguel, Castel, Brice, Cathebras, Pascal, Catros, Florian, Caubet, Olivier, Caudrelier, Léo, Chaminade, Axel, Chauveheid, Marie-Paul, Cheze, Stéphane, Chezel, Julie, Clement, Mélissa, Comont, Thibault, Corvilain, Emilie, Cougoul, Pierre, Courtault, Carine, Crickx, Etienne, Damian, Louise, De Almeida, Sébastien, de Sainte Marie, Benjamin, Decker, Paul, Deibener-Kaminsky, Joëlle, Delavigne, Karen, Delbrel, Xavier, Denis, Guillaume, Deshayes, Samuel, Dingremont, Claire, Dion, Jérémie, Dossier, Antoine, Duffau, Pierre, Dumont, Anne, Dupont, Romain, Durand, Jean-Marc, Ebbo, Mikael, Eshagh, Deborah, Fadlallah, Jehane, Farhat, Meryem, Faucher, Benoit, Faurie, Pierre, Faurie, Thomas, Fieschi, Claire, Galicier, Lionel, Garric, Marie, Gaudin, Clément, Gauthier, Martin, Gerfaud-Valentin, Mathieu, Ghrenassia, Etienne, Giraud, Jean-Thomas, Gobert, Delphine, Godel-Labouret, Aurélie, Goulenok, Tiphaine, Gourguechon, Clément, Goursaud, Laure, Graveleau, Julie, Grobost, Vincent, Guilpain, Philippe, Hadj-Khelifa, Sondess, Harle, Jean-Robert, Hebraud, Benjamin, Hennique, Hélène, Hot, Arnaud, Issaka, Ismaël, Jaussaud, Roland, Jean, Estelle, Jeandel, Pierre-Yves, Khatibi, Sarah, Kouchit, Yanis, Laribi, Kamel, Lazareth, Anne, Lechtman, Sarah, Leguenno, Guillaume, Lemeu, Mélanie, Lemonnier, Margaux, Leplay, Lorraine, Leveneur, Yann, Levraut, Michael, Lifermann, François, Limal, Nicolas, Lioger, Bertrand, Lobbes, Hervé, Loustau, Valentine, Machelart, Irène, Madaule, Serge, Mahevas, Matthieu, Maigne, Gwenola, Malphettes, Marion, Maquet, Julien, Martin-Blondel, Guillaume, Martis, Nihal, Merckx, Antoine, Michaud, Martin, Mohamed, Shirine, Moignet-Autrel, Aline, Montes, Lydia, Moulinet, Thomas, Mourguet, Morgane, Nuccio, Fanny, Orvain, Corentin, Pan Petesch, Brigitte, Papo, Thomas, Paricaud, Kim, Pastissier, Andréa, Perard, Laurent, Piel-Julian, Marie-Léa, Pinede, Laurent, Pontille, Fabien, Prudhomme, Laurent, Pugnet, Grégory, Quinquenel, Anne, Rauzy, Odile, Recher, Christian, Remy, Véronique, Reynaud, Quitterie, Rieu, Virginie, Rigal, Florence, Rispal, Patrick, Rivet, Valérian, Robbins, Ailsa, Rohmer, Julien, Roumier, Mathilde, Ruivard, Marc, Saada, Noemie, Sacre, Karim, Sailler, Laurent, Saint-Lezer, Arnaud, Saunier, Aurélie, Sauvetre, Gaetan, Schleinitz, Nicolas, Seguier, Julie, Sire, Stéphane, Soubrier, Caroline, Swiader, Laure, Tavitian, Suzanne, Terriou, Louis, Thomazeau, Josephine, Toledano, Albanie, Urbanski, Geoffrey, Veit, Véronique, Versini, Mathilde, Viallard, Jean-François, Walter, Ondine, Moulis, Guillaume, Michel, Marc, Bonnotte, Bernard, and Godeau, Bertrand

Published
2024
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19. 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, and Julien Broséus

Subjects
Richter syndrome, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, genomics, microenvironment, immune checkpoint, Immunologic diseases. Allergy, RC581-607
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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20. Diagnosis and Treatment of Chronic Lymphocytic Leukemia: Recommendations of the French CLL Study Group (FILO)

