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1. When Maxillofacial CBCT Permits Fortuitously to Diagnose Primary Non-Hodgkin’s Lymphoma: A Case Report

Author

Pierre-Louis Polard, Adrian Tempescul, and Karen Vallaeys

Subjects
intrabone malignant non-hodgkin’s lymphoma, maxillary, lymphoma large b-cell diffuse, upper jaw bone radiography, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract

A 47-year-old male with an unremarkable medical history was referred for atypical endodontic pain and treatment of his left upper molars. Clinical and radiographic examinations revealed an extensive, undefined osteolytic area around these teeth. A subsequent bone biopsy diagnosed diffuse large B-cell lymphoma, a high-grade non-Hodgkin’s lymphoma. The hematology team prescribed six cycles of chemotherapy, supplemented by two cycles of methotrexate. Practitioners should be alerted by atypical tooth pain to consider 3D imaging to exclude malignant pathology as early as possible. Teaching point: An atypical tooth pain should alert the practitioner and guide them towards 3D imaging to eliminate diagnostic of malignant pathology as early as possible.

Published
2024
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2. Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial

Author

Kater, Arnon P, Arslan, Önder, Demirkan, Fatih, Herishanu, Yair, Ferhanoglu, Burhan, Diaz, Marcos Gonzalez, Leber, Brian, Montillo, Marco, Panayiotidis, Panayiotis, Rossi, Davide, Skarbnik, Alan, Tempescul, Adrian, Turgut, Mehmet, Mellink, Clemens H, van der Kevie-Kersemaekers, Anne-Marie F, Lanham, Stuart, Sale, Ben, Del Rio, Luis, Popovic, Relja, Chyla, Brenda J, Busman, Todd, Komlosi, Viktor, Wang, Xifeng, Sail, Kavita, Pena, German E, Vizkelety, Tamas, and Forconi, Francesco

Published
2024
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3. Long-term analysis of the RiBVD phase II trial reveals the unfavorable impact of TP53 mutations and hypoalbuminemia in older adults with mantle cell lymphoma; for the LYSA group

Author

Sylvain Carras, Alexia Torroja, Anouk Emadali, Emilie Montaut, Nicolas Daguindau, Adrian Tempescul, Anne Moreau, Emmanuelle Tchernonog, Anna Schmitt, Roch Houot, Caroline Dartigeas, Sarah Barbieux, Selim Corm, Anne Banos, Ludovic Fouillet, Jehan Dupuis, Margaret Macro, Joel Fleury, Fabrice Jardin, Clementine Sarkozy, Ghandi Damaj, Pierre Feugier, Luc Matthieu Fornecker, Cecile Chabrot, Veronique Dorvaux, Krimo Bouabdallah, Sandy Amorim, Reda Garidi, Laurent Voillat, Bertrand Joly, Nadine Morineau, Marie Pierre Moles, Hacene Zerazhi, Jean Fontan, Yazid Arkam, Magda Alexis, Vincent Delwail, Jean Pierre Vilque, Loic Ysebaert, Barbara Burroni, Mary Callanan, Steven Le Gouill, and Rémy Gressin

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

Between 2011 and 2012, a phase II trial evaluated the use of the RiBVD (rituximab, bendamustine, velcade and dexamethasone) combination as first-line treatment for mantle cell lymphoma (MCL) patients over the age of 65. We have now re-examined the classic prognostic factors, adding an assessment of TP53 mutation status. Patients (N=74; median age 73 years) were treated with the RiBVD combination. Median progression-free survival (mPFS) was 79 months and median overall survival (mOS) was 111 months. TP53 mutation status was available for 54/74 (73%) patients. TP53 mutations (TP53mt) were found in 12 patients (22.2%). In multivariate analysis, among the prognostic factors (PF) evaluated, only TP53mt and an albumin level (Alb) 3.6 g/dL were independently associated with a shorter mPFS. A hazard ratio (HR) of 3.16 (1.3-9.9, P=0.014) was obtained for TP53mt versus TP53 wild-type (wt), and 3.6 (1.39-9.5, P=0.009) for Alb

Published
2023
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4. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life—experience of the French Network

Author

Schenone, Laurence, Houillier, Caroline, Tanguy, Marie Laure, Choquet, Sylvain, Agbetiafa, Kossi, Ghesquières, Hervé, Damaj, Gandhi, Schmitt, Anna, Bouabdallah, Krimo, Ahle, Guido, Gressin, Remy, Cornillon, Jérôme, Houot, Roch, Marolleau, Jean-Pierre, Fornecker, Luc-Matthieu, Chinot, Olivier, Peyrade, Frédéric, Bouabdallah, Reda, Moluçon-Chabrot, Cécile, Gyan, Emmanuel, Chauchet, Adrien, Casasnovas, Olivier, Oberic, Lucie, Delwail, Vincent, Abraham, Julie, Roland, Virginie, Waultier-Rascalou, Agathe, Willems, Lise, Morschhauser, Franck, Fabbro, Michel, Ursu, Renata, Thieblemont, Catherine, Jardin, Fabrice, Tempescul, Adrian, Malaise, Denis, Touitou, Valérie, Nichelli, Lucia, Le Garff-Tavernier, Magali, Plessier, Aurélie, Bourget, Philippe, Bonmati, Caroline, Wantz-Mézières, Sophie, Giordan, Quentin, Dorvaux, Véronique, Charron, Cyril, Jabeur, Waliyde, Hoang-Xuan, Khê, Taillandier, Luc, and Soussain, Carole

Published
2022
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5. Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial

Author

Genetica Sectie Genoomdiagnostiek, Kater, Arnon P., Arslan, Önder, Demirkan, Fatih, Herishanu, Yair, Ferhanoglu, Burhan, Diaz, Marcos Gonzalez, Leber, Brian, Montillo, Marco, Panayiotidis, Panayiotis, Rossi, Davide, Skarbnik, Alan, Tempescul, Adrian, Turgut, Mehmet, Mellink, Clemens H., van der Kevie-Kersemaekers, Anne Marie F., Lanham, Stuart, Sale, Ben, Del Rio, Luis, Popovic, Relja, Chyla, Brenda J., Busman, Todd, Komlosi, Viktor, Wang, Xifeng, Sail, Kavita, Pena, German E., Vizkelety, Tamas, Forconi, Francesco, Genetica Sectie Genoomdiagnostiek, Kater, Arnon P., Arslan, Önder, Demirkan, Fatih, Herishanu, Yair, Ferhanoglu, Burhan, Diaz, Marcos Gonzalez, Leber, Brian, Montillo, Marco, Panayiotidis, Panayiotis, Rossi, Davide, Skarbnik, Alan, Tempescul, Adrian, Turgut, Mehmet, Mellink, Clemens H., van der Kevie-Kersemaekers, Anne Marie F., Lanham, Stuart, Sale, Ben, Del Rio, Luis, Popovic, Relja, Chyla, Brenda J., Busman, Todd, Komlosi, Viktor, Wang, Xifeng, Sail, Kavita, Pena, German E., Vizkelety, Tamas, and Forconi, Francesco

Published
2024

7. Long-term efficacy of anti-PD1 therapy in Hodgkin lymphoma with and without allogenic stem cell transplantation

Author

Manson, Guillaume, Mear, Jean-Baptiste, Herbaux, Charles, Schiano, Jean-Marc, Casasnovas, Olivier, Stamatoullas, Aspasia, Deau, Bénédicte, Schmitt, Anna, Garnier, Georges, Regny, Caroline, Bouabdallah, Krimo, Moles-Moreau, Marie-Pierre, Ghesquieres, Hervé, Tempescul, Adrian, Dulery, Remy, Nicolas-Virelizier, Emmanuelle, Delmer, Alain, Borel, Cecile, Chauchet, Adrien, Damotte, Diane, Dercle, Laurent, Brice, Pauline, and Houot, Roch

Published
2019
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8. P1138: COPANLISIB + RITUXIMAB VS RITUXIMAB + PLACEBO IN PATIENTS WITH RELAPSED INDOLENT NON-HODGKIN LYMPHOMA (NHL): UPDATED SAFETY AND EFFICACY FROM THE PHASE III CHRONOS-3 TRIAL

