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1. Validation of response assessment according to international consortium for MDS/MPN criteria in chronic myelomonocytic leukemia treated with hypomethylating agents

Author

M.L. Chretien, Marie Sebert, Yasmine Chait, Pierre Fenaux, Kamel Laribi, Eric Solary, Thorsten Braun, Uwe Platzbecker, Gruson B, Norbert Vey, Odile Beyne-Rauzy, Sophie Park, Sylvain Pilorge, Laurence Legros, Raphael Itzykson, Pierre-Yves Dumas, Sahnes L, Romain Guieze, Celia Salanoubat, Jean-Baptiste Micol, Matthieu Duchmann, Pierre Hirsch, Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Université Paris-Sud - Paris 11 (UP11), Royal Institute of Technology [Stockholm] (KTH ), 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), CHU Amiens-Picardie, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), 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 (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Pontchaillou [Rennes], Hôpital de Corbeil-ESsonnes, Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe français des myéloplastes and groupe ouest est des leucemies aigües myéloïde (SERVICE DES MALADIES DU SANG), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Antimetabolites, Antineoplastic, education, Azacitidine, Chronic myelomonocytic leukemia, Decitabine, 03 medical and health sciences, 0302 clinical medicine, Myelodysplastic–myeloproliferative diseases, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Letter to the Editor, health care economics and organizations, Aged, Hematology, business.industry, Myelodysplastic syndromes, Translational biology, food and beverages, Leukemia, Myelomonocytic, Chronic, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, DNA Methylation, Middle Aged, medicine.disease, Myelodysplastic-Myeloproliferative Diseases, Survival Analysis, 3. Good health, Response assessment, Leukemia, Treatment Outcome, 030220 oncology & carcinogenesis, Myelodysplastic Syndromes, Immunology, Female, business, 030215 immunology, medicine.drug
Abstract

Validation of response assessment according to international consortium for MDS/MPN criteria in chronic myelomonocytic leukemia treated with hypomethylating agents

Published
2017
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3. Bone complications of mastocytosis: a link between clinical and biological characteristics

Author

Guillaume, N., Desoutter, J., Chandresis, O., Merlusca, L., Henry, I., Georgin-Lavialle, S., Barete, S., Hirsh, I., Bouredji, D., Royer, B., Gruson, B., Lok, C., Seveste, H., Mentaverri, R., Brazier, M., Meynier, J., Hermine, O., J.P., Marolleau, Kamel, Saïd, Pharm, D., Damaj, G., Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Slama, Catherine

Subjects
ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2013

4. IDH1/2 but not DNMT3A mutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the acute leukemia french association

Author

Debarri, H., Lebon, D., Roumier, C., Meyling Cheok, Marceau-Renaut, A., Nibourel, O., Geffroy, S., Helevaut, N., Rousselot, P., Gruson, B., Gardin, C., Chretien, M. L., Sebda, S., Figeac, M., Berthon, C., Quesnel, B., Boissel, N., Castaigne, S., Dombret, H., Renneville, A., and Preudhomme, C.

Subjects
Adult, Neoplasm, Residual, acute myeloid leukemia, Sensitivity and Specificity, DNA Methyltransferase 3A, Young Adult, hemic and lymphatic diseases, Biomarkers, Tumor, Humans, DNA (Cytosine-5-)-Methyltransferases, Aged, Retrospective Studies, Reverse Transcriptase Polymerase Chain Reaction, High-Throughput Nucleotide Sequencing, Nuclear Proteins, Middle Aged, Prognosis, Isocitrate Dehydrogenase, Leukemia, Myeloid, Acute Disease, Mutation, minimal residual disease, next-generation sequencing, France, Neoplasm Recurrence, Local, Clinical Research Paper, Nucleophosmin
Abstract