Author

Anne Quinquenel, Thérèse Aurran-Schleinitz, Aline Clavert, Florence Cymbalista, Caroline Dartigeas, Frédéric Davi, Sophie de Guibert, Alain Delmer, Marie-Sarah Dilhuydy, Pierre Feugier, Luc-Matthieu Fornecker, David Ghez, Romain Guieze, Kamel Laribi, Véronique Leblond, Stéphane Leprêtre, Rémi Letestu, Vincent Lévy, Florence Nguyen-Khac, Anne-Sophie Michallet, Cécile Tomowiak, Olivier Tournilhac, Loïc Ysebaert, Xavier Troussard, and on the behalf of the FILO-LLC Group

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract. As a result of significant recent developments, the management of patients with chronic lymphocytic leukemia (CLL) is changing, and new therapeutic options will continue to emerge in the near future. The recommendations of the French Innovative Leukemia Organization (FILO-CLL) group presented here are intended to provide practical recommendations for physicians taking care of CLL patients, taking into account the availability of both biological tests and therapies in daily practice in France at the time of publication. This text details the documented information and guidelines on diagnosis, indications for treatment, infectious complications and therapeutic strategies in frontline and relapsed CLL as well as in particular conditions such as autoimmune cytopenia or Richter syndrome.

Published
2020
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25. Pretreatment CT Texture Parameters as Predictive Biomarkers of Progression-Free Survival in Follicular Lymphoma Treated with Immunochemotherapy and Rituximab Maintenance

Author

Hoeffel, Carole Durot, Eric Durot, Sébastien Mulé, David Morland, François Godard, Anne Quinquenel, Alain Delmer, Philippe Soyer, and Christine

Subjects
follicular lymphoma, positron emission tomography, tomography, X-ray computed
Abstract

The purpose of this study was to determine whether texture analysis features present on pretreatment unenhanced computed tomography (CT) images, derived from 18F-fluorodeoxyglucose positron emission/computed tomography (18-FDG PET/CT), can predict progression-free survival (PFS), progression-free survival at 24 months (PFS 24), time to next treatment (TTNT), and overall survival in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance. Seventy-two patients with follicular lymphoma were retrospectively included. Texture analysis was performed on unenhanced CT images extracted from 18-FDG PET/CT examinations that were obtained within one month before treatment. Skewness at a fine texture scale (SSF = 2) was an independent predictor of PFS (hazard ratio = 3.72 (95% CI: 1.15, 12.11), p = 0.028), PFS 24 (hazard ratio = 13.38; 95% CI: 1.29, 138.13; p = 0.029), and TTNT (hazard ratio = 5.11; 95% CI: 1.18, 22.13; p = 0.029). Skewness values above −0.015 at SSF = 2 were significantly associated with lower PFS, PFS 24, and TTNT. Kurtosis without filtration was an independent predictor of PFS (SSF = 0; HR = 1.22 (95% CI: 1.04, 1.44), p = 0.013), and TTNT (SSF = 0; hazard ratio = 1.23; 95% CI: 1.04, 1.46; p = 0.013). This study shows that pretreatment unenhanced CT texture analysis-derived tumor skewness and kurtosis may be used as predictive biomarkers of PFS and TTNT in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance.

Published
2023
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26. Preliminary Results of the Filo Phase 2 Trial for Untreated Fit Patients with Intermediate Risk Chronic Lymphocytic Leukemia Comparing Ibrutinib Plus Venetoclax (IV) Versus FCR: Results of the Month 15 MRD Evaluation

Author

Anne Quinquenel, Rémi Letestu, Magali Le Garff-Tavernier, Fabien Subtil, Therese Aurran-Schleinitz, Kamel Laribi, Florence Cymbalista, Vincent Levy, Laurence Simon, Damien Roos-Weil, Véronique Leblond, Marie-Sarah Dilhuydy, Caroline Dartigeas, Cecile Tomowiak, Romain Guieze, Olivier Tournilhac, Emmanuelle Ferrant, Sophie de Guibert, Pierre Feugier, Fatiha Merabet, Stephane Lepretre, Philippe Carassou, Julie Gay, Bénédicte Hivert, Luc Mathieu Fornecker, Jehan Dupuis, Lysiane Molina, Bruno Villemagne, Guillaume Cartron, Bernard Drenou, Béatrice Mahé, Omar Benbrahim, Xavier Cahu, Christelle Portois, Loic Ysebaert, Florence Nguyen Khac, Valérie Rouille, Alain Delmer, and Anne-Sophie Michallet