Author

P. L. Zinzani, M. Özcan, K. Sapunarova, W. Jurczak, A. Hamed, K. Bouabdallah, G. Saydam, K. Geissler, Á. Szomor, M. Lazaroiu, A. Salar, A. Tempescul, M. Nalcaci, L. Gercheva, M. Egyed, P. Panayiotidis, L. Mongay Soler, A. Cao, C. Phelps, B. H Childs, and M. J Matasar

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2022
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9. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study

Author

Casasnovas, René-Olivier, Bouabdallah, Reda, Brice, Pauline, Lazarovici, Julien, Ghesquieres, Hervé, Stamatoullas, Aspasia, Dupuis, Jehan, Gac, Anne-Claire, Gastinne, Thomas, Joly, Bertrand, Bouabdallah, Krimo, Nicolas-Virelizier, Emmanuelle, Feugier, Pierre, Morschhauser, Franck, Delarue, Richard, Farhat, Hassan, Quittet, Philippe, Berriolo-Riedinger, Alina, Tempescul, Adrian, Edeline, Véronique, Maisonneuve, Hervé, Fornecker, Luc-Matthieu, Lamy, Thierry, Delmer, Alain, Dartigues, Peggy, Martin, Laurent, André, Marc, Mounier, Nicolas, Traverse-Glehen, Alexandra, and Meignan, Michel

Published
2019
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10. STIM1 at the plasma membrane as a new target in progressive chronic lymphocytic leukemia

Author

Marjolaine Debant, Miguel Burgos, Patrice Hemon, Paul Buscaglia, Tinhinane Fali, Sarra Melayah, Nelig Le Goux, Christophe Vandier, Marie Potier-Cartereau, Jacques-Olivier Pers, Adrian Tempescul, Christian Berthou, Cristina Bagacean, Olivier Mignen, and Yves Renaudineau

Subjects
CLL, STIM1, Constitutive Ca2+ entry, Disease outcome, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Dysregulation in calcium (Ca2+) signaling is a hallmark of chronic lymphocytic leukemia (CLL). While the role of the B cell receptor (BCR) Ca2+ pathway has been associated with disease progression, the importance of the newly described constitutive Ca2+ entry (CE) pathway is less clear. In addition, we hypothesized that these differences reflect modifications of the CE pathway and Ca2+ actors such as Orai1, transient receptor potential canonical (TRPC) 1, and stromal interaction molecule 1 (STIM1), the latter being the focus of this study. Methods An extensive analysis of the Ca2+ entry (CE) pathway in CLL B cells was performed including constitutive Ca2+ entry, basal Ca2+ levels, and store operated Ca2+ entry (SOCE) activated following B cell receptor engagement or using Thapsigargin. The molecular characterization of the calcium channels Orai1 and TRPC1 and to their partner STIM1 was performed by flow cytometry and/or Western blotting. Specific siRNAs for Orai1, TRPC1 and STIM1 plus the Orai1 channel blocker Synta66 were used. CLL B cell viability was tested in the presence of an anti-STIM1 monoclonal antibody (mAb, clone GOK) coupled or not with an anti-CD20 mAb, rituximab. The Cox regression model was used to determine the optimal threshold and to stratify patients. Results Seeking to explore the CE pathway, we found in untreated CLL patients that an abnormal CE pathway was (i) highly associated with the disease outcome; (ii) positively correlated with basal Ca2+ concentrations; (iii) independent from the BCR-PLCγ2-InsP3R (SOCE) Ca2+ signaling pathway; (iv) supported by Orai1 and TRPC1 channels; (v) regulated by the pool of STIM1 located in the plasma membrane (STIM1PM); and (vi) blocked when using a mAb targeting STIM1PM. Next, we further established an association between an elevated expression of STIM1PM and clinical outcome. In addition, combining an anti-STIM1 mAb with rituximab significantly reduced in vitro CLL B cell viability within the high STIM1PM CLL subgroup. Conclusions These data establish the critical role of a newly discovered BCR independent Ca2+ entry in CLL evolution, provide new insights into CLL pathophysiology, and support innovative therapeutic perspectives such as targeting STIM1 located at the plasma membrane.

Published
2019
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11. Prognostic value of end-of-induction PET response after first-line immunochemotherapy for follicular lymphoma (GALLIUM): secondary analysis of a randomised, phase 3 trial

Author

Hertzberg, Mark, Grigg, Andrew, Cannell, Paul, Quach, Hang, Opat, Stephen, Tam, Constantine, Marlton, Paula, Janssens, Ann, Offner, Fritz, Van eygen, Koen, Sangha, Randeep, Mckay, Pam, Wilson, Jonathan, Van Der Jagt, Richard, Roitman, Daryl, Trneny, Marek, Mayer, Jiri, Le Du, Katell, Solal-Celigny, Philippe, Cartron, Guillaume, Foussard, Charles, Frickhofen, Norbert, Schmidt, Peter, Graeven, Ullrich, Gaska, Tobias, Schlag, Rudolf, Sökler, Martin, Prange-Krex, Gabriele, Florschütz, Axel, Lindemann, Hans-Walter, Schimmelpfennig, Christoph, Tonndorf, Solveig, Hänel, Mathias, Hess, Georg, Schalk, Enrico, Hütten, Heiko, Doelken, Gottfried, Pfreundschuh, Michael, Keller, Ulrich, Herold, Michael, Forstpointner, Roswitha, Vehling-Kaiser, Ursula, Hoffmann, Martin, Borbenyi, Zita, Udvardy, Miklos, Demeter, Judit, Rambaldi, Alessandro, Morra, Enrica, Massimo, Federico, Majolino, Ignazio, Balzarotti, Monica, Semenzato, Gianpietro, Canales Albendea, Miguel Angel, Peñalver Parraga, Francisco Javier, Soler Campos, Alfonso, Sancho Cia, Juan Manuel, Marquez Navarro, Jose Antonio, Grande Garcia, Carlos, Nilsson-Ehle, Herman, Mccarthy, Helen, Pocock, Chris, Sadullah, Shalal, Malladi, Ram, Radford, John, Kanfer, Ed, Kruger, Anton, Culligan, Dominic, Dyer, Martin, Pettengell, Ruth, Seymour, John, Gribben, John, Al-Ismail, Saad, Al-Refaie, Faris, Blesing, Norbert, Macnamara, Christopher, O'callaghan, Ann, Haynes, Andrew, Follows, George, Johnson, Roderick, Cunningham, David, Bowles, Kristian, Collins, Graham, Gallop-Evans, Eve, Robinson, Stephen, Subash, Chezhian, Bailey, James, Holden, Viran, Neidhart, Jeffrey, De Oliveira, Moacyr, Tezcan, Haluk, Kim, Kevin, Kambhampati, Suman, Lanier, Keith, Mcclean, John, Tobinai, Kensei, Hatake, Kiyohiko, Ogura, Michinori, Uchida, Toshiki, Ando, Kiyoshi, Kinoshita, Tomohiro, Höhler, Thomas, Stauder, Heribert, Kirsch, Andreas, Koenigsmann, Michael, Kremers, Stephan, Illmer, Thomas, Witzens-Harig, Mathias, La Roseé, Paul, Dürig, Jan, Kneba, Michael, Hensel, Manfred, Fuxius, Stefan, Bergmann, Lothar, Hübel, Kai, Buske, Christian, Marks, Reinhard, Wulf, Gerald, Lerchenmueller, Christian, Schmits, Rudolf, Reinwald, Mark, Lengfelder, Eva, Scott, Fiona, Chou, Takaaki, Taniwaki, Masafumi, Yoshida, Isao, Ishizawa, Kenichi, Uike, Naokuni, Uoshima, Nobuhiko, Kamitsuji, Yuri, Iida, Shinsuke, Ohmine, Ken, Nosaka, Kisato, Ide, Kazuhiko, Ishikawa, Takayuki, Desjardins, Pierre, Finn, Nicholas, Zhu, Jun, Li, Wei, Yu, Li, Ren, Hanyun, Shi, Yuan Kai, Wu, Gang, Hong, Xiaonan, Zhang, Qingyuan, Feng, Jifeng, Zhan, Rong, Lin, Tongyu, Leppa, Sirpa, Costello, Regis, Tempescul, Adrian, Sanhes, Laurence, Tournilhac, Olivier, Kirchen, Heinz, Hebart, Holger, Weide, Rudolf, Jentsch-Ullrich, Kathleen, Avivi, Irit, Nagler, Arnon, Gurion, Ronit, Shpilberg, Ofer, Leoni, Pietro, Baldini, Luca, Samoylova, Olga, Myasnikov, Alexandr, Tan, Tran-Der, Chang, Hung, Kumagai, Kyoya, Tsukamoto, Norifumi, Tsukasaki, Kunihiro, Beatty, Patrick, Usui, Noriko, Izutsu, Koji, Murayama, Tohru, Ichinohe, Tatsuo, Kubo, Kohmei, Ishida, Fumihiro, Beck, J. Thaddeus, Griesinger, Frank, Osmanov, Dzhelil, Dakhil, Shaker, Clavert, Aline, Maruyama, Dai, Terui, Yasuhito, Yamamoto, Kazuhito, Eigendorff, Ekkehard, Kobayashi, Tsutomu, Ichikawa, Satoshi, Choi, Ilseung, Wada, Katsuya, Kikukawa, Yoshitaka, Matsuoka, Masao, Yoshino, Takayuki, Minami, Yosuke, Trotman, Judith, Barrington, Sally F, Belada, David, Meignan, Michel, MacEwan, Robert, Owen, Carolyn, Ptáčník, Václav, Rosta, András, Fingerle-Rowson, Günter R, Zhu, Jiawen, Nielsen, Tina, Sahin, Deniz, Hiddemann, Wolfgang, Marcus, Robert E, and Davies, Andrew

