101 results on '"Nicolas Ketterer"'
Search Results
2. Updated recommendations for diagnosis and treatment of plasma cell myeloma in Switzerland
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Panagiotis Samaras, Mario Bargetzi, Daniel C. Betticher, Christoph Driessen, Michel A. Duchosal, Dominik Heim, Nicolas Ketterer, Erika Lerch, Thomas Matthes, Ulrich Mey, Thomas Pabst, Adrian Schmidt, Christian Taverna, Thilo Zander, and Christoph Renner
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IMIDs ,monoclonal antibodies ,multiple myeloma ,plasma cell myeloma ,proteasome inhibitors ,stem cell transplantation ,Medicine - Abstract
This update on plasma cell myeloma has been elaborated by a Swiss expert panel as a result of the plethora of new data on the treatment of plasma cell myeloma reported recently. It adds new insights to the more extensive review that was published 3 years ago and may help clinicians on decision making for their patients. The new recommendations for distinguishing plasma cell myeloma from smouldering myeloma are briefly presented, including a section on contemporary imaging studies with this respect. Former panel recommendations that remain unchanged by new results will not be discussed in detail as the major focus of this review is on treatment-relevant new developments.
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- 2019
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3. Current status and updated recommendations for diagnosis and treatment of plasma cell myeloma in Switzerland
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Panagiotis Samaras, Mario Bargetzi, Daniel Betticher, Michel Duchosal, Dominik Heim, Urs Hess, Nicolas Ketterer, Erika Lerch, Thomas Matthes, Ulrich Mey, Thomas Pabst, Christian Taverna, Thilo Zander, and Christoph Renner
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multiple myeloma ,Bortezomib ,stem cell transplantation ,lenalidomide ,relapsed/refractory ,Medicine - 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.
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- 2015
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4. A multicenter phase II trial (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma
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Christoph Renner, Pier Luigi Zinzani, Rémy Gressin, Dirk Klingbiel, Pierre-Yves Dietrich, Felicitas Hitz, Mario Bargetzi, Walter Mingrone, Giovanni Martinelli, Andreas Trojan, Krimo Bouabdallah, Andreas Lohri, Emmanuel Gyan, Christine Biaggi, Sergio Cogliatti, Francesco Bertoni, Michele Ghielmini, Peter Brauchli, and Nicolas Ketterer
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Background Mantle cell lymphoma accounts for 6% of all B-cell lymphomas and is generally incurable. It is characterized by the translocation t(11;14) leading to cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin threonine kinase and can be effectively blocked by mammalian target of rapamycin inhibitors. We set out to examine the single agent activity of the orally available mammalian target of rapamycin inhibitor everolimus in a prospective, multicenter trial in patients with relapsed or refractory mantle cell lymphoma (NCT00516412).Design and Methods Eligible patients who had received a maximum of three prior lines of chemotherapy were given everolimus 10 mg for 28 days (one cycle) for a total of six cycles or until disease progression. The primary endpoint was the best objective response. Adverse reactions, progression-free survival and molecular response were secondary endpoints.Results Thirty-six patients (35 evaluable) were enrolled and treatment was generally well tolerated with Common Terminology Criteria grade ≥3 adverse events (>5%) including anemia (11%), thrombocytopenia (11%) and neutropenia (8%). The overall response rate was 20% (95% CI: 8–37%) with two complete remissions and five partial responses; 49% of the patients had stable disease. At a median follow-up of 6 months, the median progression-free survival was 5.5 months (95% CI: 2.8–8.2) overall and 17.0 (6.4–23.3) months for 18 patients who received six or more cycles of treatment. Three patients achieved a lasting complete molecular response, as assessed by polymerase chain reaction analysis of peripheral blood.Conclusions Everolimus as a single agent is well tolerated and has anti-lymphoma activity in relapsed or refractory mantle cell lymphoma. Further studies of everolimus in combination with chemotherapy or as a single agent for maintenance treatment are warranted. (Clinicaltrials.gov identifier: NCT00516412)
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- 2012
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5. 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
