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1. Identification, risk factors, and clinical course of CNS relapse in DLBCL patients across 19 prospective phase 2 and 3 trials—a LYSA and GLA/ DSHNHL collaboration

Author

Frontzek, Fabian, Renaud, Loïc, Dührsen, Ulrich, Poeschel, Viola, Bernard, Sophie, Chartier, Loïc, Ketterer, Nicolas, Récher, Christian, Fitoussi, Olivier, Held, Gerhard, Casasnovas, Olivier, Haioun, Corinne, Mounier, Nicolas, Tilly, Hervé, Morschhauser, Franck, Le Gouill, Steven, Karsten, Imke E., Duns, Gerben, Steidl, Christian, Scott, David W., Klapper, Wolfram, Rosenwald, Andreas, Ott, German, Molina, Thierry, Lenz, Georg, Ziepert, Marita, Altmann, Bettina, Thieblemont, Catherine, and Schmitz, Norbert

Published
2024
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2. Central nervous system relapse in younger patients with diffuse large B-cell lymphoma: a LYSA and GLA/DSHNHL analysis

Author

Thieblemont, Catherine, Altmann, Bettina, Frontzek, Fabian, Renaud, Loïc, Chartier, Loic, Ketterer, Nicolas, Récher, Christian, Poeschel, Viola, Fitoussi, Olivier, Held, Gerhard, Casasnovas, Olivier, Haioun, Corinne, Morschhauser, Franck, Glass, Bertram, Mounier, Nicolas, Tilly, Herve, Rosenwald, Andreas, Ott, German, Lenz, Georg, Molina, Thierry, Ziepert, Marita, and Schmitz, Norbert

Published
2023
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3. Angioimmunoblastic T‐cell lymphoma and Kaposi sarcoma: A fortuitous collision?

Author

Poullot, Elsa, primary, Milowich, Dina, additional, Lemonnier, François, additional, Bisig, Bettina, additional, Robe, Cyrielle, additional, Pelletier, Laura, additional, Letourneau, Audrey, additional, Dupuy, Aurélie, additional, Sako, Nouhoum, additional, Ketterer, Nicolas, additional, Carde, Patrice, additional, Dartigues, Peggy, additional, Delfau‐Larue, Marie‐Hélène, additional, de Leval, Laurence, additional, and Gaulard, Philippe, additional

Published
2023
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4. Angioimmunoblastic T‐cell lymphoma and Kaposi sarcoma: A fortuitous collision?

Author

Poullot, Elsa, Milowich, Dina, Lemonnier, François, Bisig, Bettina, Robe, Cyrielle, Pelletier, Laura, Letourneau, Audrey, Dupuy, Aurélie, Sako, Nouhoum, Ketterer, Nicolas, Carde, Patrice, Dartigues, Peggy, Delfau‐Larue, Marie‐Hélène, de Leval, Laurence, and Gaulard, Philippe

Subjects
T-cell lymphoma, KAPOSI'S sarcoma, FOLLICULAR dendritic cells, T helper cells, NUCLEOTIDE sequencing, DISEASE relapse, OVARIAN follicle
Abstract

Aims: Follicular helper T‐cell (TFH) lymphoma of the angioimmunoblastic‐type (AITL), one of the most prevalent T‐cell lymphomas, typically encompasses proliferation of high endothelial venules and Epstein–Barr virus‐positive immunoblasts, but neither infection with HHV8 nor association with Kaposi's sarcoma (KS) have been described. The aims of this study are to characterise the association between AITL and HHV8 infection or KS. Methods and results: Three male patients aged 49–76 years, HIV‐negative, with concurrent nodal involvement by AITL and KS, were identified from our files and carefully studied. Two patients originated from countries where endemic KS occurs, including one with cutaneous KS. The lymphomas featured abundant vessels, expanded follicular dendritic cells and neoplastic TFH cells [PD1+ (three of three), ICOS+ (three of three), CXCL13+ (three of three), CD10+ (two of three), BCL6 (two of three)] but lacked EBV+ immunoblasts. The foci of KS consisted of subcapsular proliferations of ERG+, CD31+ and/or CD34+, HHV8+ spindle cells. High‐throughput sequencing showed AITL‐associated mutations in TET2 (three of three), RHOA (G17V) (three of three) and IDH2 (R172) (two of three), which were absent in the microdissected KS component in two cases. Relapses in two patients consisted of AITL, without evidence of KS. No evidence of HHV8 infection was found in a control group of 23 AITL cases. Conclusion: Concurrent nodal involvement by AITL and KS is rare and identification of both neoplastic components may pose diagnostic challenges. The question of whether the association between AITL and KS may be fortuitous or could reflect the underlying immune dysfunction in AITL remains open. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Supplementary Data from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author

Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary

Published
2023
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6. Table S5. Cohort variants. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author

Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary

Published
2023
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7. Table S2. Cell of origin according to MYD88 mutations. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author

Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary

Published
2023
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8. Table S7. Immunohistochemical markers and gene rearrangements according to MYD88 variants. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author

Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary

Published
2023
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9. Supplementary Data from Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study

Author

Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Mareschal, Sylvain, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Maingonnat, Catherine, primary, Jais, Jean-Philippe, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Molina, Thierry J., primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Brière, Josette, primary, Petrella, Tony, primary, Canioni, Danielle, primary, Fabiani, Bettina, primary, Coiffier, Bertrand, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, Bosly, André, primary, André, Marc, primary, Ketterer, Nicolas, primary, Salles, Gilles, primary, Tilly, Hervé, primary, Leroy, Karen, primary, and Jardin, Fabrice, primary

Published
2023
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10. Table S10. Clinical characteristics of patients with CNS relapse. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author

Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary

Published
2023
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11. Table S1. Clinical and immunohistochemical data according to MYD88 mutation status. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author

Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary

Published
2023
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12. Table S6. Cohort copy number variations. from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author

Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary

Published
2023
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13. Supplementary Figures from Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author

Dubois, Sydney, primary, Viailly, Pierre-Julien, primary, Bohers, Elodie, primary, Bertrand, Philippe, primary, Ruminy, Philippe, primary, Marchand, Vinciane, primary, Maingonnat, Catherine, primary, Mareschal, Sylvain, primary, Picquenot, Jean-Michel, primary, Penther, Dominique, primary, Jais, Jean-Philippe, primary, Tesson, Bruno, primary, Peyrouze, Pauline, primary, Figeac, Martin, primary, Desmots, Fabienne, primary, Fest, Thierry, primary, Haioun, Corinne, primary, Lamy, Thierry, primary, Copie-Bergman, Christiane, primary, Fabiani, Bettina, primary, Delarue, Richard, primary, Peyrade, Frédéric, primary, André, Marc, primary, Ketterer, Nicolas, primary, Leroy, Karen, primary, Salles, Gilles, primary, Molina, Thierry J., primary, Tilly, Hervé, primary, and Jardin, Fabrice, primary