Published
2018
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12. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial

Author

Facon, Thierry, Dimopoulos, Meletios A., Meuleman, Nathalie, Belch, Andrew, Mohty, Mohamad, Chen, Wen-Ming, Kim, Kihyun, Zamagni, Elena, Rodriguez-Otero, Paula, Renwick, William, Rose, Christian, Tempescul, Adrian, Boyle, Eileen, Manier, Salomon, Attal, Michel, Moreau, Philippe, Macro, Margaret, Leleu, Xavier, Lorraine Chretien, Marie, Ludwig, Heinz, Guo, Shien, Sturniolo, Michael, Tinel, Antoine, Silvia Monzini, Mara, Costa, Bruno, Houck, Vanessa, Hulin, Cyrille, and Yves Mary, Jean

Published
2020
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13. MicroRNAs Associated With a Good Prognosis of Acute Myeloid Leukemia and Their Effect on Macrophage Polarization

Author

Alexandra Neaga, Cristina Bagacean, Adrian Tempescul, Laura Jimbu, Oana Mesaros, Cristina Blag, Ciprian Tomuleasa, Corina Bocsan, Mihaela Gaman, and Mihnea Zdrenghea

Subjects
acute myeloid leukemia, non-coding RNAs, macrophages (M1/M2), macrophage polarization, tumor suppressor microRNA, Immunologic diseases. Allergy, RC581-607
Abstract

Acute myeloid leukemia (AML) is an aggressive myeloid malignancy with poor outcomes despite very intensive therapeutic approaches. For the majority of patients which are unfit and treated less intensively, the prognosis is even worse. There has been unspectacular progress in outcome improvement over the last decades and the development of new approaches is of tremendous interest. The tumor microenvironment is credited with an important role in supporting cancer growth, including leukemogenesis. Macrophages are part of the tumor microenvironment and their contribution in this setting is increasingly being deciphered, these cells being credited with a tumor supporting role. Data on macrophage role and polarization in leukemia is scarce. MicroRNAs (miRNAs) have a role in the post-transcriptional regulation of gene expression, by impending translation and promoting degradation of messenger RNAs. They are important modulators of cellular pathways, playing major roles in normal hematopoietic differentiation. miRNA expression is significantly correlated with the prognosis of hematopoietic malignancies, including AML. Oncogenic miRNAs correlate with poor prognosis, while tumor suppressor miRNAs, which inhibit the expression of proto-oncogenes, are correlated with a favorable prognosis. miRNAs are proposed as biomarkers for diagnosis and prognosis and are regarded as therapeutic approaches in many cancers, including AML. miRNAs with epigenetic or modulatory activity, as well as with synergistic activity with chemotherapeutic agents, proved to be promising therapeutic targets in experimental, pre-clinical approaches. The clinical availability of emerging compounds with mimicking or suppressor activity provides the opportunity for future therapeutic targeting of miRNAs. The present paper is focusing on miRNAs which, according to current knowledge, favorably impact on AML outcomes, being regarded as tumor suppressors, and reviews their role in macrophage polarization. We are focusing on miRNA expression in the setting of AML, but data on correlations between miRNA expression and macrophage polarization is mostly coming from studies involving normal tissue.

Published
2021
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14. 17p deletion strongly influences rituximab elimination in chronic lymphocytic leukemia

Author

Cristina Bagacean, Adrian Tempescul, David Ternant, Anne Banet, Nathalie Douet-Guilbert, Anne Bordron, Boutahar Bendaoud, Hussam Saad, Mihnea Zdrenghea, Christian Berthou, Gilles Paintaud, and Yves Renaudineau

Subjects
Chronic lymphocytic leukemia, Anti-CD20 monoclonal antibody, Rituximab, Pharmacokinetics, Clearance, 17p deletion, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Chronic lymphocytic leukemia (CLL) is the most common type of leukemia and the anti-CD20 monoclonal antibody, rituximab, represents the therapeutic gold standard for more than 2 decades in this pathology, when used in combination with chemotherapy. However, some patients experience treatment resistance or rapid relapses, and in particular, those harboring a 17p/TP53 deletion (del(17p)). This resistance could be explained by a chemo-resistance, but it could also result from the direct impact of del(17p) on the pharmacokinetics of rituximab, which represents the aim of the present study. Accordingly, 44 CLL patients were included in the study, and among them 9 presented a del(17p). Next, a total of 233 rituximab sera were selected for a pharmacokinetic study and analyzed in a two-compartment model showing important differences when del(17p) CLL patients were compared with non-del(17p) patients treated with rituximab and chemotherapy: (1) clearance of rituximab was faster; (2) central volume of rituximab distribution V1 (peripheral blood) was reduced while peripheral volume V2 (lymphoid organs and tissues) was increased; and (3) the rate of rituximab elimination (Kout) was faster. In contrast, the group with a better prognosis harboring isolated del(13q) presented a slower rate of elimination (Kout). Pharmacokinetic parameters were independent from the other factors tested such as age, sex, chemotherapy regimen (fludarabine/cyclophosphamide versus bendamustine), IGHV mutational status, and FCGR3A 158VF status. In conclusion, this study provides an additional argument to consider that del(17p) is effective not only to control chemoresistance but also monoclonal antibody activity, based on higher rituximab turnover.