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David Sibon, Christian Gisselbrecht, Thierry Jo Molina, Vincent Camus, Olivier Casasnovas, Christian Recher, Nicolas Ketterer, Olivier Fitoussi, Karim Belhadj, Julie Bruneau, Marie Parrens, Jean-François Emile, Josette Briere, Bettina Fabiani, Thierry Fest, Herve Ghesquieres, Franck Morschhauser, Corinne Haioun, Thierry Lamy, Olivier Hermine, Steven Le Gouill, and Jean-Philippe Jais
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
6. Supplementary Data from Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study
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Fabrice Jardin, Karen Leroy, Hervé Tilly, Gilles Salles, Nicolas Ketterer, Marc André, André Bosly, Frédéric Peyrade, Richard Delarue, Bertrand Coiffier, Bettina Fabiani, Danielle Canioni, Tony Petrella, Josette Brière, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Thierry J. Molina, Martin Figeac, Pauline Peyrouze, Jean-Philippe Jais, Catherine Maingonnat, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Sylvain Mareschal, Pierre-Julien Viailly, and Sydney Dubois
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Supplementary methods, figures, and tables Figure S1: Variant filters applied to Lymphopanel NGS data. Figure S2: Validation of variants according to SIFT and CADD scores. Figure S3: PMBL samples harbor more mutations than other DLBCL subtypes. Figure S4: Role of AID-induced SHM in DLBCL. Figure S5: Mutation frequency by subtype. Figure S6: Clustering of gene mutations according to subtype. Figure S7: Protein representations of observed mutations. Figure S8: Correlations between age and specific gene mutations. Figure S9: Prognosis according to IPI and subtype. Figure S10: Prognostic impact of gene mutations among the Lymphopanel. Table S1: Clinical characteristics of patients in our cohort. Table S2: Overview of the Lymphopanel used for NGS analysis. Table S3: Overview of pathway selection Table S4: Validation of variant filtering by an independent study of seven non-tumoral samples from DLBCL patients Table S5: Validated variants. Table S6: Lymphopanel NGS detection of genes with high AID target frequencies. Table S7: Prognostic impact of mutations in Lymphopanel genes
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- 2023
7. 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
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Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
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Supplementary Figures 1-10 Figure S1. MYD88 mutation VAF according to L265P or non-L265P variants. Figure S2. Age according to MYD88 mutation status and variant among ABC patients. Figure S3. Genomic profiles of DLBCL according to the presence of MYD88 L265P or non-L265P variants. Figure S4. Relative L265P allele expression level according to L265P VAF. Figure S5. Gene expression according to MYD88 status. Figure S6. NFkB pathway gene expression according to MYD88 mutational status. Figure S7. LPS score according to subtype and downstream NFkB alterations. Figure S8. Clustering according to expression levels of 27 genes involved in LPS response and differentially expressed according to MYD88 L265P. Figure S9. TNFAIP3 and CARD11 expression according to their copy number status. Figure S10. Additional survival analyses.
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- 2023
8. 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
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Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
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Clinical characteristics of the 17 patients with CNS relapse are provided, included time to CNS relapse, first-line treatment and response after first-line treatment. CR, Complete Response; PR, Partial Response; PD, Progressive Disease.
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- 2023
9. Data from Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study
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Fabrice Jardin, Karen Leroy, Hervé Tilly, Gilles Salles, Nicolas Ketterer, Marc André, André Bosly, Frédéric Peyrade, Richard Delarue, Bertrand Coiffier, Bettina Fabiani, Danielle Canioni, Tony Petrella, Josette Brière, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Thierry J. Molina, Martin Figeac, Pauline Peyrouze, Jean-Philippe Jais, Catherine Maingonnat, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Sylvain Mareschal, Pierre-Julien Viailly, and Sydney Dubois
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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
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- 2023
10. 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
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Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
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All relevant clinical data is included. Immunohistochemical results for BCL2, CD10, BCL6, MUM1, FOXP1, IgM and MYC are transcribed: 0 indicates negativity and 1 indicates positivity. For BCL2 and MYC, positivity is according to a threshold of 50% or 40% respectively.