Published
2023
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14. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study

Author

Copie-Bergman, Christiane, Cuillière-Dartigues, Peggy, Baia, Maryse, Briere, Josette, Delarue, Richard, Canioni, Danielle, Salles, Gilles, Parrens, Marie, Belhadj, Karim, Fabiani, Bettina, Recher, Christian, Petrella, Tony, Ketterer, Nicolas, Peyrade, Frederic, Haioun, Corinne, Nagel, Inga, Siebert, Reiner, Jardin, Fabrice, Leroy, Karen, Jais, Jean-Philippe, Tilly, Herve, Molina, Thierry Jo, and Gaulard, Philippe

Published
2015
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15. ALK-negative anaplastic large cell lymphoma with DUSP22 rearrangement has distinctive disease characteristics with better progression-free survival: a LYSA study

Author

Sibon, David, primary, Bisig, Bettina, additional, Bonnet, Christophe, additional, Poullot, Elsa, additional, Bachy, Emmanuel, additional, Cavalieri, Doriane, additional, Fataccioli, Virginie, additional, Bregnard, Cloe, additional, Drieux, Fanny, additional, Bruneau, Julie, additional, Lemonnier, Francois, additional, Dupuy, Aurelie, additional, Bossard, Celine, additional, Parrens, Marie, additional, Bouabdallah, Krimo, additional, Ketterer, Nicolas, additional, Berthod, Gregoire, additional, Cairoli, Anne, additional, Damaj, Gandhi, additional, Tournilhac, Olivier, additional, Jais, Jean-Philippe, additional, Gaulard, Philippe, additional, and De Leval, Laurence, additional

Published
2022
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16. Outcome of Patients with Primary Mediastinal Large B-Cell Lymphoma after R-CHOP21, R-CHOP14 and R-ACVBP: A Pooled Analysis of Clinical Trials from Lysa

Author

Sibon, David, primary, Gisselbrecht, Christian, additional, Molina, Thierry Jo, additional, Camus, Vincent, additional, Casasnovas, Olivier, additional, Recher, Christian, additional, Ketterer, Nicolas, additional, Fitoussi, Olivier, additional, Belhadj, Karim, additional, Bruneau, Julie, additional, Parrens, Marie, additional, Emile, Jean-François, additional, Briere, Josette, additional, Fabiani, Bettina, additional, Fest, Thierry, additional, Ghesquieres, Herve, additional, Morschhauser, Franck, additional, Haioun, Corinne, additional, Lamy, Thierry, additional, Hermine, Olivier, additional, Le Gouill, Steven, additional, and Jais, Jean-Philippe, additional

Published
2022
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17. Central nervous system relapse in younger patients with diffuse large B-cell lymphoma - a LYSA and GLA/ DSHNHL analysis

Author

Thieblemont, Catherine, primary, Altmann, Bettina, additional, Frontzek, Fabian, additional, Renaud, Loïc, additional, Chartier, Loic, additional, Ketterer, Nicolas, additional, Recher, Christian, additional, Poeschel, Viola, additional, Fitoussi, Olivier, additional, Held, Gerhard, additional, Casasnovas, René-Olivier, additional, Haioun, Corinne, additional, Morschhauser, Franck, additional, Glass, Bertram, additional, Mounier, Nicolas, additional, Tilly, Hervé, additional, Rosenwald, Andreas, additional, Ott, German, additional, Lenz, Georg, additional, Molina, Thierry, additional, Ziepert, Marita, additional, and Schmitz, Norbert, additional

Published
2022
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21. Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol

Author

Moreau, Philippe, Hullin, Cyrille, Garban, Frédéric, Yakoub-Agha, Ibrahim, Benboubker, Lotfi, Attal, Michel, Marit, Gérald, Fuzibet, Jean-Gabriel, Doyen, Chantal, Voillat, Laurent, Berthou, Christian, Ketterer, Nicolas, Casassus, Philippe, Monconduit, Mathieu, Michallet, Mauricette, Najman, Albert, Sotto, Jean-Jacques, Bataille, Régis, and Harousseau, Jean-Luc

Published
2006
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23. Updated recommendations for diagnosis and treatment of plasma cell myeloma in Switzerland

Author

Samaras, Panagiotis, primary, Bargetzi, Mario, additional, Betticher, Daniel C., additional, Driessen, Christoph, additional, Duchosal, Michel A., additional, Heim, Dominik, additional, Ketterer, Nicolas, additional, Lerch, Erika, additional, Matthes, Thomas, additional, Mey, Ulrich, additional, Pabst, Thomas, additional, Schmidt, Adrian, additional, Taverna, Christian, additional, Zander, Thilo, additional, and Renner, Christoph, additional

Published
2019
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26. Home care—a safe and attractive alternative to inpatient administration of intensive chemotherapies

Author

Lüthi, François, Fucina, Nadia, Divorne, Nathalie, Santos-Eggimann, Brigitte, Currat-Zweifel, Christine, Rollier, Patricia, Wasserfallen, Jean-Blaise, Ketterer, Nicolas, Leyvraz, Serge, Lüthi, François, Fucina, Nadia, Divorne, Nathalie, Santos-Eggimann, Brigitte, Currat-Zweifel, Christine, Rollier, Patricia, Wasserfallen, Jean-Blaise, Ketterer, Nicolas, and Leyvraz, Serge