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

27. Plasmocytome solitaire osseux : caractéristiques et facteurs associés au risque d’évolution vers le myélome multiple, sur une cohorte de 31 patients suivis au CHU de Reims entre janvier 2000 et juin 2022

Author

Vellutini, L., primary, Charlot, I., additional, Geoffroy, M., additional, Chopin, C., additional, Dorilleau, C., additional, Bolko, L., additional, Hittinger, A., additional, Fabre, J., additional, Papathanassiou, D., additional, Quinquenel, A., additional, Kanagaratnam, L., additional, and Salmon, J.H., additional

Published
2022
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29. Primary oral mucosa-associated lymphoid tissue (MALT) lymphoma in patient with monoclonale gammopathy: a rare case report

Author

Martine Patey, Anne Quinquenel, Hubert Schvartz, and Hilal Hafian

Subjects
Pathology, medicine.medical_specialty, Lymphoma, Lymphoid Tissue, Population, Case Report, Context (language use), Head and neck, Gammopathy, Mucosa-associated lymphoid tissue (MALT), medicine, Humans, Oral mucosa, education, General Dentistry, Haemopathy, Aged, Autoimmune disease, Mouth, education.field_of_study, Light chain, business.industry, Monoclonal gammopathy, Mouth Mucosa, MALT lymphoma, RK1-715, Lymphoma, B-Cell, Marginal Zone, medicine.disease, medicine.anatomical_structure, Dentistry, Monoclonal, Female, Persistent Infection, Extra nodal, business
Abstract

Background Monoclonal gammopathy is a biological reality encountered in approximately 1% of the general population. In the absence of clinical and biological signs, it is considered of undetermined significance; however, it can be a biological signature of a monoclonal lymphocytic or plasma-cell proliferation. Their localisation to the oral mucosa remains rare and difficult to diagnose, particularly in indolent forms that escape imaging techniques. Case presentation Here, we report the case of a 73-year-old woman with a history of IgM kappa gammopathy followed for 13 years. The patient did not have a chronic infection or an autoimmune disease, and all the biological investigations and radiological explorations were unremarkable during this period. The discovery of a submucosal nodule in the cheek led to the diagnosis of MALT lymphoma and regression of half of the IgM kappa level after resection. The review of the literature shows the dominance of clinical signs (i.e., a mass or swelling) in the diagnosis of primary MALT lymphomas of the oral cavity after surgical resection. Conclusions Our case illustrates the role of examination of the oral cavity in the context of a monoclonal gammopathy. The absence of clinical and radiological evidence in favor of lymphoplasmacytic proliferation, does not exclude a primary indolent MALT lymphoma of the oral mucosa.

Published
2021

30. Corneal in vivo confocal microscopy to detect belantamab mafodotin-induced ocular toxicity early and adjust the dose accordingly: a case report

Author

Anne Quinquenel, Kevin Marquant, Carl Arndt, Alexandre Denoyer, Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie Médicale et Moléculaire - EA 4684 (CardioVir), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), and Gestionnaire, HAL Sorbonne Université 5

Subjects
In vivo confocal microscopy, Cancer Research, medicine.medical_specialty, Antibody-drug conjugate, Visual acuity, genetic structures, Case Report, Antibodies, Monoclonal, Humanized, Microcystic keratopathy, Corneal Diseases, Cornea, 03 medical and health sciences, 0302 clinical medicine, Ocular toxicity, Multiple myeloma, Internal medicine, Ophthalmology, Humans, Medicine, Diseases of the blood and blood-forming organs, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Adverse effect, Molecular Biology, RC254-282, Microscopy, Confocal, Hematology, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, medicine.disease, eye diseases, 3. Good health, Discontinuation, medicine.anatomical_structure, Oncology, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030220 oncology & carcinogenesis, Toxicity, 030221 ophthalmology & optometry, Female, sense organs, medicine.symptom, RC633-647.5, business, Antibody–drug conjugate
Abstract