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- 2023
11. 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
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Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
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Purpose: MYD88 mutations, notably the recurrent gain-of-function L265P variant, are a distinguishing feature of activated B-cell like (ABC) diffuse large B-cell lymphoma (DLBCL), leading to constitutive NFκB pathway activation. The aim of this study was to examine the distinct genomic profiles of MYD88-mutant DLBCL, notably according to the presence of the L265P or other non-L265P MYD88 variants.Experimental Design: A cohort of 361 DLBCL cases (94 MYD88 mutant and 267 MYD88 wild-type) was submitted to next-generation sequencing (NGS) focusing on 34 genes to analyze associated mutations and copy number variations, as well as gene expression profiling, and clinical and prognostic analyses.Results: Importantly, we highlighted different genomic profiles for MYD88 L265P and MYD88 non-L265P–mutant DLBCL, shedding light on their divergent backgrounds. Clustering analysis also segregated subgroups according to associated genetic alterations among patients with the same MYD88 mutation. We showed that associated CD79B and MYD88 L265P mutations act synergistically to increase NFκB pathway activation, although the majority of MYD88 L265P–mutant cases harbors downstream NFκB alterations, which can predict BTK inhibitor resistance. Finally, although the MYD88 L265P variant was not an independent prognostic factor in ABC DLBCL, associated CD79B mutations significantly improved the survival of MYD88 L265P–mutant ABC DLBCL in our cohort.Conclusions: This study highlights the relative heterogeneity of MYD88-mutant DLBCL, adding to the field's knowledge of the theranostic importance of MYD88 mutations, but also of associated alterations, emphasizing the usefulness of genomic profiling to best stratify patients for targeted therapy. Clin Cancer Res; 23(9); 2232–44. ©2016 AACR.
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- 2023
12. 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
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Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
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Supplementary methods, supplementary figure & table legends, and supplementary tables 3, 4, 8 & 9. Table S3: Overview of the Lymphopanel used for NGS analysis. Table S4: Overview of pathway selection Table S8. Genes involved in the LPS score. Table S9. Expression levels of genes involved in response to LPS stimulation according to MYD88 L265P.
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- 2023
13. 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
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Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
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Statistically significant differences (p
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- 2023
14. 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
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Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
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This table presents all variants identified among our cohort by Lymphopanel NGS. Variant type and variant allele frequency (VAF) are indicated.
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- 2023
15. 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
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Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
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This table presents all CNVs identified among our cohort using the ONCOCNV software. Duplication was considered when copy number was superior to 2 and deletion was considered when copy number was inferior to 2. False discovery rate (FDR) cutoff was set at 0.01.
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- 2023
16. 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
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Fabrice Jardin, Hervé Tilly, Thierry J. Molina, Gilles Salles, Karen Leroy, Nicolas Ketterer, Marc André, Frédéric Peyrade, Richard Delarue, Bettina Fabiani, Christiane Copie-Bergman, Thierry Lamy, Corinne Haioun, Thierry Fest, Fabienne Desmots, Martin Figeac, Pauline Peyrouze, Bruno Tesson, Jean-Philippe Jais, Dominique Penther, Jean-Michel Picquenot, Sylvain Mareschal, Catherine Maingonnat, Vinciane Marchand, Philippe Ruminy, Philippe Bertrand, Elodie Bohers, Pierre-Julien Viailly, and Sydney Dubois
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COO information according to the three techniques used in this study is given according to the various MYD88 variants present in our cohort.