Abstract

Objective: The objective of this study was to evaluate feasibility, safety, perception, and costs of home care for the administration of intensive chemotherapies. Methods: Patients receiving sequential chemotherapy in an inpatient setting, living within 30km of the hospital, and having a relative to care for them were offered home care treatment. Chemotherapy was administered by a portable, programmable pump via an implantable catheter. The main endpoints were safety, patient's quality of life [Functional Living Index—Cancer (FLIC)], satisfaction of patients and relatives, and costs. Results: Two hundred days of home care were analysed, representing a total of 46 treatment cycles of intensive chemotherapy in 17 patients. Two cycles were complicated by technical problems that required hospitalisation for a total of 5days. Three major medical complications (heart failure, angina pectoris, and major allergic reaction) could be managed at home. Grades 1 and 2 nausea and vomiting occurring in 36% of patients could be treated at home. FLIC scores remained constant throughout the study. All patients rated home care as very satisfactory or satisfactory. Patient benefits of home care included increased comfort and freedom. Relatives acknowledged better tolerance and less asthenia of the patient. Home care resulted in a 53% cost benefit compared to hospital treatment (€420 ± 120/day vs. €896 ± 165/day). Conclusion: Administration of intensive chemotherapy regimens at home was feasible and safe. Quality of life was not affected; satisfaction of patients and relatives was very high. A psychosocial benefit was observed for patients and relatives. Furthermore, a cost-benefit of home care compared to hospital treatment was demonstrated

Published
2018

27. Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis: a single-centre experience

Author

Frossard, Valérie, Ketterer, Nicolas, Rosselet, Anne, Meier, Pascal, Cairoli, Anne, Duchosal, Michel, Kovacsovics, Tibor, Frossard, Valérie, Ketterer, Nicolas, Rosselet, Anne, Meier, Pascal, Cairoli, Anne, Duchosal, Michel, and Kovacsovics, Tibor

Abstract

Primary systemic amyloidosis (AL amyloidosis) continues to have a very poor prognosis. Most therapeutic strategies remain unsatisfactory. Conventional chemotherapy is known to offer at best only moderate efficacy. Several studies have yielded higher complete response rates after high-dose chemotherapy and autologous stem cell transplantation (ASCT) in addition to improving outcomes in a subgroup of patients. However, the superiority of an intensive approach in AL amyloidosis has not been confirmed in a randomised trial. The precise role of ASCT remains unclear. We report our experience in 16 patients diagnosed with AL amyloidosis and treated in a multidisciplinary approach with high-dose melphalan and ASCT. Median age was 59 (39-71)years. The kidneys were predominantly affected in 75% of cases; two or more organs were affected in 38%. Median time from diagnosis to transplantation was 2 (1-4)months. Three patients (19%) developed acute renal failure and required transient dialysis. Transplant-related mortality was 6% after 100days. Haematological complete response (CR) was obtained in nine (56%) and organ response in six (38%) patients. Nine out of 12 patients (75%) with kidney involvement exhibited a sustained clinical benefit at 12months. Half of all the patients (n = 8) were alive after a median follow-up of 33months, including two in continuous CR. This suggests that high-dose chemotherapy and ASCT are still valid treatment options in AL amyloidosis and that a significant number of patients with renal involvement might benefit from this approach

Published
2018

29. Y(90) -Ibritumomab tiuxetan (Y(90) -IT) and high-dose melphalan as conditioning regimen before autologous stem cell transplantation for elderly patients with lymphoma in relapse or resistant to chemotherapy: a feasibility trial (SAKK 37/05)

Author

Ketterer, Nicolas, Bischof Delaloye, Angelika, Berardi Vilei, Simona, Wannesson, Luciano, Rentschler, Jochen, Jost, Lorenz, Pabst, Thomas, Voegeli, Michèle, Lerch, Erika, Rondeau, Stephanie, Ghielmini, Michele, and Bargetzi, Mario

Subjects
610 Medicine & health
Abstract

Standard conditioning regimens for autologous stem cell transplantation (ASCT) are often not tolerated by elderly patients, on one hand. Single high-dose melphalan, on the other hand, has been shown to be safe and active as a pretransplant preparative regimen in elderly patients. Y(90) -Ibritumomab tiuxetan (Y(90) -IT) is well tolerated and feasible in the transplantation setting. We therefore investigated the combination of high-dose melphalan and Y(90) -IT as a conditioning regimen for patients ≥65 years of age. Patients with relapsed or resistant CD20-positive lymphoma in remission after salvage chemotherapy could be enrolled. High-dose therapy consisted of standard dose Y(90) -IT (0.4-mCi/kg body weight) followed by melphalan at escalating doses (100, 140, 170 and 200 mg/m(2) ) and ASCT. The primary objective was to identify the maximum tolerated dose; secondary end points were complete response (CR) rate 100 days after transplantation and toxicity. Twenty patients (median age 72 years) were included. No DLT occurred at any dose level. Thirteen patients completed the treatment, 11 were evaluable for response. Seven patients did not complete treatment because of mobilization failure (n = 3), progressive disease (n = 2), worsening of cardiac function (n = 1), and grade 3 dyspnea (n = 1). Seven patients achieved a CR/complete remission/unconfirmed (CRu) and 2 had stable disease. Five out of 7 responding patients were still alive more than 3 years after transplantation. The 2 patients with SD had a long-term survival of 3 and 5 years, respectively. Nonhematological grade 3 or higher treatment related adverse events (AEs) were infection (n = 6), including 2 cases of febrile neutropenia, diarrhea (n = 3), mucositis, anorexia, viral hepatitis, hypokalemia, dehydration, and multiorgan failure (n = 1 for each). The combination of Y(90) -IT and high-dose melphalan is feasible before ASCT for elderly patients, with promising activity and manageable toxicity.

Published
2017
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30. Diagnosis-to-Treatment Interval Is an Important Clinical Factor in Newly Diagnosed Diffuse Large B-Cell Lymphoma and Has Implication for Bias in Clinical Trials

Author

Maurer, Matthew J., primary, Ghesquières, Hervé, additional, Link, Brian K., additional, Jais, Jean-Philippe, additional, Habermann, Thomas M., additional, Thompson, Carrie A., additional, Haioun, Corinne, additional, Allmer, Cristine, additional, Johnston, Patrick B., additional, Delarue, Richard, additional, Micallef, Ivana N., additional, Peyrade, Frederic, additional, Inwards, David J., additional, Ketterer, Nicolas, additional, Farooq, Umar, additional, Fitoussi, Olivier, additional, Macon, William R., additional, Molina, Thierry J., additional, Syrbu, Sergei, additional, Feldman, Andrew L., additional, Slager, Susan L., additional, Weiner, George J., additional, Ansell, Stephen M., additional, Cerhan, James R., additional, Salles, Gilles A., additional, Witzig, Thomas E., additional, Tilly, Hervé, additional, and Nowakowski, Grzegorz S., additional

Published
2018
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32. Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study