Background New targeted antibody–drug conjugates (ADCs) against multiple myeloma are known to induce adverse effects that may lead to treatment discontinuation. Preclinical studies reported early severe ocular damage related to the use of belantamab mafodotin (belamaf), including ocular surface inflammation, severe dry eye, and a specific toxicity to the cornea, namely microcystic keratopathy. While belamaf-induced ocular changes have not been prospectively studied, a better understanding of mechanisms involved as well as kinetics may aid in anticipating dose adjustment rather than stopping the treatment once clinical ocular damage is too severe. Case presentation A 61-year-old woman scheduled for belamaf as a fifth-line treatment against multiple myeloma was prospectively included. Clinical examinations were performed before and every 3 weeks afterward, together with in vivo confocal microscopy (IVCM) of the cornea. Visual acuity, symptoms, slit-lamp examination, and ultrastructural changes of the cornea were recorded according to the received dose of belamaf. More precisely, kinetics, shape, density, and location of the toxic corneal lesions have been followed and analyzed using IVCM. Also, specific lesions at the sub-basal nerve plexus layer were detected and characterized for the first time. This advanced approach allowed a better understanding of the belamaf-induced toxicity, further balancing the dose to maintain good vision and eye health while continuing the treatment. Conclusions Systematic ultrastructural analysis and follow-up of the corneal state during ADCs treatment for multiple myeloma may open new avenues in the therapeutic approach. Early preclinical detection of ocular damage may accurately contribute to finding the correct dose for each patient and not stopping the treatment due to severe ocular adverse effects.

Published
2021

31. Myeloid malignancies with translocation t(4;12)(q11‐13;p13): molecular landscape, clonal hierarchy and clinical outcomes

Author

François Lifermann, Jean-Alain Martignoles, Anne Quinquenel, Vincent Parinet, Christine Lefebvre, Pierre Hirsch, Mélanie Martin, Sabine Defasque, Florence Nguyen-Khac, Matthieu Decamp, Laurence Simon, Dominique Penther, Nadia Ali-Ammar, Elise Chapiro, Odile Maarek, Chrystele Bilhou-Nabera, Baptiste Gaillard, Agathe Maillon, Jean-Baptiste Micol, Marine Baron, Nathalie Auger, Stéphanie Struski, Damien Roos-Weil, Sylvie Tondeur, Marie-Joelle Mozziconacci, Audrey Bidet, 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), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], 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 de Paris (UP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Robert Debré, 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), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratoire CERBA [Saint Ouen l'Aumône], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Génétique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Hospitalier de Dax, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Génétique (Biologie pathologie), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Service d'immunologie et hématologies biologiques [CHU Saint-Antoine], 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), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), 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), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), HAL-SU, Gestionnaire, École Pratique des Hautes Études (EPHE), 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
Male, Oncology, Myeloid, [SDV]Life Sciences [q-bio], Chromosomal translocation, Translocation, Genetic, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, 12), In Situ Hybridization, Fluorescence, Aged, 80 and over, CHIC2, Middle Aged, Immunohistochemistry, 3. Good health, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, medicine.anatomical_structure, RUNX1, 030220 oncology & carcinogenesis, Cytogenetic Analysis, Cohort, Molecular Medicine, Female, Original Article, Chromosomes, Human, Pair 4, medicine.medical_specialty, IDH1, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, Genetic Predisposition to Disease, acute myeloid leukaemia, Genetic Association Studies, Aged, Chromosome Aberrations, Chromosomes, Human, Pair 12, Myeloproliferative Disorders, business.industry, Myelodysplastic syndromes, Original Articles, ETV6, Cell Biology, medicine.disease, myelodysplastic syndrome, t(4, chemistry, Fusion transcript, Myelodysplastic Syndromes, prognosis, business, 030215 immunology
Abstract

International audience; Translocation t(4;12)(q11-13;p13) is a recurrent but very rare chromosomal aberration in acute myeloid leukaemia (AML) resulting in the non-constant expression of a CHIC2/ETV6 fusion transcript. We report clinico-biological features, molecular characteristics and outcomes of 21 cases of t(4;12) including 19 AML and two myelodysplastic syndromes (MDS). Median age at the time of t(4;12) was 78 years (range, 56–88). Multilineage dysplasia was described in 10 of 19 (53%) AML cases and CD7 and/or CD56 expression in 90%. FISH analyses identified ETV6 and CHIC2 region rearrangements in respectively 18 of 18 and 15 of 17 studied cases. The t(4;12) was the sole cytogenetic abnormality in 48% of cases. The most frequent associated mutated genes were ASXL1 (n = 8/16, 50%), IDH1/2 (n = 7/16, 44%), SRSF2 (n = 5/16, 31%) and RUNX1 (n = 4/16, 25%). Interestingly, concurrent FISH and molecular analyses showed that t(4;12) can be, but not always, a founding oncogenic event. Median OS was 7.8 months for the entire cohort. In the 16 of 21 patients (76%) who received antitumoral treatment, overall response and first complete remission rates were 37% and 31%, respectively. Median progression-free survival in responders was 13.7 months. Finally, t(4;12) cases harboured many characteristics of AML with myelodysplasia-related changes (multilineage dysplasia, MDS-related cytogenetic abnormalities, frequent ASXL1 mutations) and a poor prognosis.