Published
2019
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15. Management and outcome of primary CNS lymphoma in the modern era: An LOC network study

Author

Houillier, Caroline, Soussain, Carole, Ghesquières, Hervé, Soubeyran, Pierre, Chinot, Olivier, Taillandier, Luc, Lamy, Thierry, Choquet, Sylvain, Ahle, Guido, Damaj, Gandhi, Agapé, Philippe, Moluçon-Chabrot, Cécile, Amiel, Alexandra, Delwail, Vincent, Fabbro, Michel, Jardin, Fabrice, Chauchet, Adrien, Moles-Moreau, Marie-Pierre, Morschhauser, Franck, Casasnovas, Olivier, Gressin, Rémy, Fornecker, Luc-Matthieu, Abraham, Julie, Marolleau, Jean-Pierre, Tempescul, Adrian, Campello, Chantal, Colin, Philippe, Tamburini, Jérôme, Laribi, Kamel, Serrier, Caroline, Haioun, Corinne, Chebrek, Safia, Schmitt, Anna, Blonski, Marie, Houot, Roch, Boyle, Eileen, Bay, Jacques-Olivier, Oberic, Lucie, Tabouret, Emeline, Waultier, Agathe, Martin-Duverneuil, Nadine, Touitou, Valérie, Cassoux, Nathalie, Kas, Aurélie, Mokhtari, Karima, Charlotte, Frederic, Alentorn, Agusti, Feuvret, Loïc, Le Garff-Tavernier, Magali, Costopoulos, Myrto, Mathon, Bertrand, Peyre, Matthieu, Delgadillo, Daniel, Douzane, Hassen, Genet, Diane, Aidaoui, Bachir, Hoang-Xuan, Khê, and Gyan, Emmanuel

Published
2020
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16. Combining cytogenetic and epigenetic approaches in chronic lymphocytic leukemia improves prognosis prediction for patients with isolated 13q deletion

Author

Cristina Bagacean, Christelle Le Dantec, Christian Berthou, Adrian Tempescul, Hussam Saad, Anne Bordron, Mihnea Zdrenghea, Victor Cristea, Nathalie Douet-Guilbert, and Yves Renaudineau

Subjects
Chronic lymphocytic leukemia, Cytogenetics, DNA methylation, Active DNA demethylation, DNMT, TET, Medicine, Genetics, QH426-470
Abstract

Abstract Background Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established. Methods CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints]). The two 5-cytosine derivatives, 5-methylcytosine (5-mCyt) and 5-hydroxymethylcytosine (5-hmCyt), were tested by ELISA (n = 60), while real-time quantitative PCR was used for determining transcriptional expression levels of DNMT and TET (n = 24). Results By using global DNA methylation/demethylation levels, in the low-risk disease group, two subgroups with significantly different clinical outcomes have been identified (median treatment-free survival [TFS] 45 versus > 120 months for 5-mCyt, p = 0.0008, and 63 versus > 120 months for 5-hmCyt, p = 0.04). A defective 5-mCyt status was further associated with a higher percentage of 13q deleted nuclei (> 80%), thus suggesting an acquired process. When considering the cytogenetic intermediate/high-risk disease groups, an association of 5-mCyt status with lymphocytosis (p = 0.0008) and the lymphocyte doubling time (p = 0.04) but not with TFS was observed, as well as a reduction of DNMT3A, TET1, and TET2 transcripts. Conclusions Combining cytogenetic studies with 5-mCyt assessment adds accuracy to CLL patients’ prognoses and particularly for those with 13q deletion as a sole cytogenetic abnormality.

Published
2017
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17. Long‐term analysis of the RiBVD phase II trial reveals the unfavorable impact of TP53 mutations and hypoalbuminemia in elderly mantle cell lymphoma patients. For the LYSA group.

Author

Carras, S., primary, Torroja, A., additional, Emadali, A., additional, Daguindau, N., additional, Tempescul, A., additional, Macro, M., additional, Moreau, A., additional, Tchernonog, E., additional, Houot, R., additional, Schmitt, A., additional, Dartigeas, C., additional, Dupuis, J., additional, Jardin, F., additional, Banos, A., additional, Corm, S., additional, Barbieux, S., additional, Zerazhi, H., additional, Arkam, Y., additional, Fouillet, L., additional, Fontan, J., additional, Vilque, J., additional, Moles, M., additional, Sarkozy, C., additional, Morineau, N., additional, Joly, B., additional, Voillat, L., additional, Alexis, M., additional, Fornecker, L. M., additional, Garidi, R., additional, Amorim, S., additional, Bouabdallah, K., additional, Dorvaux, V., additional, Chabrot, C., additional, Feugier, P., additional, Damaj, G., additional, Fleury, J., additional, Delwail, V., additional, Ysebaert, L., additional, Burroni, B., additional, Callanan, M., additional, Legouill, S., additional, and Gressin, R., additional

Published
2023
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18. The regulatory capacity of B cells directs the aggressiveness of CLL

Author

Audrey Mohr, Marie Cumin, Cristina Bagacean, Pierre Pochard, Christelle Le Dantec, Sophie Hillion, Yves Renaudineau, Christian Berthou, Adrian Tempescul, Hussam Saad, Jacques-Olivier Pers, Anne Bordron, and Christophe Jamin

Subjects
regulatory capacity, b cells, cll, aggressiveness, tlr9, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Chronic lymphocytic leukemia (CLL) is associated with abnormal T-cell responses responsible for defective anti-tumor activities. Intriguingly, CLL B cells share phenotypical characteristics with regulatory B (Breg) cells suggesting that they might negatively control the T-cell activation and immune responses. We elaborated an in vitro co-culture system with T cells to evaluate the Breg capacities of CLL B cells following innate Toll-like receptor 9 (TLR9) engagement. We demonstrated that B cells from half of the patients exhibited regulatory capacities, whilst B cells from the remaining patients were unable to develop a Breg function. The T cell sensitivities of all patients were normal suggesting that defective Breg activities were due to intrinsic CLL B cell deficiencies. Thus, TLR-dedicated gene assays highlighted differential signature of the TLR9 negative regulation pathway between the two groups of patients. Furthermore, correlations of the doubling time of lymphocytosis, the time to first treatment, the mutational status of IgVH and the Breg functions indicate that patients with efficient Breg activities have more aggressive CLL than patients with defective Breg cells. Our in vitro observations may open new approaches for adjusting therapeutic strategies targeting the Breg along with the evolution of the disease.

Published
2019
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20. Autologous hematopoietic stem cell transplantation in elderly patients (≥ 70 years) with non-Hodgkin's lymphoma: A French Society of Bone Marrow Transplantation and Cellular Therapy retrospective study

Author

Hermet, E., Cabrespine, A., Guièze, R., Garnier, A., Tempescul, A., Lenain, P., Bouabdallah, R., Vilque, J.P., Frayfer, J., Bordessoule, D., Sibon, D., Janvier, M., Caillot, D., Biron, P., Legros, L., Choufi, B., Drenou, B., Gorin, N.C., Bilger, K., Tamburini, J., Soussain, C., Brechignac, S., and Bay, J.O.

Published
2015
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21. A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma

Author

Rémy Gressin, Nicolas Daguindau, Adrian Tempescul, Anne Moreau, Sylvain Carras, Emmanuelle Tchernonog, Anna Schmitt, Roch Houot, Caroline Dartigeas, Jean Michel Pignon, Selim Corm, Anne Banos, Christiane Mounier, Jehan Dupuis, Margaret Macro, Joel Fleury, Fabrice Jardin, Clementine Sarkozy, Ghandi Damaj, Pierre Feugier, Luc Matthieu Fornecker, Cecile Chabrot, Veronique Dorvaux, Krimo Bouadallah, Sandy Amorin, Reda Garidi, Laurent Voillat, Bertrand Joly, Philippe Solal Celigny, Nadine Morineau, Marie Pierre Moles, Hacene Zerazhi, Jean Fontan, Yazid Arkam, Magda Alexis, Vincent Delwail, Jean Pierre Vilque, Loic Ysebaert, Steven Le Gouill, Mary B. Callanan, and for the Lymphoma Study Association

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

We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression, [18F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively (P

Published
2019
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23. Non-adherence to treatment with cytoreductive and/or antithrombotic drugs is frequent and associated with an increased risk of complications in patients with polycythemia vera or essential thrombocythemia (OUEST study)

Author

Ronan Le Calloch, Karine Lacut, Christelle Le Gall-Ianotto, Emmanuel Nowak, Morgane Abiven, Adrian Tempescul, Florence Dalbies, Jean-Richard Eveillard, Valérie Ugo, Stéphane Giraudier, Gaëlle Guillerm, Eric Lippert, Christian Berthou, and Jean-Christophe Ianotto

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

The purpose of this study was to identify the incidence, causes and impact of non-adherence to oral and subcutaneous chronic treatments for patients with polycythemia vera or essential thrombocythemia. Patients receiving cytoreductive drugs for polycythemia vera or essential thrombocythemia were recruited at our institution (Observatoire Brestois des Néoplasies Myéloprolifératives registry). They completed a one-shot questionnaire designed by investigators (Etude de l’Observance Thérapeutique et des Effets Secondaires des Traitements study). Data about complications (thrombosis, transformation and death) at any time in the patient’s life (before diagnosis, up until consultation and after the completion of the questionnaire) were collected. Sixty-five (22.7%) of 286 patients reported poor adherence (