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- 2023
17. Central nervous system relapse in younger patients with diffuse large B-cell lymphoma - a LYSA and GLA/ DSHNHL analysis
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Catherine Thieblemont, Bettina Altmann, Fabian Frontzek, Loïc Renaud, Loic Chartier, Nicolas Ketterer, Christian Recher, Viola Poeschel, Olivier Fitoussi, Gerhard Held, René-Olivier Casasnovas, Corinne Haioun, Franck Morschhauser, Bertram Glass, Nicolas Mounier, Hervé Tilly, Andreas Rosenwald, German Ott, Georg Lenz, Thierry Molina, Marita Ziepert, and Norbert Schmitz
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Hematology - Abstract
The majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with immunochemotherapy comprising rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients suffering progression or relapse in the central nervous system (CNS) face dismal outcomes. The impact of more aggressive regimens used in front-line therapy has not systematically been investigated in this context. To this end, we analyzed a large cohort of 2203 younger DLBCL patients treated on ten German and French prospective phase II and III trials following first-line therapy with R-CHOP, R-CHOEP (R-CHOP + etoposide), dose-escalated R-CHOEP followed by repetitive stem cell transplantation (R-MegaCHOEP), or rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycine, prednisone (R-ACVBP) followed by consolidation including multiple drugs crossing the blood-brain-barrier (BBB). DLBCL patients with age-adjusted International Prognostic Index (aaIPI) of 0–1 showed very low cumulative incidence (CI) rates of CNS relapse regardless of first-line therapy and CNS prophylaxis (3-year CI 0% − 1%). Younger high-risk patients with aaIPI of 2–3 had 3-year CI rates of 1.6% and 4% after R-ACVBP plus consolidation or R-(Mega)CHO(E)P, respectively (Hazard Ratio 2.4 (95% confidence interval: 0.8–7.4), p = 0.118). Thus, for younger high-risk patients, front-line regimens incorporating multiple agents crossing the BBB may reduce often fatal CNS relapse.
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- 2022
18. 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
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Richard Delarue, Frederic Peyrade, Matthew J. Maurer, Cristine Allmer, Gilles Salles, Thomas M. Habermann, Grzegorz S. Nowakowski, Corinne Haioun, Nicolas Ketterer, Umar Farooq, Patrick B. Johnston, Carrie A. Thompson, Olivier Fitoussi, Thomas E. Witzig, Jean-Philippe Jais, James R. Cerhan, Andrew L. Feldman, Ivana N. Micallef, David J. Inwards, George J. Weiner, Stephen M. Ansell, William R. Macon, Brian K. Link, Sergei Syrbu, Hervé Ghesquières, Hervé Tilly, Thierry Jo Molina, and Susan L. Slager
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Adolescent ,Population ,Kaplan-Meier Estimate ,Time-to-Treatment ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,Internal medicine ,medicine ,Humans ,Anthracyclines ,Prospective Studies ,education ,Prospective cohort study ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Odds ratio ,Middle Aged ,Prognosis ,medicine.disease ,Clinical trial ,Oncology ,B symptoms ,030220 oncology & carcinogenesis ,Cohort ,Disease Progression ,Female ,Immunotherapy ,Lymphoma, Large B-Cell, Diffuse ,medicine.symptom ,business ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
Purpose Selection bias in clinical trials has consequences for scientific validity and applicability of study results to the general population. There is concern that patients with clinically aggressive disease may not have enrolled in recent diffuse large B-cell lymphoma (DLBCL) trials due to the consent process and the inability to delay therapy for eligibility evaluation. We have examined the diagnosis-to-treatment interval (DTI) and its association with clinical factors and outcome in a clinic-based observational cohort of patients with DLBCL from the United States. Validation of results was performed in an independent, clinical trial-based cohort from Europe. Patients and Methods Patients were prospectively enrolled in the University of Iowa and Mayo Clinic Specialized Programs of Research Excellence Molecular Epidemiology Resource (MER; N = 986) or the Lymphoma Study Association (LYSA) LNH-2003 clinical trials program (N = 1,444). All patients received anthracycline-based immunochemotherapy at initial diagnosis. Associations of DTI with clinical factors and outcome were examined. Outcome was assessed using event-free survival at 24 months from diagnosis (EFS24). Results Median (range) DTI was 15 days (0 to 155 days in the MER and 23 days (0 to 215 days) in LYSA. Shorter DTI was strongly associated with adverse clinical factors, including elevated lactate dehydrogenase levels, poor performance status, B symptoms, and higher International Prognostic Index in both cohorts (all P < .001). Longer DTI was associated with improved EFS24 in both the MER (per-week odds ratio, 0.80; 95% CI, 0.74 to .0.87) and LYSA (per-week odds ratio, 0.90; 95% CI, 0.86 to 0.94); association with EFS24 remained significant after adjustment for International Prognostic Index. Conclusion DTI is strongly associated with prognostic clinical factors and outcome in newly diagnosed DLBCL. DTI should be reported in all clinical trials of newly diagnosed DLBCL and future trials should take steps to avoid selection bias due to treatment delay.