Published
2021

33. Corneal iatrogenicity of Belantamab Mafodotin (GSK2857916), Clinical and Morphological In Vivo Confocal Microscopy follow-up of a case series

Author

David Mostrel, Kevin Marquant, Anne Quinquenel, Carl Arndt, and Alexandre Denoyer

Abstract

Objective : To highlight the potential importance of confocal microscopy (IVCM) in the follow-up of patients with refractory multiple myeloma treated with Belantamab Mafodotin. Methods : A retrospective case series of 8 patients with refractory multiple myeloma treated with belantamab mafodotin was reported. Ophthalmologic follow-up of these patients every 3 weeks before each new infusion included systematic corneal examination with IVCM. A complementary analysis of the morphological data collected in IVCM was performed to evaluate the density, the average size and the circularity of the lesions observed. Results : In case 1, the iatrogenic damage was maximal at the 6th week of follow-up with an important damage of Bowman's layer, leading to the suspension of the treatment. After resumption of treatment at a reduced dosage, the morphological damage to the cornea was reduced. In case 2, the onset of iatrogenic damage related to the treatment was observed but the follow-up was interrupted early because of therapeutic escape of the disease. In case 3, a prolonged follow-up could be performed showing a good tolerance to the treatment. In case 4, a decrease in visual acuity was observed at the 6th week of follow-up in connection with the treatment-related toxicity well observed in IVCM. Follow-up was then interrupted due to therapeutic escape of the disease. In cases 5 and 6, a significant decrease in visual acuity was observed at the 6th week in relation to iatrogenic morphological anomalies of the central cornea. The resumption of treatment at a reduced dosage was accompanied by an improved tolerance. In cases 7 and 8, the patients did not develop specific damage. Conclusion : Our study showed the interest of corneal morphological follow-up in IVCM in patients treated with belantamab mafodotin in order to detect early signs of corneal iatrogenicity and to guide the management accordingly, before the suspension of treatment.

Published
2022

34. Preliminary Results of the Filo Phase 2 Trial for Untreated Fit Patients with Intermediate Risk Chronic Lymphocytic Leukemia Comparing Ibrutinib Plus Venetoclax (IV) Versus FCR: Results of the Month 15 MRD Evaluation

Author

Quinquenel, Anne, primary, Letestu, Rémi, additional, Le Garff-Tavernier, Magali, additional, Subtil, Fabien, additional, Aurran-Schleinitz, Therese, additional, Laribi, Kamel, additional, Cymbalista, Florence, additional, Levy, Vincent, additional, Simon, Laurence, additional, Roos-Weil, Damien, additional, Leblond, Véronique, additional, Dilhuydy, Marie-Sarah, additional, Dartigeas, Caroline, additional, Tomowiak, Cecile, additional, Guieze, Romain, additional, Tournilhac, Olivier, additional, Ferrant, Emmanuelle, additional, de Guibert, Sophie, additional, Feugier, Pierre, additional, Merabet, Fatiha, additional, Lepretre, Stephane, additional, Carassou, Philippe, additional, Gay, Julie, additional, Hivert, Bénédicte, additional, Fornecker, Luc Mathieu, additional, Dupuis, Jehan, additional, Molina, Lysiane, additional, Villemagne, Bruno, additional, Cartron, Guillaume, additional, Drenou, Bernard, additional, Mahé, Béatrice, additional, Benbrahim, Omar, additional, Cahu, Xavier, additional, Portois, Christelle, additional, Ysebaert, Loic, additional, Nguyen Khac, Florence, additional, Rouille, Valérie, additional, Delmer, Alain, additional, and Michallet, Anne-Sophie, additional

Published
2022
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37. Feasibility and Impact of Adapted Physical Activity (APA) in Cancer Outpatients Beginning Medical Anti-Tumoral Treatment: The UMA-CHAPA Study