Published
2018
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25. Isolated intraocular relapses of primary cerebral lymphomas: An loc network study

Author

Nadia Younan, Carole Soussain, Sylvain Choquet, Nathalie Cassoux, Valérie Touitou, Anna Schmitt, Olivier Chinot, Lucie Oberic, Gandhi Damaj, Roch Houot, Hervé Ghesquières, Kamel Laribi, Guido Ahle, Luc Taillandier, Jérôme Paillassa, Emmanuel Gyan, Fabrice Jardin, Vincent Delwail, Jean‐Pierre Marolleau, Adrian Tempescul, Philippe Agapé, Marie Bourniquel, Fabienne Vacheret, Ibrahim Jdid, Magali Le Garff‐Tavernier, Denis Malaise, Agusti Alentorn, Khê Hoang Xuan, Caroline Houillier, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Curie - Saint Cloud (ICSC), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], Institut Bergonié [Bordeaux], UNICANCER, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Le Mans (CH Le Mans), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), 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), 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), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Service d'Hématologie [CH Perpignan], CH Perpignan, CHU Orléans, Département d'Oncologie Chirurgicale [Institut Curie], Laboratoire d'Imagerie Translationnelle en Oncologie (LITO ), 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), DESSAIVRE, Louise, Service d'Onco-neurologie = Département de neurologie 2 [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), Service d'Ophtalmologie [CHU Pitié-Salpêtrière], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], and 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)

Subjects
relapse, Cancer Research, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, primary CNS lymphoma, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, ocular lymphoma, hemic and lymphatic diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, General Medicine, prognosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Most relapses of primary central nervous system lymphoma (PCNSL) occur in the brain and are associated with a poor prognosis. Isolated intraocular relapses (IIORs) are rare and poorly described. We retrospectively selected from the French Lymphome Oculo-Cérébral database PCNSL patients who initially presented with cerebral localization and who experienced IIOR during the course of the disease. Of the 1472 patients included in the database, 55 patients presented an IIOR. Their median age was 68 years, and median Karnofsky Performance Status 80. IL-10 levels in the aqueous humor and/or in the vitreous were increased in 42/46 patients. 45/55 patients received systemic chemotherapy, and 11/55 received high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) as consolidation treatment. After a median follow-up of 69 months, 42/55 patients had relapsed, including 90% of the patients who did not receive HCT-ASCT at IIOR and 40% of the patients who received HCT-ASCT at IIOR (p 0.001). The first relapse after the initial IIOR was exclusively in the eye in 23/42 patients, and 29/42 patients had a subsequent brain relapse during the course of the disease. The median progression-free survival, brain-free survival and overall survival from IIOR were 12.2, 48.6 and 57.1 months, respectively. Isolated intraocular relapse is not exceptional in the course of PCNSL and deserves systematic ophthalmological follow-up. Its prognosis is much better than the prognosis of brain relapse, with an evolution close to that of primary vitreoretinal lymphoma. With the exception of patients who received HCT-ASCT at IIOR, almost all patients subsequently relapsed, often with other IIORs.

Published
2022
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26. Identification of altered cell signaling pathways using proteomic profiling in stable and progressive chronic lymphocytic leukemia

Author

Christelle Le Dantec, Cristina Adela Iuga, Ioana-Ecaterina Pralea, Melanie Cornen, Wesley H. Brooks, Jacques-Olivier Pers, Hussam Saad, Tiffany Bergot, Adrian Tempescul, Anne Bordron, Delphine G. Bernard, Jean-Christophe Ianotto, Cristina Bagacean, Mihnea Zdrenghea, Christian Berthou, Yves Renaudineau, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Technical University of Cluj-Napoca, Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), University of South Florida [Tampa] (USF), Iuliu Hatieganu University of Medicine & Pharmacy, The authors express thanks to the 'Ligue contre le cancer,' 'Region Bretagne,' sections 29/35/49 for partially funding this study, and Touzanné, Gisèle

Subjects
Male, MESH: Leukemia, Lymphocytic, Chronic, B-Cell / genetics, Proteome, [SDV]Life Sciences [q-bio], Chronic lymphocytic leukemia, Disease, Stable Disease, hemic and lymphatic diseases, Immunology and Allergy, Longitudinal Studies, RNA-Seq, liquid chromatography-tandem mass spectrometry, MESH: Leukemia, Lymphocytic, Chronic, B-Cell / pathology, MESH: Longitudinal Studies, Wnt Signaling Pathway, B-Lymphocytes, MESH: Middle Aged, Wnt signaling pathway, MESH: Follow-Up Studies, MESH: Gene Expression Regulation, Neoplastic, Middle Aged, Cell cycle, Prognosis, Gene Expression Regulation, Neoplastic, [SDV] Life Sciences [q-bio], MESH: B-Lymphocytes / metabolism, RNA splicing, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, cell cycle, [SDV.IMM] Life Sciences [q-bio]/Immunology, RNA Splicing, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, splicing, Biology, MESH: Prognosis, MESH: Leukemia, Lymphocytic, Chronic, B-Cell / metabolism, MESH: Biomarkers, Tumor / genetics, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, medicine, Humans, Aged, Retrospective Studies, Proteomic Profile, Proteomic Profiling, Cell Biology, MESH: B-Lymphocytes / pathology, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, MESH: Male, Cancer research, chronic lymphocytic leukemia, MESH: Female, Follow-Up Studies
Abstract

Chronic lymphocytic leukemia (CLL) is characterized by significant biologic and clinical heterogeneity. This study was designed to explore CLL B-cells’ proteomic profile in order to identify biologic processes affected at an early stage and during disease evolution as stable or progressive. Purified B cells from 11 untreated CLL patients were tested at two time points by liquid chromatography–tandem mass spectrometry. Patients included in the study evolved to either progressive (n = 6) or stable disease (n = 5). First, at an early stage of the disease (Binet stage A), based on the relative abundance levels of 389 differentially expressed proteins (DEPs), samples were separated into stable and progressive clusters with the main differentiating factor being the RNA splicing pathway. Next, in order to test how the DEPs affect RNA splicing, a RNA-Seq study was conducted showing 4217 differentially spliced genes between the two clusters. Distinct longitudinal evolutions were observed with predominantly proteomic modifications in the stable CLL group and spliced genes in the progressive CLL group. Splicing events were shown to be six times more frequent in the progressive CLL group. The main aberrant biologic processes controlled by DEPs and spliced genes in the progressive group were cytoskeletal organization, Wnt/β-catenin signaling, and mitochondrial and inositol phosphate metabolism with a downstream impact on CLL B-cell survival and migration. This study suggests that proteomic profiles at the early stage of CLL can discriminate progressive from stable disease and that RNA splicing dysregulation underlies CLL evolution, which opens new perspectives in terms of biomarkers and therapy.