Author

Dubois , Sydney, Viailly , J., Mareschal , Sylvain, Bohers , Elodie, Bertrand , P., Ruminy , Philippe, Maingonnat , Catherine, Jais , Jean-Philippe, Peyrouze , Pauline, Figeac , Martin, Molina , Thierry, Desmots , Fabienne, Fest , Thierry, Haioun , Corinne, Lamy , Thierry, Copie-Bergman , Christiane, Briere , J., Petrella , Tony, Canioni , Danielle, Fabiani , Bettina, Coiffier , Bertrand, Delarue , Richard, Peyrade , Frédéric, Bosly , A., Andre , M., Ketterer , Nicolas, Salles , Gilles, Tilly , Hervé, Leroy , Karen, Jardin , Fabrice, Viailly , Pierre-Julien, Bertrand , Bertrand, Brière , Josette, André , André, André , Marc, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche des Cordeliers - Equipe 20 'ingénierie des connaissances en santé', Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-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 Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine Henri Warembourg - Université de Lille, Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Service d'anatomie pathologique [CHU Necker], Microenvironnement et cancer (MiCa), 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], Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hôpital Maisonneuve-Rosemont, Centre de référence des mastocytoses (CEREMAST), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hematologie, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'immuno-hématologie pédiatrique [CHU Necker], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Dinant-Godinne UCL Namur, Department of Oncology, Lausanne Hospital, Lausanne Hospital, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Service de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National du Cancer (INCA), 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 ), Jonchère, Laurent, Rouen Business School, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Lille 2 - Faculté de Médecine, Institut pour la recherche sur le cancer de Lille [Lille] ( IRCL ) -Université de Lille, Droit et Santé, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Maisonneuve-Rosemont Hospital Research Center, University of Montreal, Service de pathologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes ( LITIS ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Institut national des sciences appliquées Rouen Normandie ( INSA Rouen Normandie ), Normandie Université ( NU ), Unité de Taphonomie médico-légale ( UTML ), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -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 Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Microenvironnement et cancer ( MiCa ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de référence des mastocytoses, Service d'anatomie et cytologie pathologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Côte d'Azur (UCA)-UNICANCER, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (MGD) Service d'hématologie, Groupe d'étude des proliférations lymphoïdes, Université de Rouen - Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC) - École pratique des hautes études (EPHE) - Université Paris Diderot - Paris 7 (UPD7) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL) - Université de Lille, Droit et Santé, Université de Rennes 1 (UR1) - 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 ), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Hôpital Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) - Groupe Hospitalier Saint-Louis-Lariboisière- Fernand-Widal - Université Paris Diderot - Paris 7 (UPD7), Centre de pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) - AP-HP Hôpital Necker - Enfants Malades [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC) - Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Saint-Antoine [APHP], Service de Radio-Oncologie [Lyon], Hospices Civils de Lyon - Centre Hospitalier Lyon Sud [Pierre Bénite], Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - AP-HP Hôpital Necker - Enfants Malades [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10 - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Le Havre Normandie (ULH) - Université de Rouen - Institut National des Sciences Appliquées - Rouen (INSA Rouen), and Institut National des Sciences Appliquées (INSA) - Institut National des Sciences Appliquées (INSA)

Subjects
0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Cancer Research, Receptors, Cytoplasmic and Nuclear, Cell Cycle Proteins, TUMOR-SUPPRESSOR GENE, Genome, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, PROGNOSTIC-SIGNIFICANCE, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Molecular Targeted Therapy, Prospective Studies, Precision Medicine, Exome sequencing, Genetics, Oncogene Proteins, B-Lymphocytes, High-Throughput Nucleotide Sequencing, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, 3. Good health, DNA-Binding Proteins, GENOME, Phosphotransferases (Alcohol Group Acceptor), Oncology, Vincristine, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Lymphoma, Large B-Cell, Diffuse, medicine.drug, EXPRESSION, [SDV.IMM] Life Sciences [q-bio]/Immunology, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, FREQUENT, Biology, Karyopherins, DNA sequencing, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, TARGETS, Exome Sequencing, medicine, Humans, RITUXIMAB, Cyclophosphamide, Tumor Necrosis Factor alpha-Induced Protein 3, Gene Expression Profiling, CLASSICAL HODGKIN LYMPHOMA, SOMATIC MUTATIONS, Precision medicine, medicine.disease, Lymphoma, Gene expression profiling, 030104 developmental biology, Doxorubicin, GTP-Binding Protein alpha Subunits, Gq-G11, Prednisone, BURKITT-LYMPHOMA, Diffuse large B-cell lymphoma
Abstract

Purpose: Next-generation sequencing (NGS) has detailed the genomic characterization of diffuse large B-cell lymphoma (DLBCL) by identifying recurrent somatic mutations. We set out to design a clinically feasible NGS panel focusing on genes whose mutations hold potential therapeutic impact. Furthermore, for the first time, we evaluated the prognostic value of these mutations in prospective clinical trials. Experimental Design: A Lymphopanel was designed to identify mutations in 34 genes, selected according to literature and a whole exome sequencing study of relapsed/refractory DLBCL patients. The tumor DNA of 215 patients with CD20+de novo DLBCL in the prospective, multicenter, and randomized LNH-03B LYSA clinical trials was sequenced to deep, uniform coverage with the Lymphopanel. Cell-of-origin molecular classification was obtained through gene expression profiling with HGU133+2.0 Affymetrix GeneChip arrays. Results: The Lymphopanel was informative for 96% of patients. A clear depiction of DLBCL subtype molecular heterogeneity was uncovered with the Lymphopanel, confirming that activated B-cell–like (ABC), germinal center B-cell like (GCB), and primary mediastinal B-cell lymphoma (PMBL) are frequently affected by mutations in NF-κB, epigenetic, and JAK–STAT pathways, respectively. Novel truncating immunity pathway, ITPKB, MFHAS1, and XPO1 mutations were identified as highly enriched in PMBL. Notably, TNFAIP3 and GNA13 mutations in ABC patients treated with R-CHOP were associated with significantly less favorable prognoses. Conclusions: This study demonstrates the contribution of NGS with a consensus gene panel to personalized therapy in DLBCL, highlighting the molecular heterogeneity of subtypes and identifying somatic mutations with therapeutic and prognostic impact. Clin Cancer Res; 22(12); 2919–28. ©2016 AACR. See related commentary by Lim and Elenitoba-Johnson, p. 2829

Published
2016

33. FCGR3A/2A polymorphisms and Diffuse Large B-cell Lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1,134 patients from two prospective cohorts