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- 2018
19. 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)
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Erika Lerch, Michele Ghielmini, Jochen Rentschler, Thomas Pabst, Lorenz M. Jost, Stephanie Rondeau, Simona Berardi Vilei, Mario Bargetzi, Luciano Wannesson, Angelika Bischof Delaloye, Michèle Voegeli, and Nicolas Ketterer
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Melphalan ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Ibritumomab tiuxetan ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,Internal medicine ,medicine ,Mucositis ,Chemotherapy ,business.industry ,Hematology ,General Medicine ,medicine.disease ,Surgery ,Transplantation ,Oncology ,030220 oncology & carcinogenesis ,business ,Progressive disease ,Febrile neutropenia ,030215 immunology ,medicine.drug - 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.
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- 2016
20. FCGR3A /2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts
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Hervé Tilly, Beth R. Larrabee, Frederic Peyrade, Gilles Salles, Thierry Jo Molina, Thomas M. Habermann, Corinne Haioun, Richard Delarue, Nicolas Ketterer, Stephen M. Ansell, Ahmet Dogan, James R. Cerhan, Brian K. Link, Hervé Ghesquières, Susan L. Slager, Aurélie Verney, Anne J. Novak, Matthew J. Maurer, and Olivier Fitoussi
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Oncology ,Cancer Research ,medicine.medical_specialty ,FCGR2A ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Prospective cohort study ,business.industry ,FCGR3A ,Hematology ,General Medicine ,medicine.disease ,Lymphoma ,030220 oncology & carcinogenesis ,Immunology ,Rituximab ,business ,Diffuse large B-cell lymphoma ,Febrile neutropenia ,030215 immunology ,medicine.drug - 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.
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- 2016
21. Biological and Clinical Relevance of Associated Genomic Alterations in MYD88 L265P and non-L265P-Mutated Diffuse Large B-Cell Lymphoma: Analysis of 361 Cases
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Thierry Jo Molina, Fabrice Jardin, Marc André, Richard Delarue, Sylvain Mareschal, Philippe Bertrand, Thierry Fest, Corinne Haioun, Pierre-Julien Viailly, Martin Figeac, Philippe Ruminy, Dominique Penther, Vinciane Marchand, Sydney Dubois, Frederic Peyrade, Jean-Michel Picquenot, Karen Leroy, Jean-Philippe Jais, Christiane Copie-Bergman, Bruno Tesson, Catherine Maingonnat, Bettina Fabiani, Elodie Bohers, Fabienne Desmots, Hervé Tilly, Nicolas Ketterer, Thierry Lamy, Pauline Peyrouze, Gilles Salles, 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), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), 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), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Res Ctr, Institut Curie, Institut Curie [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Lille 2 - Faculté de Médecine, Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, CHU Pontchaillou [Rennes], 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 ), Etablissement français du sang [Rennes] (EFS Bretagne), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d’immunologie, de thérapie cellulaire et d’hématopoïèse, Hôpital Pontchaillou, 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), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie [Mondor], Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Cliniques Universitaires UCL Mont-Godinne, Department of Oncology, Lausanne Hospital, Lausanne Hospital, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, 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 de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Necker], Service d'informatique médicale et biostatistiques [CHU Necker], Institut Carnot Lymphome (CALYM), Faculté de Médecine Henri Warembourg - Université de Lille, Interactions cellulaires et moléculaires (ICM), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Microenvironnement et cancer (MiCa), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Anatomie et cytologie pathologiques [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), Département de Pathologie [CHU Necker], Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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 ), Normandie Université ( NU ), HEMATOLOGIE, CRLCC Henri Becquerel, 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 ), Dept Translat Res, Breast Canc Biol Grp, Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Institut pour la recherche sur le cancer de Lille [Lille] ( IRCL ) -Université de Lille, Droit et Santé, 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 ), Etablissement français du sang [Rennes] ( EFS Bretagne ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, 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 ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), 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 ), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Carnot CALYM [Pierre-Benite], Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Université Côte d'Azur (UCA)-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-IFR140-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Sorbonne Université (SU)-CHU Saint-Antoine [APHP], 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), MINES ParisTech - École nationale supérieure des mines de Paris, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), 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), MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), and 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)