Acute myeloid leukemia (AML) is a heterogeneous disease. Even within the same NPM1-mutated genetic subgroup, some patients harbor additional mutations in FLT3, IDH1/2, DNMT3A or TET2. Recent studies have shown the prognostic significance of minimal residual disease (MRD) in AML but it remains to be determined which molecular markers are the most suitable for MRD monitoring. Recent advances in next-generation sequencing (NGS) have provided the opportunity to use multiple molecular markers. In this study, we used NGS technology to assess MRD in 31 AML patients enrolled in the ALFA-0701 trial and harboring NPM1 mutations associated to IDH1/2 or DNMT3A mutations. NPM1 mutation-based MRD monitoring was performed by RTqPCR. IDH1/2 and DNMT3A mutations were quantified by NGS using an Ion Torrent Proton instrument with high coverage (2 million reads per sample). The monitoringof IDH1/2 mutations showed that these mutations were reliable MRD markers that allowed the prediction of relapse in the majority of patients. Moreover, IDH1/2 mutation status predicted relapse or disease evolution in 100% of cases if we included the patient who developed myelodysplastic syndrome. In contrast, DNMT3A mutations were not correlated to the disease status, as we found that a preleukemic clone with DNMT3A mutation persisted in 40% of the patients who were in complete remission, reflecting the persistence of clonal hematopoiesis.