Author

Ghesquières, Hervé, Larrabee, Beth R., Haioun, Corinne, Link, Brian K., Verney, Aurélie, Slager, Susan L., Ketterer, Nicolas, Ansell, Stephen M., Delarue, Richard, Maurer, Matthew J., Fitoussi, Olivier, Habermann, Thomas M., Peyrade, Fréderic, Dogan, Ahmet, Molina, Thierry J., Novak, Anne J., Tilly, Hervé, Cerhan, James R., and Salles, Gilles

Subjects
Cohort Studies, Male, Polymorphism, Genetic, Genotype, Receptors, IgG, Humans, Female, Immunotherapy, Lymphoma, Large B-Cell, Diffuse, Prospective Studies, Prognosis, Polymorphism, Single Nucleotide, Article
Abstract

Single nucleotide polymorphisms (SNPs) in FCγ-receptor genes FCGR3A (rs396991) and FCGR2A (rs1801274) influence the affinity of the Fc portion of anti-CD20 immunoglobulin G1 monoclonal antibody. Their roles in diffuse large B-cell lymphoma (DLBCL) treated with rituximab in combination with anthracycline-based chemotherapy remain controversial. To address this question, we genotyped FCGR2A and FCGR3A SNPs in two prospective DLBCL cohorts from Lymphoma Study Association trials (N = 554) and Iowa/Mayo Specialized Program Of Research Excellence (N = 580). Correlations with treatment response and hematological toxicity were assessed in Lymphoma Study Association. Correlation with event-free survival (EFS) and overall survival (OS) was performed in both cohorts, followed by a meta-analysis to increase power. Our study shows the absence of correlation between these SNPs and treatment response. Grades 3 and 4 febrile neutropenia during treatment was more frequently observed in FCGR3A VV (39%) than VF (29%) and FF (32%) carriers (p = 0.04). Our analysis for EFS and OS shows that FCGR3A was not associated with outcome. In a meta-analysis using an ordinal model, FCGR2A (per R allele) was associated with a better EFS (hazard ratio = 0.87; 95%CI, 0.76-0.99; p = 0.04) and OS (hazard ratio = 0.86; 95%CI, 0.73-1.00; p = 0.05) which was not altered after adjustment for the International Prognostic Index. Overall, our data demonstrate that patients with DLBCL with the low-affinity FCγRIIA RR had an unexpectedly better outcome than FCγRIIA H carriers. Whether rituximab efficacy is improved in FCγRIIA RR patients due a clearance reduction or other functions of FCγRIIA in DLBCL should be investigated (clinicaltrials.gov identifiers: NCT00135499, NTC00135499 NCT00140595, NCT00144807, NCT00144755, NCT01087424, and NCT00301821). Copyright © 2016 John WileySons, Ltd.

Published
2016

34. Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P–Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author

Dubois, Sydney, primary, Viailly, Pierre-Julien, additional, Bohers, Elodie, additional, Bertrand, Philippe, additional, Ruminy, Philippe, additional, Marchand, Vinciane, additional, Maingonnat, Catherine, additional, Mareschal, Sylvain, additional, Picquenot, Jean-Michel, additional, Penther, Dominique, additional, Jais, Jean-Philippe, additional, Tesson, Bruno, additional, Peyrouze, Pauline, additional, Figeac, Martin, additional, Desmots, Fabienne, additional, Fest, Thierry, additional, Haioun, Corinne, additional, Lamy, Thierry, additional, Copie-Bergman, Christiane, additional, Fabiani, Bettina, additional, Delarue, Richard, additional, Peyrade, Frédéric, additional, André, Marc, additional, Ketterer, Nicolas, additional, Leroy, Karen, additional, Salles, Gilles, additional, Molina, Thierry J., additional, Tilly, Hervé, additional, and Jardin, Fabrice, additional

Published
2017
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35. Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and Non-L265P Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases

Author

Dubois, Sydney, primary, Viailly, Pierre-Julien, additional, Bohers, Elodie, additional, Bertrand, Philippe, additional, Ruminy, Philippe, additional, Marchand, Vinciane, additional, Maingonnat, Catherine, additional, Mareschal, Sylvain, additional, Picquenot, Jean-Michel, additional, Penther, Dominique, additional, Jais, Jean-Philippe, additional, Tesson, Bruno, additional, Peyrouze, Pauline, additional, Figeac, Martin, additional, Desmots, Fabienne, additional, Fest, Thierry, additional, Haioun, Corinne, additional, Lamy, Thierry, additional, Copie-Bergman, Christiane, additional, Fabiani, Bettina, additional, Delarue, Richard, additional, Peyrade, Frédéric, additional, Andre, Marc, additional, Ketterer, Nicolas, additional, Leroy, Karen, additional, Salles, Gilles A., additional, Molina, Thierry Jo, additional, Tilly, Hervé, additional, and Jardin, Fabrice, additional

Published
2016
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36. Integrated Analysis of IGHV Gene Status, Cell-of-Origin Signature and Genomic Features in Diffuse Large B-Cell Lymphoma

Author

Etancelin, Pascaline, primary, Dubois, Sydney, additional, Viailly, Pierre-Julien, additional, Bohers, Elodie, additional, Bertrand, Philippe, additional, Ruminy, Philippe, additional, Maingonnat, Catherine, additional, Picquenot, Jean-Michel, additional, Mareschal, Sylvain, additional, Jais, Jean-Philippe, additional, Tesson, Bruno, additional, Peyrouze, Pauline, additional, Figeac, Martin, additional, Fest, Thierry, additional, Haioun, Corinne, additional, Lamy, Thierry, additional, Copie-Bergman, Christiane, additional, Fabiani, Bettina, additional, Delarue, Richard, additional, Peyrade, Frédéric, additional, Marc, André, additional, Ketterer, Nicolas, additional, Leroy, Karen, additional, Salles, Gilles A., additional, Molina, Thierry Jo, additional, Tilly, Hervé, additional, Stevenson, Freda K, additional, and Jardin, Fabrice, additional

Published
2016
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37. A Simplified IPI Including BCL2 Identifies IPI 3 Patients with Poor Prognosis - a GLA/ Dshnhl and Lysa Collaboration

Author

Ziepert, Marita, Altmann, Bettina, Poeschel, Viola, Cristinelli, Caterina, Chartier, Loïc, Ketterer, Nicolas, Recher, Christian, Fitoussi, Olivier, Held, Gerhard, Casasnovas, Olivier, Haioun, Corinne, Mounier, Nicolas, Tilly, Hervé, Morschhauser, Franck, Rosenwald, Andreas, Ott, German, Molina, Thierry Jo, Lenz, Georg, Thieblemont, Catherine, and Schmitz, Norbert

Abstract

Introduction:The original IPI remains valid to identify prognostic groups of DLBCL patients (pts) treated with R-CHOP (Ruppert et al. Blood 2020) and has been used to define eligibility for more than 20 studies randomizing pts between R-CHOP and R-CHOP + X, none of which except the Polarix study met its endpoint. One reason why some studies failed was the inclusion of IPI 2/3 pts equalizing the difference between standard and experimental arm although significant survival differences in pts with higher IPI were detected. Following the WHO-HAEM5 classification, determination of BCL2and MYCrearrangements is mandatory to diagnose DLBCL, NOS and HGBL- MYC/ BCL2. As surrogate markers, we included immunohistochemistry (IHC) for MYC and BCL2 into the IPI model hoping for a wider spread of survival curves and better selection of pts suitable for future clinical trials.