Author

Amélie Lemoine, Marine Perrier, Camille Mazza, Anne Quinquenel, Mathilde Brasseur, Alain Delmer, Hervé Vallerand, Maxime Dewolf, Eric Bertin, Coralie Barbe, Damien Botsen, and Olivier Bouché

Subjects
Cancer Research, Oncology, adapted physical activity, feasibility, muscle strength, anxiety, cancer patients
Abstract

Adapted physical activity (APA) improves quality of life and cancer outcomes. The aim of this study was to assess the feasibility of an APA program in outpatients beginning medical anticancer treatment. The secondary objective was to assess the impact of APA on fatigue, anxiety, depression, and handgrip strength (HGS). This prospective study was conducted between January and July 2017. Among 226 patients beginning treatment in the unit for a digestive, lung, hematological, or dermatological cancer, 163 were included. Adherence to the APA program was defined as more than or equal to one one-hour session per week for 3 months. The first evaluation was conducted at 3 months (M3), and the second evaluation at 6 months (M6). A total of 163 patients were included (mean age 62.5 ± 14.3); 139 (85.3%) agreed to follow the APA program. At M3, 106 of them were evaluated, of which 86 (81.1%) declared that they had followed the program. Improvement in anxiety was observed at M3 (−1.0 ± 3.2; p = 0.002) but there was no significant change in fatigue or depression. HGS decreased significantly (−1.2 ± 5.5; p = 0.04). The APA program was feasible in cancer outpatients beginning medical anticancer treatment. APA should be part of standard support care.

Published
2022

40. Feasibility and Impact of Adapted Physical Activity (APA) in Cancer Outpatients Beginning Medical Anti-Tumoral Treatment: The UMA-CHAPA Study

Author

Lemoine, Amélie, primary, Perrier, Marine, additional, Mazza, Camille, additional, Quinquenel, Anne, additional, Brasseur, Mathilde, additional, Delmer, Alain, additional, Vallerand, Hervé, additional, Dewolf, Maxime, additional, Bertin, Eric, additional, Barbe, Coralie, additional, Botsen, Damien, additional, and Bouché, Olivier, additional

Published
2022
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41. 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

42. Impact of MYD88 L265P mutation status on histological transformation of Waldenström Macroglobulinemia

Author

Gita Thanarajasingam, Anne Quinquenel, Anne J. Novak, Angela Dispenzieri, Nelson Leung, Wilson I. Gonsalves, Rebecca L. King, Prashant Kapoor, Rong He, Jose C. Villasboas, Ronald S. Go, Carrie A. Thompson, Yi Lin, Robert A. Kyle, Taxiarchis Kourelis, Thomas E. Witzig, Jennifer Le-Rademacher, Shaji Kumar, Gabriela Perez Burbano, S. Vincent Rajkumar, Jithma P. Abeykoon, Rahma Warsame, Eli Muchtar, Patrick B. Johnston, Francis K. Buadi, Patricia T. Greipp, Pascale Cornillet-Lefebvre, Ivana N. Micallef, Eric Durot, Alain Delmer, David J. Inwards, Thomas M. Habermann, Martha Q. Lacy, N. Nora Bennani, Saurabh Zanwar, David Dingli, Grzegorz S. Nowakowski, Morie A. Gertz, and Stephen M. Ansell

Subjects
medicine.medical_specialty, Multivariate analysis, business.industry, Waldenstrom macroglobulinemia, Hematology, Odds ratio, medicine.disease, Gastroenterology, Lymphoma, Internal medicine, Cohort, medicine, Missense mutation, business, Complication, Survival rate
Abstract