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Male ,Oncology ,0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Bioinformatics ,medicine.disease_cause ,Biochemistry ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,Targeted therapy ,0302 clinical medicine ,CDKN2A ,hemic and lymphatic diseases ,Copy-number variation ,Aged, 80 and over ,Genetics ,0303 health sciences ,Mutation ,NF-kappa B ,High-Throughput Nucleotide Sequencing ,hemic and immune systems ,Genomics ,Hematology ,Middle Aged ,Prognosis ,3. Good health ,030220 oncology & carcinogenesis ,Female ,Lymphoma, Large B-Cell, Diffuse ,Signal Transduction ,Adult ,medicine.medical_specialty ,Adolescent ,DNA Copy Number Variations ,Immunology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Biology ,Genetic Heterogeneity ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Aged ,030304 developmental biology ,Genome, Human ,Genetic heterogeneity ,Germinal center ,Cancer ,Cell Biology ,CD79B ,medicine.disease ,Lymphoma ,Gene expression profiling ,030104 developmental biology ,Myeloid Differentiation Factor 88 ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
Introduction: MYD88 mutations, notably the recurrent gain-of-function L265P variant, are a distinguishing feature of Activated B-Cell like (ABC) Diffuse Large B Cell Lymphoma (DLBCL), leading to constitutive NFkB pathway activation. The frequency of MYD88 mutations in DLBCL and other hematologic malignancies is well described; however, there has not yet been a large-scale study of a MYD88 mutated patient cohort with additional Next Generation Sequencing (NGS), copy number variation (CNV), and gene expression data, in order to thoroughly characterize the associated genomic profiles of these patients. The aims of our study were to compare the L265P and non-L265P mutations in terms of pathological and genetic features, to better detail the genomic background associated with MYD88 mutations in order to delineate patients potentially sensitive to targeted therapies, and to define the prognostic value of MYD88 mutations according to different genomic contexts. Methods: A cohort of 361 DLBCL patients (94 MYD88 mutant and 267 MYD88 wild-type) was selected among the prospective, multicenter and randomized LNH-03B and LNH09-7B (NCT01195714) LYSA trials, as well as among patients sequenced at our institution as part of routine procedure. Cell of origin (COO) classification was obtained with HGU133+2.0 Affymetrix GeneChip arrays for 214 patients, with RT-MLPA for 77 patients1 and with Hans immunohistochemistry (IHC) method for 49 patients. All cases were submitted to next generation sequencing (NGS) focusing on 34 genes (Lymphopanel2) in order to analyze associated mutations and copy number variations (CNVs), as well as IHC, FISH, and clinical and prognostic analyses. Results: Importantly, we highlighted different genomic profiles for MYD88 L265P and MYD88 non-L265P mutant DLBCL, shedding light on their divergent backgrounds. Clustering analysis segregated subgroups according to associated genetic alterations among patients with either MYD88 L265P or non-L265P mutations. As such, clustering separated MYD88 L265P mutated DLBCL with associated PIM1 (52%), CD79B (52%), KMT2D (42%), and PRDM1 (32%) mutations, as well as MYD88 L265P mutated DLBCL with CDKN2A/B (67%/50%), PRDM1 (57%) and TNFAIP3 (52%) CNVs. We showed that associated CD79B and MYD88 L265P mutations act synergistically to increase NFkB pathway activation, although the majority of ABC MYD88 L265P mutant cases harbor downstream NFkB alterations, which can potentially predict BTK inhibitor resistance. Of note, although the MYD88 L265P variant was not an independent prognostic factor in ABC DLBCL, associated CD79B mutations significantly improved the survival of MYD88 L265P mutant ABC DLBCL in our cohort both in OS (p=0.02) and PFS (p=0.01), whereas the association of CARD11 or TNFAIP3 alterations did not impact survival. Interestingly, MYD88 mutant DLBCL cases were significantly more likely to experience central nervous system (CNS) relapse than MYD88 WT cases (p=0.02), as were MYD88 L265P mutant cases specifically (p=0.03). This result still tended toward statistical significance when considering only ABC patients (7 of 11 ABC CNS-relapsing cases were MYD88 mutant, p=0.1) but would have to be confirmed in a larger cohort. Conclusions: This study highlights the relative heterogeneity of MYD88 mutant DLBCBL, adding to the field's knowledge of the distinct genetic backgrounds of these subgroups. Our data highlights the theranostic and prognostic relevance of examining MYD88 and associated genomic alterations, emphasizing the usefulness of genomic profiling to best stratify patients for targeted therapy. 1. Mareschal S, Ruminy P, Bagacean C, et al. Accurate Classification of Germinal Center B-Cell-Like/Activated B-Cell-Like Diffuse Large B-Cell Lymphoma Using a Simple and Rapid Reverse Transcriptase-Multiplex Ligation-Dependent Probe Amplification Assay: A CALYM Study. The Journal of molecular diagnostics : JMD. 2015;17(3):273-283. 2. Dubois S, Viailly P-J, Mareschal S, et al. Next Generation Sequencing in Diffuse Large B Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study. Clinical cancer research : an official journal of the American Association for Cancer Research. 2016;22(12):2919-2928. Disclosures Salles: Novartis: Consultancy, Honoraria; Mundipharma: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding.