Published
2021
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27. Isolated intraocular relapses of primary cerebral lymphomas: An LOC network study

Author

Younan, Nadia, primary, Soussain, Carole, additional, Choquet, Sylvain, additional, Cassoux, Nathalie, additional, Touitou, Valérie, additional, Schmitt, Anna, additional, Chinot, Olivier, additional, Oberic, Lucie, additional, Damaj, Gandhi, additional, Houot, Roch, additional, Ghesquières, Hervé, additional, Laribi, Kamel, additional, Ahle, Guido, additional, Taillandier, Luc, additional, Paillassa, Jérôme, additional, Gyan, Emmanuel, additional, Jardin, Fabrice, additional, Delwail, Vincent, additional, Marolleau, Jean‐Pierre, additional, Tempescul, Adrian, additional, Agapé, Philippe, additional, Bourniquel, Marie, additional, Vacheret, Fabienne, additional, Jdid, Ibrahim, additional, Le Garff‐Tavernier, Magali, additional, Malaise, Denis, additional, Alentorn, Agusti, additional, Xuan, Khê Hoang, additional, and Houillier, Caroline, additional

Published
2022
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28. P1138: COPANLISIB + RITUXIMAB VS RITUXIMAB + PLACEBO IN PATIENTS WITH RELAPSED INDOLENT NON-HODGKIN LYMPHOMA (NHL): UPDATED SAFETY AND EFFICACY FROM THE PHASE III CHRONOS-3 TRIAL

Author

Zinzani, P. L., primary, Özcan, M., additional, Sapunarova, K., additional, Jurczak, W., additional, Hamed, A., additional, Bouabdallah, K., additional, Saydam, G., additional, Geissler, K., additional, Szomor, Á., additional, Lazaroiu, M., additional, Salar, A., additional, Tempescul, A., additional, Nalcaci, M., additional, Gercheva, L., additional, Egyed, M., additional, Panayiotidis, P., additional, Mongay Soler, L., additional, Cao, A., additional, Phelps, C., additional, H Childs, B., additional, and J Matasar, M., additional

Published
2022
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29. Ki67 Immunohistochemical Expression Level ≥70%, Bulky Presentation ≥7.5 cm, Meningeal Lymphomatosis, and Interim PET ΔSUVmax After 4 Treatment Cycles <71% as Parts of a Practical Scoring System to Predict Progression-Free Survival and Overall Survival in Diffuse Large B-Cell Lymphoma

Author

Vincent Rebière, Meriem Maajem, Ronan Le Calloch, Leela Raj, Anne-Sophie Le Bris, Mohamed Malou, François Salmon, Isabelle Quintin-Roué, Adrian Tempescul, David Bourhis, Laura Samaison, Hussam Saad, Pierre-Yves Salaun, Christian Berthou, Jean-Christophe Ianotto, Ronan Abgral, and Jean-Richard Eveillard

Abstract

Currently, prognostic models in diffuse large B-cell lymphoma (DLBCL) fail to closely reflect patients' biological, clinical, and survival heterogeneity. We, therefore, assessed the impact of clinical, biological, immunohistochemical (IHC), baseline (0), and interim (after 2 and 4 treatment cycles) PET (PET0, PET2, and PET4) data not yet included in any scoring system on DLBCL outcome. The analysis was conducted on 89 previously untreated adult patients of the Finistere Observatory Cohort (O.Ly.Fin) with documented DLBCL, recruited between January 2010 and December 2017, with progression-free survival (PFS) and overall survival (OS) as primary and secondary endpoints, respectively. Seventy-eight patients were treated with rituximab, cyclophosphamide, hydroxyadriamycin, vincristine, and prednisone (R-CHOP), while 11 received R-dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and hydroxyadriamycin (EPOCH). Patients were followed up until June 20, 2020. On multivariate analysis, Ki67 ≥ 70% on IHC (K), bulky presentation ≥7.5 cm (B), meningeal lymphomatosis (M), and PET0–PET4 ΔSUVmax de novo DLBCL patients.

Published
2022
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33. Ki67 Immunohistochemical Expression Level ≥70%, Bulky Presentation ≥7.5 cm, Meningeal Lymphomatosis, and Interim PET ΔSUVmax After 4 Treatment Cycles <71% as Parts of a Practical Scoring System to Predict Progression-Free Survival and Overall Survival in Diffuse Large B-Cell Lymphoma

Author

Rebière, Vincent, primary, Maajem, Meriem, additional, Le Calloch, Ronan, additional, Raj, Leela, additional, Le Bris, Anne-Sophie, additional, Malou, Mohamed, additional, Salmon, François, additional, Quintin-Roué, Isabelle, additional, Tempescul, Adrian, additional, Bourhis, David, additional, Samaison, Laura, additional, Saad, Hussam, additional, Salaun, Pierre-Yves, additional, Berthou, Christian, additional, Ianotto, Jean-Christophe, additional, Abgral, Ronan, additional, and Eveillard, Jean-Richard, additional

Published
2022
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34. Prognostic value of interim FDG PET-CT in patients older than 60 years with diffuse large B-cell lymphoma treated by PMitCEBO plus rituximab. Comparison between Deauville 5-point scale and International Harmonization Project criteria

Author

Naelle LOMBION, Philippe ROBIN, Adrian TEMPESCUL, Pierre-Yves LE ROUX, Ulrike SCHICK, Gaëlle GUILLERM, Jean-Christophe IANOTTO, Christian BERTHOU, Pierre-Yves SALAÜN, Ronan ABGRAL, Department of Clinical Hematology, Institute of Cancerology and Hematology, CHU Morvan, CHRU Brest - Service de médecine nucléaire (CHU - BREST - Med Nucléaire), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Laboratoire de Traitement de l'Information Medicale (LaTIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), and Calvez, Ghislaine

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV]Life Sciences [q-bio], Prednisolone, Prognosis, [SDV] Life Sciences [q-bio], Bleomycin, Fluorodeoxyglucose F18, Vincristine, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Antineoplastic Combined Chemotherapy Protocols, Humans, Radiology, Nuclear Medicine and imaging, Lymphoma, Large B-Cell, Diffuse, Mitoxantrone, Rituximab, Cyclophosphamide, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Aged, Etoposide, Retrospective Studies
Abstract

Advanced age is an independent poor prognostic factor of diffuse large B-cell lymphoma (DLBCL). PMitCEBO (mitoxantrone, cyclophosphamide, etoposide, vincristine, bleomycin, and prednisolone) is an alternative to the cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen to decrease side effects in elderly patients. Many studies have shown prognostic value of an interim FDG PET-CT to predict survival. A recent consensus (ICML, Lugano 2013) has suggested using the 5-point scale Deauville criteria instead of those of the International Harmonization Project (IHP) to visually assess the response on interim PET. The objective of this study was to evaluate the prognostic value of an interim FDG PET-CT in patients older than 60 with treated DLBCL and to compare IHP and 5-PS Deauville visual interpretation to predict survival.Forty-eight patients (mean age 73.2±5.2 years) treated by R-PMitCEBO for DLBCL undergoing FDG PET-CT before and after 3 cycles of treatment were retrospectively included. Event-free survival and overall survival were determined by Kaplan-Meier method and compared with interim PET-CT results using IHP and 5-PS Deauville criteria.Interim PET results using 5-PS Deauville criteria were significantly correlated with EFS (P0.0001) and OS (P=0.001) whereas they were moderately correlated with EFS (P=0.046) and not with OS (P=0.106) using IHP criteria. Two-year EFS and OS rates were 86.5% and 89.2%, respectively, for patients in 1-3 score group, and 27.3% and 36.4%, respectively, for patients in ≥4 score group using the Deauville criteria.Our results confirmed the prognostic value of an interim PET-CT in elderly patients with DLBCL and the better performance of the 5-PS Deauville criteria.

Published
2022

35. Can nivolumab alone cure patients with relapse or refractory Hodgkin lymphoma? A 5-year analysis of the French early access program (EPA)

Author

Manson, Guillaume, Herbaux, Charles, de Colella, Jean Marc Schiano, Casasnovas, René-Olivier, Stamatoullas, Aspasia, Deau, Benedicte, Schmitt, Anna, Regny, Caroline, Bouabdallah, Krimo, Chauchet, Adrien, Ghesquieres, Herve, Tempescul, Adrian, Dulery, Remy, Nicolas-Virelizier, Emmanuelle, Delmer, Alain, Borel, Cécile, Dercle, Laurent, Brice, Pauline, Houot, Roch, Chard-Hutchinson, Xavier, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Bergonié [Bordeaux], UNICANCER, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Léon Bérard [Lyon], Centre Hospitalier Universitaire de Reims (CHU Reims), 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), Columbia University Medical Center (CUMC), Columbia University [New York], Hopital Saint-Louis [AP-HP] (AP-HP), Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer (MOBIDIC), Université de Rennes (UR)-Etablissement français du sang [Rennes] (EFS Bretagne)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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] Life Sciences [q-bio], Antineoplastic Agents, Immunological, Nivolumab, [SDV]Life Sciences [q-bio], Chronic Disease, Humans, Hematology, Neoplasm Recurrence, Local, Hodgkin Disease, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2022
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38. Prognostic value of interim FDG PET-CT in patients older than 60 years with diffuse large B-cell lymphoma treated by PMitCEBO plus rituximab. Comparison between Deauville 5-point scale and International Harmonization Project criteria