Histological transformation in Waldenstrom macroglobulinemia (WM) is an uncommon complication, with limited data, particularly regarding the impact of MYD88 L265P mutation on transformation. We examined risk factors and outcomes associated with transformation in WM, highlighting the role of MYD88 L265P mutation. Patients with WM seen at Mayo Clinic, Rochester, USA and University Hospital of Reims, France, between 01/01/1996 and December 31, 2017 were included; 50 (4.3%) of 1147 patients transformed to a high-grade lymphoma, with median time-to-transformation of 4.5 (range 0-21) years in the transformed cohort. The MYD88 L265P mutation status was known in 435/1147 (38%) patients (406 with non-transformed WM and 29 patients in transformed cohort). On multivariate analysis, MYD88 WT status alone was an independent predictor of transformation (odds ratio, 7[95%CI: 2.1-23]; P = .003). Additionally, the MYD88 WT status was independently associated with shorter time-to-transformation (HR 7.9 [95%CI: 2.3-27; P = .001]), with a 5-year transformation rate of 16% for MYD88 WT vs 2.8% with MYD88 L265P mutated patients. Patients with transformation demonstrated a significant increase in risk of death compared to patients who did not transform (HR 5.075; 95%CI: 3.8-6.8; P < .001). In conclusion, the MYD88 WT status is an independent predictor of transformation and associated with a shorter time-to-transformation. Additionally, transformation conferred an inferior overall survival in patients with WM.

Published
2019

46. Identification and analysis of clinical phenotypes in COPD patients: PALOMB Cohort

Author

Claire Bon, Frederic Pilard, Remi Veillon, Chantal Raherison-Semjen, Emmanuel Monge, Maeva Zysman, Laura Petrov, Elodie Blanchard, Mohammed Staali, Christophe Roy, Jean Moinard, Frédéric Le Guillou, Emilie Berteaud, Jean Michel Dupis, Mathieu Molimard, Mohammed Aliati, Yannick Daoudi, Marc Sapene, Cécilia Nocent-Ejnaini, Xavier Demant, Leo Grassion, Esther Iglesias, L. Falque, J. Casteigt, A. Bernady, El-hassane Ouaalaya, Julie Macey, Marie Line Quinquenel, Laurent Nguyen, Annaig Ozier, Marielle Sabatini, and A. Prudhomme

Subjects
COPD, medicine.medical_specialty, Copd patients, business.industry, Mortality rate, Disease cluster, medicine.disease, Phenotype, respiratory tract diseases, Chronic cough, Diabetes mellitus, Internal medicine, Cohort, medicine, medicine.symptom, business
Abstract

In recent years, several researchers have attempted to identify COPD phenotypes using different cluster analysis. This study aimed to determine the most optimal cluster analysis (supervised vs unsupervised) to robustly identify clinical phenotypes. 2,968 COPD patients have been included from January 2014 until February 2020. General information (age, BMI, smoking, comorbidities), lung function, exacerbations and symptoms were collected. After 5 years of follow-up, vital status was recorded. A hierarchical classification on the principal components (HCPC) was performed, followed by two unsupervised classification algorithms: k-means and PAM (Partition Around Medoids). Robustness was defined according to three different indices of validation (Connectivity, Dunn and silhouette). The mean age was 70 years, 63.7% of males, current smokers: 38.7%, mean FEV1: 61.3% predicted, ≥2 exacerbations: 43.6%, mMRC dyspnea grade≥2: 56.3%, chronic cough: 58%. The 5-year mortality rate was 11.3%. Based on our hypothesis, four phenotypes were described, using the PAM method. The phenotype A (24.2%) consisted of elderly patients with severe airflow limitation, low symptoms, cardiovascular comorbidities, diabetes and a higher mortality. The phenotype B (23.9%) contained more female patients, young patients with moderate airflow limitation and a high rate of current smokers. The phenotype C (25.5%) contained patients with very severe airflow limitation, more symptoms and low BMI. The Phenotype D (26.2%) was composed of patients with mild airflow limitation and low dyspnoea. These results showed the superiority of PAM classification compared with two other algorithms (k-means and HCPC) in terms of the robustness.

Published
2021

48. Th17/Treg ratio in human graft-versus-host disease

Author

Ratajczak, Philippe, Janin, Anne, Peffault de Latour, Regis, Leboeuf, Christophe, Desveaux, Allison, Keyvanfar, Keyvan, Robin, Marie, Clave, Emmanuel, Douay, Corine, Quinquenel, Anne, Pichereau, Claire, Bertheau, Philippe, Mary, Jean Yves, and Socié, Gérard

Published
2010
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49. Génération automatique de courbes de niveaux dans les zones de plateaux karstiques