Published
2023
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38. Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study.

Author

UCL - (SLuc) Service d'hématologie, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, Van Den Neste, Eric, Schmitz, Norbert, Mounier, Nicolas, Gill, Devinder, Linch, David, Trněný, Marek, Milpied, Nicolas, Radford, John, Ketterer, Nicolas, Shpilberg, Ofer, Dührsen, Ulrich, Ma, David, Brière, Josette, Thieblemont, Catherine, Salles, Gilles, Moskowitz, Craig H, Glass, Bertram, Gisselbrecht, Christian, UCL - (SLuc) Service d'hématologie, UCL - SSS/DDUV/BCHM - Biochimie-Recherche métabolique, Van Den Neste, Eric, Schmitz, Norbert, Mounier, Nicolas, Gill, Devinder, Linch, David, Trněný, Marek, Milpied, Nicolas, Radford, John, Ketterer, Nicolas, Shpilberg, Ofer, Dührsen, Ulrich, Ma, David, Brière, Josette, Thieblemont, Catherine, Salles, Gilles, Moskowitz, Craig H, Glass, Bertram, and Gisselbrecht, Christian

Abstract

Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second-line treatment for relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, the strategy is less clear in patients who require third-line treatment. Updated outcomes of 203 patients who could not proceed to scheduled ASCT in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) are herein reviewed. In the intent-to-treat analysis, overall response rate to third-line chemotherapy was 39%, with 27% CR or CR unconfirmed, and 12% PR. Among the 203 patients, 64 (31.5%) were eventually transplanted (ASCT 56, allogeneic SCT 8). Median overall survival (OS) of the entire population was 4.4 months. OS was significantly improved in patients with lower tertiary International Prognostic Index (IPI), patients responding to third-line treatment and patients transplanted with a 1-year OS of 41.6% compared with 16.3% for the not transplanted (P<0.0001). In multivariate analysis, IPI at relapse (hazard ratio (HR) 2.409) and transplantation (HR 0.375) independently predicted OS. Third-line salvage chemotherapy can lead to response followed by transplantation and long-term survival in DLBCL patients. However, improvement of salvage efficacy is an urgent need with new drugs.

Published
2016

39. Quel futur pour les voitures autonomes en Suisse ?

Author

Ketterer, Nicolas and Ketterer, Nicolas

Abstract

Le but de ce travail est de donner une vision d’ensemble sur le monde très complexe des VAs (par la suite appelées VA). L’arrivée des VA provoquera des changements de paradigmes susceptibles de révolutionner nos habitudes, en matière de mobilité, mais pas seulement. Vingt-trois interviews ont été menés lors de la recherche d’informations afin de réunir les connaissances les plus complètes possible. Une attention particulière a été portée à la variété des domaines d’activité des répondants, afin de ne pas biaiser les résultats. La cartographie prospective, méthode créée par le professeur HES Thomas Gauthier et par l’Ingénieur de recherche en Text Analytics et Data Science Pierre-Alexandre Fonta, a été utilisée pour faire ressortir les grandes tendances ainsi que les facteurs jouant un rôle prépondérant dans l’évolution de ce nouveau marché. Cet outil est très puissant pour comprendre les systèmes complexes où le nombre de facteurs et leur interdépendance sont élevés, car il révèle au lecteur, l’organisation d’un réseau de données. Il a ainsi permis à cinq répondants et à moi-même, en nous inspirant de la méthode des scénarios de Michel Godet (Godet, 1983), d’imaginer plusieurs futurs possibles pour les VA en Suisse. L’analyse des conséquences de chaque scénario a mené à l’identification du futur, améliorant le plus la mobilité et le confort de vie des citoyens. Le côté stratégique de cette approche permet à ce travail de proposer un plan d’action visant à atteindre ce futur souhaitable. Ces méthodes utilisées dans ce rapport peuvent être reprises dans de nombreux travaux de stratégie ou de prospective. Ce travail apporte au travers de l’analyse du marché des VA, un apport de connaissances sur des procédés ayant fait leurs preuves.

Published
2016

40. Y90-Ibritumomab tiuxetan (Y90-IT) and high-dose melphalan as conditioning regimen before autologous stem cell transplantation for elderly patients with lymphoma in relapse or resistant to chemotherapy: a feasibility trial (SAKK 37/05)

Author

Voegeli, Michèle, primary, Rondeau, Stephanie, additional, Berardi Vilei, Simona, additional, Lerch, Erika, additional, Wannesson, Luciano, additional, Pabst, Thomas, additional, Rentschler, Jochen, additional, Bargetzi, Mario, additional, Jost, Lorenz, additional, Ketterer, Nicolas, additional, Bischof Delaloye, Angelika, additional, and Ghielmini, Michele, additional

Published
2016
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41. FCGR3A /2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts

Author

Ghesquières, Hervé, primary, Larrabee, Beth R., additional, Haioun, Corinne, additional, Link, Brian K., additional, Verney, Aurélie, additional, Slager, Susan L., additional, Ketterer, Nicolas, additional, Ansell, Stephen M., additional, Delarue, Richard, additional, Maurer, Matthew J., additional, Fitoussi, Olivier, additional, Habermann, Thomas M., additional, Peyrade, Fréderic, additional, Dogan, Ahmet, additional, Molina, Thierry J., additional, Novak, Anne J., additional, Tilly, Hervé, additional, Cerhan, James R., additional, and Salles, Gilles, additional

Published
2016
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42. Primary bone diffuse large B-cell lymphoma: a retrospective evaluation on 76 cases from French institutional and LYSA studies