Author

LOMBION, Naelle, primary, ROBIN, Philippe, additional, TEMPESCUL, Adrian, additional, LE ROUX, Pierre-Yves, additional, SCHICK, Ulrike, additional, GUILLERM, Gaëlle, additional, IANOTTO, Jean-Christophe, additional, BERTHOU, Christian, additional, SALAÜN, Pierre-Yves, additional, and ABGRAL, Ronan, additional

Published
2022
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39. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life-experience of the French Network

Author

Laurence, Schenone, Caroline, Houillier, Marie Laure, Tanguy, Sylvain, Choquet, Kossi, Agbetiafa, Hervé, Ghesquières, Gandhi, Damaj, Anna, Schmitt, Krimo, Bouabdallah, Guido, Ahle, Remy, Gressin, Jérôme, Cornillon, Roch, Houot, Jean-Pierre, Marolleau, Luc-Matthieu, Fornecker, Olivier, Chinot, Frédéric, Peyrade, Reda, Bouabdallah, Cécile, Moluçon-Chabrot, Emmanuel, Gyan, Adrien, Chauchet, Olivier, Casasnovas, Lucie, Oberic, Vincent, Delwail, Julie, Abraham, Virginie, Roland, Agathe, Waultier-Rascalou, Lise, Willems, Franck, Morschhauser, Michel, Fabbro, Renata, Ursu, Catherine, Thieblemont, Fabrice, Jardin, Adrian, Tempescul, Denis, Malaise, Valérie, Touitou, Lucia, Nichelli, Magali, Le Garff-Tavernier, Aurélie, Plessier, Philippe, Bourget, Caroline, Bonmati, Sophie, Wantz-Mézières, Quentin, Giordan, Véronique, Dorvaux, Cyril, Charron, Waliyde, Jabeur, Khê, Hoang-Xuan, Luc, Taillandier, Carole, Soussain, and Thomas, Gastinne

Subjects
Central Nervous System, Lymphoma, Hematopoietic Stem Cell Transplantation, Carmustine, Transplantation, Autologous, Central Nervous System Neoplasms, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols, Humans, Prospective Studies, Neoplasm Recurrence, Local, Busulfan, Cyclophosphamide, Thiotepa, Etoposide
Abstract

We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n = 147) or at relapse (n = 119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n = 64), thiotepa-busulfan (n = 24), BCNU-etoposide-cytarabine-melphalan (BEAM, n = 36) and thiotepa-busulfan-cyclophosphamide (n = 142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.

Published
2021

40. Gonadal Function Recovery in Patients With Advanced Hodgkin Lymphoma Treated With a PET-Adapted Regimen: Prospective Analysis of a Randomized Phase III Trial (AHL2011)

Author

Demeestere, Isabelle, primary, Racape, Judith, additional, Dechene, Julie, additional, Dupuis, Jehan, additional, Morschhauser, Franck, additional, De Wilde, Virginie, additional, Lazarovici, Julien, additional, Ghesquieres, Hervé, additional, Touati, Mohamed, additional, Sibon, David, additional, Alexis, Magda, additional, Gac, Anne-Claire, additional, Moatti, Hannah, additional, Virelizier, Emmanuelle, additional, Maisonneuve, Hervé, additional, Pranger, Delphine, additional, Houot, Roch, additional, Fornecker, Luc-Matthieu, additional, Tempescul, Adrian, additional, André, Marc, additional, and Casasnovas, René-Olivier, additional

Published
2021
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41. Intravenous high-dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: an LOC network study

Author

Gandhi Damaj, Khê Hoang-Xuan, Emmanuel Gyan, Marion Lam, Laurent Meyer, Magali Sampo, Anna Schmitt, Sylvain Choquet, Cécile Moluçon-Chabrot, Remy Gressin, Caroline Houillier, Adrien Chauchet, Jérôme Tamburini-Bonnefoy, Laurent Kodjikian, Marie-Laure Le Lez, Lucie Oberic, Roch Houot, Christelle Schneider, Sarra Gattoussi, Hélène Massé, Béatrice Cochener, Jean-Claude Quintyn, Nathalie Cassoux, Priscille Ollé, Karine Angioi-Duprez, Luc-Matthieu Fornecker, Carole Soussain, Jean-Pierre Marolleau, Guido Ahle, Marie-Pierre Moles, Christophe Chiquet, Claire Schwartz, Marie Blonski, Fabien Croisé, Valérie Touitou, Laurent Ballonzoli, Frédéric Mouriaux, Hervé Ghesquières, Bahram Bodaghi, Adrian Tempescul, Magali Le Garff-Tavernier, Emeline Tabouret, Eve Rousseau, Paul Franciane, Benjamin Jany, Antoine P. Brézin, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Institut Curie [Paris], Université de Paris (UP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), 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)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Institut Bergonié [Bordeaux], UNICANCER, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Bordeaux Pellegrin [Bordeaux], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ophtalmologie [Hôpital de la Timone - APMH], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital pasteur [Colmar], CHU Grenoble, 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), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Clermont-Ferrand, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Strasbourg, Institut de neurosciences translationnelles de Paris (NeurATRIS - IHU-A-ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), None, Université Paris Cité (UPCité), 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 ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), 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)-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), Chard-Hutchinson, Xavier, 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), 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)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), 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), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Adult, Male, medicine.medical_specialty, Antimetabolites, Antineoplastic, medicine.medical_treatment, Retinal Neoplasms, [SDV]Life Sciences [q-bio], Population, Disease, Systemic therapy, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Intraocular Lymphoma, Internal medicine, medicine, Humans, education, Aged, Aged, 80 and over, Chemotherapy, education.field_of_study, business.industry, Hematology, Middle Aged, Prognosis, High dose methotrexate, 3. Good health, [SDV] Life Sciences [q-bio], Methotrexate, Treatment Outcome, 030220 oncology & carcinogenesis, Toxicity, 030221 ophthalmology & optometry, Administration, Intravenous, Female, business, medicine.drug, Vitreoretinal lymphoma
Abstract

International audience; The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011-2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 41/59 (69%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.

Published
2021
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46. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial

Author

Margaret Macro, Andrew Ar Belch, Antoine Tinel, Nathalie Meuleman, Jean Yves Mary, Christian Rose, Paula Rodriguez-Otero, Philippe Moreau, Wenming Chen, Michel Attal, Marie Lorraine Chretien, William Renwick, Kihyun Kim, Meletios A. Dimopoulos, Eileen M Boyle, Xavier Leleu, Michael Sturniolo, Thierry Facon, Heinz Ludwig, Mara Silvia Monzini, Vanessa Houck, Elena Zamagni, Adrian Tempescul, Salomon Manier, Cyrille Hulin, Shien Guo, Mohamad Mohty, Bruno M. Costa, Facon T., Dimopoulos M.A., Meuleman N., Belch A., Mohty M., Chen W.-M., Kim K., Zamagni E., Rodriguez-Otero P., Renwick W., Rose C., Tempescul A., Boyle E., Manier S., Attal M., Moreau P., Macro M., Leleu X., Lorraine Chretien M., Ludwig H., Guo S., Sturniolo M., Tinel A., Silvia Monzini M., Costa B., Houck V., Hulin C., Yves Mary J., CIC CHU ( Lille)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, National and Kapodistrian University of Athens (NKUA), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Cross Cancer Institute [Edmonton, AB, Canada], Service d'immunologie et hématologies biologiques [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), Capital Medical University, Beijing, Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Azienda Ospedaliero-Universitaria, Universidad de Navarra [Pamplona] (UNAV), Western Health The University of Melbourne, Université catholique de Lille (UCL), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), 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), Hôpital Hôtel-Dieu de Nantes - Centre Hospitalier Universitaire de Nantes (Hôpital Hôtel-Dieu de Nantes - CHU de Nantes), Hôpital Universitaire de Caen, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Wilhelminenspital Vienna, Evidera, Celgene Corporation, Celgene International, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Michel, Geneviève, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), 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), and Wilhelminenspital Vienna = Wilhelminen Hospital