5. How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Author

Xavier Cahu, Maxime Desmarets, Thibaut Leguay, Philippe Saas, Victoria Raggueneau, Delphine Binda, Maria Alessandra Rosenthal, Chrystelle Vidal, Olivier Adotevi, Fanny Angelot-Delettre, Françoise Solly, Anne-Cécile Galoisy, Alice Garnier, Sylvie Daliphard, Estelle Guérin, Marie-Pierre Gourin, Karim Maloum, Véronique Harrivel, Edouard Cornet, Felipe Suarez, Jacques Vargaftig, Fabrice Jardin, Caroline Mayeur-Rousse, Sylvain Thepot, Maïder Pagadoy, Thorsten Braun, Bernard Drenou, Yuriy Drebit, Marc Maynadié, Caroline Basle, Zehaira Benseddik, Frédéric Féger, Jean Feuillard, Christian Recher, Etienne Lengliné, Catherine Cordonnier, Rémi Letestu, Mathieu Puyade, Isabelle Arnoux, Remy Gressin, Nathalie Contentin, Jerome Tamburini, Pascale Saussoy, Mary Callanan, Elodie Dindinaud, Pierre-Simon Rohrlich, Julien Guy, Hind Bennani, Tony Petrella, Vincent Foissaud, Johann Rose, Natacha Maillard, Lucile Baseggio, Magali Le Garff-Tavernier, Vincent Barlogis, Denis Guyotat, Yohan Desbrosses, Caroline Bonmati, Damien Roos-Weil, Michel Ticchioni, Sandrine Puyraimond, Norbert Vey, Adriana Plesa, Blandine Guffroy, Daniel Lusina, Bérengère Gruson, Anne Roggy, Véronique Salaun, Eric Deconinck, Jean-Yves Cahn, Nathalie Jacques, Caroline Bret, Florian Renosi, Marie-Christine Béné, Alice Eischen, Stefan Wickenhauser, Benjamin Papoular, Francine Garnache-Ottou, François-Xavier Gros, Vahid Asnafi, Celia Salanoubat, Blandine Bénet, Elisabeth Macintyre, Lou Soret, Orianne Wagner-Ballon, Mohamad Mohty, Elsa Bera, Nicolas Freynet, Ludovic Lhermitte, Franck Trimoreau, Claude Preudhomme, Christophe Roumier, Sébastien Maury, Sabrina Bouyer, Eve Poret, Mikael Roussel, Romaric Lacroix, Christine Arnoulet, Françoise Schillinger, Patricia Okamba, Christine Lefebvre, Didier Blaise, Nicolas Lechevalier, Sabine Brechignac, Christophe Ferrand, Estelle Seilles, Richard Veyrat-Masson, Giorgia Battipaglia, Denis Caillot, Véronique Latger-Cannard, Bruno Quesnel, Didier Bouscary, Sophie Brun, Agathe Debliquis, Marie Loosveld, Franck Geneviève, Carinne Lafon, Lydia Campos, Thierry Fest, Ouda Ghoual, Marie-Christine Jacob, Pierre Peterlin, Valérie Bardet, Anne Arnaud, Véronique Dorvaux, Sabeha Biichle, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-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 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), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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 ), CHU Pontchaillou [Rennes], 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), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), 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, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), European Project: IC18CT980373, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), 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), 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 Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), 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 Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service de biologie hématologique, Garnache-Ottou, F., Vidal, C., Biichle, S., Renosi, F., Poret, E., Pagadoy, M., Desmarets, M., Roggy, A., Seilles, E., Soret, L., Schillinger, F., Puyraimond, S., Petrella, T., Preudhomme, C., Roumier, C., Macintyre, E. A., Harrivel, V., Desbrosses, Y., Gruson, B., Genevieve, F., Thepot, S., Drebit, Y., Leguay, T., Gros, F. -X., Lechevalier, N., Saussoy, P., Salaun, V., Cornet, E., Benseddik, Z., Veyrat-Masson, R., Wagner-Ballon, O., Salanoubat, C., Maynadie, M., Guy, J., Caillot, D., Jacob, M. -C., Cahn, J. -Y., Gressin, R., Rose, J., Quesnel, B., Guerin, E., Trimoreau, F., Feuillard, J., Gourin, M. -P., Plesa, A., Baseggio, L., Arnoux, I., Vey, N., Blaise, D., Lacroix, R., Arnoulet, C., Benet, B., Dorvaux, V., Bret, C., Drenou, B., Debliquis, A., Latger-Cannard, V., Bonmati, C., Bene, M. -C., Peterlin, P., Ticchioni, M., Rohrlich, P. -S., Arnaud, A., Wickenhauser, S., Bardet, V., Brechignac, S., Papoular, B., Raggueneau, V., Vargaftig, J., Letestu, R., Lusina, D., Braun, T., Foissaud, V., Tamburini, J., Bennani, H., Freynet, N., Cordonnier, C., Le Garff-Tavernier, M., Jacques, N., Maloum, K., Roos-Weil, D., Bouscary, D., Asnafi, V., Lhermitte, L., Suarez, F., Lengline, E., Feger, F., Battipaglia, G., Mohty, M., Bouyer, S., Ghoual, O., Dindinaud, E., Basle, C., Puyade, M., Lafon, C., Fest, T., Roussel, M., Cahu, X., Bera, E., Daliphard, S., Jardin, F., Campos, L., Solly, F., Guyotat, D., Galoisy, A. -C., Eischen, A., Mayeur-Rousse, C., Guffroy, B., Recher, C., Loosveld, M., Garnier, A., Barlogis, V., Rosenthal, M. A., Brun, S., Contentin, N., Maury, S., Callanan, M., Lefebvre, C., Maillard, N., Okamba, P., Ferrand, C., Adotevi, O., Saas, P., Angelot-Delettre, F., Binda, D., and Deconinck, E.

Subjects
Oncology, Vincristine, medicine.medical_specialty, Myeloid, Cyclophosphamide, Clinical Trials and Observations, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Plasmacytoid dendritic cell, Immunophenotyping, Clonal Evolution, 03 medical and health sciences, 0302 clinical medicine, Bone Marrow, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Neoplasm Metastasis, Neoplasm Staging, 030304 developmental biology, Chromosome Aberrations, 0303 health sciences, Leukemia, business.industry, Hematopoietic Stem Cell Transplantation, Disease Management, Myeloid leukemia, Dendritic Cells, Hematology, Prognosis, medicine.disease, Blood Cell Count, 3. Good health, Transplantation, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Acute Disease, business, Biomarkers, medicine.drug
Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)–like, acute lymphoid leukemia (ALL)–like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])–like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.

Published
2019
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