Author

Touya, Guillaume, Boulze, Hugo, Schleich, Anouk, Quinquenel, Hervé, Laboratoire sciences et technologies de l'information géographique (LaSTIG), Ecole des Ingénieurs de la Ville de Paris (EIVP)-École nationale des sciences géographiques (ENSG), Institut National de l'Information Géographique et Forestière [IGN] (IGN)-Université Gustave Eiffel-Institut National de l'Information Géographique et Forestière [IGN] (IGN)-Université Gustave Eiffel, Centre de recherche nantais Architectures Urbanités (CRENAU ), Ambiances, Architectures, Urbanités (AAU), École Centrale de Nantes (ECN)-École nationale supérieure d'architecture de Nantes (ENSA Nantes)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-École nationale supérieure d'architecture de Grenoble (ENSAG ), Université Grenoble Alpes (UGA)-Université Grenoble Alpes (UGA)-École Centrale de Nantes (ECN)-École nationale supérieure d'architecture de Nantes (ENSA Nantes)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-École nationale supérieure d'architecture de Grenoble (ENSAG ), Université Grenoble Alpes (UGA)-Université Grenoble Alpes (UGA), École nationale des sciences géographiques (ENSG), Institut National de l'Information Géographique et Forestière [IGN] (IGN)-Université Gustave Eiffel, and Institut National de l'Information Géographique et Forestière [IGN] (IGN)

Subjects
topographic map, digital terrain model, map generalization, [INFO]Computer Science [cs], contour line
Abstract

National audience; Contour lines are a key features of topographic maps as they make the comprehension of terrain more easy. But they are no longer drawn by cartographers, they are mostly automatically derived from digital terrain models. Despite real progress in this automated derivation, some specific terrain landscapes remain incorrectly depicted with such techniques, and this is the case for karstic plateaus full of sinkholes. This paper proposes a specific automated method to derive better contour lines in plateaus, particularly around sinkholes. The process first detects karstic plateaus with many sinkholes, as well as the individual sinkholes. Then, the MNT is smoothed to better reflect the terrain in the plateau and in its surroundings. As a third step, the contour lines around sinkholes are enhanced to draw legible round features that better reflect the real terrain. The process was implemented in a QGIS plugin and tested on a small area with a karstic plateau in the Jura mountain in France, and the cartographers of IGN, the French national mapping agency assessed the results as a great improvement compared to the generic automated process to derive contour lines.; Les courbes de niveau sont l'un des éléments clés des cartes topographiques, car elles facilitent la compréhension du terrain. Mais elles ne sont plus dessinées par des cartographes, elles sont la plupart du temps automatiquement dérivées de modèles numériques de terrain (MNT). Malgré de réels progrès dans cette dérivation automatisée, certains paysages spécifiques restent mal représentés avec de telles techniques, et c'est le cas des plateaux karstiques contenant un grand nombre de dolines (petites dépressions du relief). Cet article propose une méthode automatisée pour obtenir de meilleures courbes de niveau dans ces plateaux, notamment autour des dolines. Le processus détecte d'abord les plateaux karstiques comportant de nombreuses dolines, ainsi que les dolines individuellement. Ensuite, le MNT est lissé afin de mieux refléter le relief du plateau et de ses environs. Dans une troisième étape, les courbes de niveau autour des dolines sont améliorées pour dessiner des éléments ronds lisibles qui reflètent mieux le terrain réel. Le processus a été mis en oeuvre dans un plugin QGIS et testé sur une petite zone avec un plateau karstique dans le Jura, en France, et les cartographes de l'IGN, ont évalué les résultats comme une grande amélioration par rapport au processus automatisé générique pour dériver des courbes de niveau. Mots-clés: courbe de niveau, modèle numérique de terrain, carte topographique, généralisation de la carte.

Published
2021

50. Safety and Efficacy of Venetoclax-Based Treatment in Elderly CLL Patients: A Retrospective Study from the Filo Group

Author

Doublet, Charlotte, primary, Dilhuydy, Marie-Sarah, additional, Ferrant, Emmanuelle, additional, Feugier, Pierre, additional, Fayault, Alexandra, additional, Robert, Philippine, additional, Lepretre, Stephane, additional, Delmer, Alain, additional, Tomowiak, Cécile, additional, Guieze, Romain, additional, Laribi, Kamel, additional, Vignon, Marguerite, additional, Clavert, Aline, additional, Bijou, Fontanet, additional, Re, Daniel, additional, Lara, Diane, additional, Merabet, Fatiha, additional, Tchernonog, Emmanuelle, additional, Dartigeas, Caroline, additional, Michallet, Anne-Sophie, additional, and Quinquenel, Anne, additional

Published
2021
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