Subjects
0301 basic medicine, Male, Cancer Research, [SDV]Life Sciences [q-bio], Dexamethasone, 0302 clinical medicine, Clinical trials, Multiple myeloma, Antineoplastic Combined Chemotherapy Protocols, Stage (cooking), Lenalidomide, Melphalan, Aged, 80 and over, Frailty, Hematology, Middle Aged, 3. Good health, Thalidomide, [SDV] Life Sciences [q-bio], Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, Haematological diseases, Human, Adult, medicine.medical_specialty, FIRST (MM-020) trial, Frail Elderly, Newly diagnosed, Transplant ineligible, Anesthésiologie, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, In patient, Adverse effect, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, medicine.disease, Clinical trial, Cancérologie, 030104 developmental biology, Charlson comorbidity index, Prednisone, business, Hématologie
Abstract

Patients with multiple myeloma are generally older and vary in fitness levels, which may influence the clinical benefit of treatment. Patients from the large, phase 3 FIRST trial in newly diagnosed multiple myeloma (NDMM) were retrospectively investigated to determine outcomes based on frailty using scores for age, Charlson Comorbidity Index (CCI), and Eastern Cooperative Oncology Group performance status (ECOG PS), instead of the EQ-5D quality-of-life questionnaire, as previously reported. ECOG PS (n = 1618) was investigated in frailty groups: frail (49%) and nonfrail (51%). Frail patients experienced worse progression-free and overall survival vs nonfrail patients. Prognostic assessment was improved when combining frailty and International Staging System stage (I/II vs III). Frail patients had a higher risk of developing grade 3/4 treatment-emergent adverse events. Treatment effects observed in the FIRST trial were confirmed per frailty group and per frailty and ISS group. The use of this ECOG PS–containing frailty scale as a predictive measure of clinical outcomes in patients with transplant-ineligible NDMM is supported by data from the FIRST trial. This score, based on age, CCI, and ECOG PS, can be easily replicated and may help design future myeloma studies in frail or nonfrail elderly patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2019
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47. Gonadal Function Recovery in Patients With Advanced Hodgkin Lymphoma Treated With a PET-Adapted Regimen: Prospective Analysis of a Randomized Phase III Trial (AHL2011)

Author

Roch Houot, Emmanuelle Nicolas Virelizier, Jehan Dupuis, Magda Alexis, Virginie De Wilde, Luc-Matthieu Fornecker, Julien Lazarovici, Marc André, Franck Morschhauser, David Sibon, Judith Racapé, Hervé Ghesquières, Anne-Claire Gac, Delphine Pranger, Hannah Moatti, Isabelle Demeestere, Hervé Maisonneuve, Julie Dechene, Adrian Tempescul, René-Olivier Casasnovas, Mohamed Touati, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'hématologie

Subjects
Oncology, Adult, Anti-Mullerian Hormone, Male, Cancer Research, medicine.medical_specialty, endocrine system, Dacarbazine, Bleomycin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Testis, medicine, Humans, Doxorubicin, In patient, Prospective Studies, Etoposide, 030219 obstetrics & reproductive medicine, business.industry, Ovary, Recovery of Function, Hodgkin Disease, Vinblastine, Regimen, chemistry, ABVD, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Female, business, medicine.drug
Abstract

PURPOSE The prospective, randomized AHL2011 trial demonstrated that the use of the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (ABVD) after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) in early responders on the basis of a positron emission tomography (PET)–driven strategy was safe and minimized toxicity compared with standard 6 BEACOPPescalated cycles. This substudy investigated the benefit of this strategy in gonadal function and fertility in patients under 45 years old. METHODS Ovarian function was assessed by serum measurement of follicle-stimulating hormone (FSH), estradiol, and anti-müllerian hormone in women, and semen analysis, FSH, and testosterone levels were used to evaluate testicular function in men at baseline, end of treatment, and during 5 years of follow-up. RESULTS A total of 145 women and 424 men, enrolled between May 19, 2011, and April 29, 2014, were included. The risk of premature ovarian insufficiency (FSH > 24 IU/L) and of having a low ovarian reserve (anti-müllerian hormone < 0.5 ng/mL) was reduced after treatment in the PET-driven group (odds ratio [OR], 0.20; 95% CI, 0.08 to 0.50; P = .001 and OR, 0.15; 95% CI, 0.04 to 0.56, P = .005, respectively). Both parameters were correlated with age and dose of alkylating agents. However, no significant differences were observed in terms of pregnancy rates. Men in the PET-driven group had a higher recovery rate of sperm parameters after treatment compared with the standard BEACOPPescalated group, as well as a lower risk of severe testicular damage (OR, 0.26; 95% CI, 0.13 to 0.5; P < .0001) and a higher likelihood of achieving pregnancy (OR, 3.7; 95% CI, 1.4 to 9.3; P = .004). CONCLUSION Although both treatments affected ovarian reserve and spermatogenesis, the PET-driven strategy decreased the risk of gonadal dysfunction and infertility in advanced Hodgkin lymphoma.

Published
2021

48. Identification of altered cell signaling pathways using proteomic profiling in stable and progressive chronic lymphocytic leukemia

Author

Bagacean, Cristina, primary, Iuga, Cristina Adela, additional, Bordron, Anne, additional, Tempescul, Adrian, additional, Pralea, Ioana-Ecaterina, additional, Bernard, Delphine, additional, Cornen, Melanie, additional, Bergot, Tiffany, additional, Le Dantec, Christelle, additional, Brooks, Wesley, additional, Saad, Hussam, additional, Ianotto, Jean-Christophe, additional, Pers, Jacques-Olivier, additional, Zdrenghea, Mihnea, additional, Berthou, Christian, additional, and Renaudineau, Yves, additional

Published
2021
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50. Rapid and complete response to idelalisib in a case of Richter syndrome

Author

Bagacean, C, Zdrenghea, M, Saad, H, Berthou, C, Renaudineau, Y, Tempescul, A, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Université de Médicine et Pharmacie 'Iuliu Hatieganu', and Laboratoire d'Immunologie et Immunothérapie [Brest]

Subjects
immune system diseases, [SDV]Life Sciences [q-bio], hemic and lymphatic diseases, chronic lymphocytic leukemia, small lymphocytic lymphoma, Case Report, Richter syndrome, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, ComputingMilieux_MISCELLANEOUS, idelalisib
Abstract

Cristina Bagacean,1–3 Mihnea Zdrenghea,4 Hussam Saad,1 Christian Berthou,1,2 Yves Renaudineau,3 Adrian Tempescul1,2 1Department of Hematology, Brest University Medical School Hospital, Brest, France; 2U1227 B Lymphocytes and Autoimmunity, University of Brest, INSERM, IBSAM, Brest, France; 3Laboratory of Immunology and Immunotherapy, Brest University Medical School Hospital, Brest, France; 4Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania Abstract: Richter syndrome (RS) is an aggressive lymphoma arising on the back of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and is the most common B-cell malignancy in the Western world. In the majority of cases, RS presents an activated B cell (ABC) phenotype of diffuse large B-cell lymphoma (DLBCL). From the therapeutic point of view, selective inhibition of PI3Kδ with idelalisib represents a valuable addition to available treatment options for patients with CLL/SLL, many of whom do not respond to or cannot tolerate chemoimmunotherapy. However, to our knowledge, there have been no prospective studies evaluating idelalisib efficacy in a DLBCL-ABC form of RS. Here, we present a case of a DLBCL-ABC form of RS achieving a complete response at 3 weeks after initiating idelalisib and rituximab therapy for six cycles. This response was maintained during the idelalisib monotherapy, but the patient relapsed rapidly after treatment was withdrawn, because of a grade three immune colitis that developed at 10 months of treatment. This report demonstrates that idelalisib is highly effective in RS and provides an attractive option in this aggressive disease. This agent could meet an unmet need by providing a treatment option with a tolerable safety profile for elderly patients with RS. Keywords: chronic lymphocytic leukemia, small lymphocytic lymphoma, Richter syndrome, idelalisib

Published
2019

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