Author

Pilorge, Sylvain, primary, Harel, Stephanie, additional, Ribrag, Vincent, additional, Larousserie, Frédérique, additional, Willems, Lise, additional, Franchi, Patricia, additional, Legoff, Marielle, additional, Biau, David, additional, Anract, Philippe, additional, Roux, Christian, additional, Blanc-Autran, Estelle, additional, Delarue, Richard, additional, Gisselbrecht, Christian, additional, Ketterer, Nicolas, additional, Recher, Christian, additional, Bonnet, Christophe, additional, Peyrade, Frederic, additional, Haioun, Corinne, additional, Tilly, Hervé, additional, Salles, Gilles, additional, Brice, Pauline, additional, Bouscary, Didier, additional, Deau, Bénédicte, additional, and Tamburini, Jerome, additional

Published
2016
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43. Current status and updated recommendations for diagnosis and treatment of plasma cell myeloma in Switzerland

Author

Samaras, Panagiotis, Bargetzi, Mario, Betticher, Daniel C, Duchosal, Michel A, Heim, Dominik, Hess, Urs, Ketterer, Nicolas, Lerch, Erika, Matthes, Thomas, Mey, Ulrich, Pabst, Thomas, Taverna, Christian, Zander, Thilo, Renner, Christoph, Samaras, Panagiotis, Bargetzi, Mario, Betticher, Daniel C, Duchosal, Michel A, Heim, Dominik, Hess, Urs, Ketterer, Nicolas, Lerch, Erika, Matthes, Thomas, Mey, Ulrich, Pabst, Thomas, Taverna, Christian, Zander, Thilo, and Renner, Christoph

Abstract

The availability of drugs such as thalidomide, bortezomib and lenalidomide changed the landscape in myeloma treatment and has extended the median survival up to 10 years with a substantial improvement in quality of life. This development prompted a Swiss expert panel to re-evaluate the current status and formulate updated clinical recommendations for the diagnosis and treatment of plasma cell myeloma. These recommendations should help clinicians in their decision making to achieve the best outcome based on currently available data.

Published
2015

44. Integrative Analysis of Diffuse Large B Cell Lymphoma Mutational Landscape: A Lysa Study

Author

Dubois, Sydney, primary, Tesson, Bruno, additional, Viailly, Pierre-Julien, additional, Molina, Thierry, additional, Copie-Bergman, Christiane, additional, Mareschal, Sylvain, additional, Bohers, Elodie, additional, Bertrand, Philippe, additional, Ruminy, Philippe, additional, Maingonnat, Catherine, additional, Jais, Jean-Philippe, additional, Peyrouze, Pauline, additional, Figeac, Martin, additional, Desmots, Fabienne, additional, Fest, Thierry, additional, Haioun, Corinne, additional, Lamy, Thierry, additional, Briere, Josette, additional, Petrella, Tony, additional, Canioni, Danielle, additional, Fabiani, Bettina, additional, Coiffier, Bertrand, additional, Delarue, Richard, additional, Peyrade, Frederic, additional, Bosly, André, additional, Andre, Marc, additional, Ketterer, Nicolas, additional, Salles, Gilles A., additional, Tilly, Hervé, additional, Leroy, Karen, additional, and Jardin, Fabrice, additional

Published
2015
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45. Outcomes in Diffuse Large B-Cell Lymphoma (DLBCL) Patients Relapsing after Autologous Stem Cell Transplantation (ASCT): An Analysis of Patients Included in the Coral Study

Author

Van Den Neste, Eric, primary, Schmitz, Norbert, additional, Mounier, Nicolas, additional, Gill, Devinder, additional, Trneny, Marek, additional, Milpied, Noel, additional, Radford, John A., additional, Ketterer, Nicolas, additional, Shpilberg, Ofer, additional, Dührsen, Ulrich, additional, Ma, David, additional, Briere, Josette, additional, Thieblemont, Catherine, additional, Salles, Gilles A., additional, Moskowitz, Craig, additional, Glass, Bertran, additional, and Gisselbrecht, Christian, additional

Published
2015
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46. FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts.

Author

Ghesquières, Hervé, Larrabee, Beth R., Haioun, Corinne, Link, Brian K., Verney, Aurélie, Slager, Susan L., Ketterer, Nicolas, Ansell, Stephen M., Delarue, Richard, Maurer, Matthew J., Fitoussi, Olivier, Habermann, Thomas M., Peyrade, Fréderic, Dogan, Ahmet, Molina, Thierry J., Novak, Anne J., Tilly, Hervé, Cerhan, James R., Salles, Gilles, and Ghesquières, Hervé

Abstract

Single nucleotide polymorphisms (SNPs) in FCγ-receptor genes FCGR3A (rs396991) and FCGR2A (rs1801274) influence the affinity of the Fc portion of anti-CD20 immunoglobulin G1 monoclonal antibody. Their roles in diffuse large B-cell lymphoma (DLBCL) treated with rituximab in combination with anthracycline-based chemotherapy remain controversial. To address this question, we genotyped FCGR2A and FCGR3A SNPs in two prospective DLBCL cohorts from Lymphoma Study Association trials (N = 554) and Iowa/Mayo Specialized Program Of Research Excellence (N = 580). Correlations with treatment response and hematological toxicity were assessed in Lymphoma Study Association. Correlation with event-free survival (EFS) and overall survival (OS) was performed in both cohorts, followed by a meta-analysis to increase power. Our study shows the absence of correlation between these SNPs and treatment response. Grades 3 and 4 febrile neutropenia during treatment was more frequently observed in FCGR3A VV (39%) than VF (29%) and FF (32%) carriers (p = 0.04). Our analysis for EFS and OS shows that FCGR3A was not associated with outcome. In a meta-analysis using an ordinal model, FCGR2A (per R allele) was associated with a better EFS (hazard ratio = 0.87; 95%CI, 0.76-0.99; p = 0.04) and OS (hazard ratio = 0.86; 95%CI, 0.73-1.00; p = 0.05) which was not altered after adjustment for the International Prognostic Index. Overall, our data demonstrate that patients with DLBCL with the low-affinity FCγRIIA RR had an unexpectedly better outcome than FCγRIIA H carriers. Whether rituximab efficacy is improved in FCγRIIA RR patients due a clearance reduction or other functions of FCγRIIA in DLBCL should be investigated (clinicaltrials.gov identifiers: NCT00135499, NTC00135499 NCT00140595, NCT00144807, NCT00144755, NCT01087424, and NCT00301821). Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Published
2017
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47. Y90 -Ibritumomab tiuxetan (Y90 -IT) and high-dose melphalan as conditioning regimen before autologous stem cell transplantation for elderly patients with lymphoma in relapse or resistant to chemotherapy: a feasibility trial (SAKK 37/05).

Author

Voegeli, Michèle, Rondeau, Stephanie, Berardi Vilei, Simona, Lerch, Erika, Wannesson, Luciano, Pabst, Thomas, Rentschler, Jochen, Bargetzi, Mario, Jost, Lorenz, Ketterer, Nicolas, Bischof Delaloye, Angelika, and Ghielmini, Michele

Abstract

Standard conditioning regimens for autologous stem cell transplantation (ASCT) are often not tolerated by elderly patients, on one hand. Single high-dose melphalan, on the other hand, has been shown to be safe and active as a pretransplant preparative regimen in elderly patients. Y90 -Ibritumomab tiuxetan (Y90 -IT) is well tolerated and feasible in the transplantation setting. We therefore investigated the combination of high-dose melphalan and Y90 -IT as a conditioning regimen for patients ≥65 years of age. Patients with relapsed or resistant CD20-positive lymphoma in remission after salvage chemotherapy could be enrolled. High-dose therapy consisted of standard dose Y90 -IT (0.4-mCi/kg body weight) followed by melphalan at escalating doses (100, 140, 170 and 200 mg/m2 ) and ASCT. The primary objective was to identify the maximum tolerated dose; secondary end points were complete response (CR) rate 100 days after transplantation and toxicity. Twenty patients (median age 72 years) were included. No DLT occurred at any dose level. Thirteen patients completed the treatment, 11 were evaluable for response. Seven patients did not complete treatment because of mobilization failure (n = 3), progressive disease (n = 2), worsening of cardiac function (n = 1), and grade 3 dyspnea (n = 1). Seven patients achieved a CR/complete remission/unconfirmed (CRu) and 2 had stable disease. Five out of 7 responding patients were still alive more than 3 years after transplantation. The 2 patients with SD had a long-term survival of 3 and 5 years, respectively. Nonhematological grade 3 or higher treatment related adverse events (AEs) were infection (n = 6), including 2 cases of febrile neutropenia, diarrhea (n = 3), mucositis, anorexia, viral hepatitis, hypokalemia, dehydration, and multiorgan failure (n = 1 for each). The combination of Y90 -IT and high-dose melphalan is feasible before ASCT for elderly patients, with promising activity and manageable toxicity. [ABSTRACT FROM AUTHOR]

Published
2017
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48. Fertility preservation in cancer patients. Review of the French speaking part of Switzerland and recommendations for different situations

Author

Wunder, Dorothea, Perey, Lucien, Achtari, Chahin, Ambrosetti-jenny, Alexandra, Bellavia, Marina, Delaloye, Jean-François, De Ziegler, Dominique, Helg, Claudine, Ketterer, Nicolas, Petignat, Patrick, Primi, Marie-Pierre, Rosselet-Christ, Anne, Zaman, Khurshid, Réseau romand cancer et fertilité, and Gumy Pause, Fabienne

Subjects
Cryopreservation, Male, ddc:618, Cryopreservation/methods, Neoplasms/drug therapy/radiotherapy, Radiotherapy, Fertility Preservation, Antineoplastic Agents, Antineoplastic Agents/adverse effects, Medical Oncology, Radiotherapy/adverse effects, Fertility Preservation/methods, Infertility/chemically induced, Infertility, Neoplasms, Humans, Female, France, Switzerland, Language
Abstract

Due to constant progress in oncology, survival rates of patients (children and adults) with cancer are increasing. Consequently, the reproductive future of young cancer patients needs to be addressed carefully. Fertility preservation techniques are available and issues such as the time available for fertility treatments, patients' age, presence of a partner and patients' personal wishes have to be considered. In Switzerland, a first therapeutic network (Réseau Romand de Cancer et Fertilité), was created in the French speaking part of Switzerland in 2006. Since 2010, a global Swiss network (FertiSave) has been created. The goal of these networks is to maximise the safety and efficacy of fertility preservation options offered to cancer patients without compromising their oncological prognosis. Patients' needs have to be identified, the therapeutic options evaluated rapidly and the optimal treatment promptly implemented in these urgent situations. This article reviews the fertility preservation options currently available and makes recommendations for different specific cancer situations, consistent with the latest scientific evidence and in general agreement with international recommendations.

Published
2012

49. Current multiple myeloma treatment strategies with novel agents: a European perspective

Author

Ludwig, Heinz, Beksac, Meral, Blade, Joan, Boccadoro, Mario, Cavenagh, Jamie, Cavo, Michele, Dimopoulos, Meletios, Drach, Johannes, Einsele, Hermann, Facon, Thierry, Goldschmidt, Hartmut, Harousseau, Jean-Luc, Hess, Urs, Ketterer, Nicolas, Kropff, Martin, Mendeleeva, Larisa, Morgan, Gareth, Palumbo, Antonio, Plesner, Torben, San Miguel, Jesus, Shpilberg, Ofer, Sondergeld, Pia, Sonneveld, Pieter, and Zweegman, Sonja

Subjects
Multiple Myeloma, Thalidomide, Bortezomib, Lenalidomide, Stem-Cell Transplantation, Lenalidomide Plus Dexamethasone, Newly-Diagnosed Myeloma, Velcade-Thalidomide-Dexamethasone, Bone-Marrow-Transplantation, Randomized Controlled-Trial, Progression-Free Survival, Impaired Renal-Function, High Response Rates, Long-Term Survival
Abstract

The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents.

Published
2010

50. Current multiple myeloma treatment strategies with novel agents: a European perspective

Author

Ludwig, Heinz Beksac, Meral Blade, Joan Boccadoro, Mario and Cavenagh, Jamie Cavo, Michele Dimopoulos, Meletios Drach, Johannes Einsele, Hermann Facon, Thierry Goldschmidt, Hartmut Harousseau, Jean-Luc Hess, Urs Ketterer, Nicolas and Kropff, Martin Mendeleeva, Larisa Morgan, Gareth Palumbo, Antonio Plesner, Torben San Miguel, Jesus Shpilberg, Ofer and Sondergeld, Pia Sonneveld, Pieter Zweegman, Sonja

Subjects
Health Sciences, Επιστήμες Υγείας
Abstract

The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents. The Oncologist 2010; 15: 6-25

Published
2010

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