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- 2017
22. High-dose therapy and autologous hematopoietic stem cell transplant in T-cell lymphoma: a single center experience
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Anne Cairoli, Stefano Barelli, Nicolas Ketterer, and Michel A. Duchosal
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Lymphoma, T-Cell ,Single Center ,Transplantation, Autologous ,Young Adult ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,T-cell lymphoma ,Anaplastic large-cell lymphoma ,Aged ,Neoplasm Staging ,Univariate analysis ,Chemotherapy ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Lymphoma ,Surgery ,Treatment Outcome ,B symptoms ,Disease Progression ,Female ,Stem cell ,medicine.symptom ,business - Abstract
We report here the long-term outcome of autologous stem cell transplant in peripheral T-cell lymphoma (PTCL). Forty-three consecutive patients with PTCL diagnosed between 2000 and 2011 were treated with high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) in our center. Diagnoses included PTCL-not otherwise specified (n = 19), anaplastic large cell lymphoma (n = 11), angioimmunoblastic T-cell lymphoma (n = 5), enteropathy-associated T-cell lymphoma (n = 5) and other rare subtypes (n = 3). Thirty-six patients with a median age of 50 years (range 22-65) were transplanted in first response and seven after relapse. After a median follow-up of 63 months, estimated overall survival at 12 years was 40%, progression-free survival at 12 years was 34% and event-free survival at 12 years was 30%. On univariate analysis, age less than 50 years and no B symptoms at diagnosis were significantly associated with prolonged overall and progression-free-survival. HDCT/ASCT for peripheral T-cell lymphoma can lead to long-term survival for patients responding to induction chemotherapy.
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- 2014
23. Y
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Michèle, Voegeli, Stephanie, Rondeau, Simona, Berardi Vilei, Erika, Lerch, Luciano, Wannesson, Thomas, Pabst, Jochen, Rentschler, Mario, Bargetzi, Lorenz, Jost, Nicolas, Ketterer, Angelika, Bischof Delaloye, and Michele, Ghielmini
- Subjects
Aged, 80 and over ,Male ,Time Factors ,Transplantation Conditioning ,Lymphoma ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Transplantation, Autologous ,Treatment Outcome ,Drug Resistance, Neoplasm ,Recurrence ,Antineoplastic Combined Chemotherapy Protocols ,Retreatment ,Humans ,Female ,Yttrium Radioisotopes ,Neoplasm Grading ,Melphalan ,Aged - 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
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- 2016
24. Primary bone diffuse large B-cell lymphoma: a retrospective evaluation on 76 cases from French institutional and LYSA studies
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Christophe Bonnet, Frédérique Larousserie, Hervé Tilly, Christian Roux, Gilles Salles, Bénédicte Deau, Estelle Blanc-Autran, Corinne Haioun, David Biau, Richard Delarue, Stephanie Harel, Christian Gisselbrecht, Marielle Legoff, Nicolas Ketterer, Jerome Tamburini, Vincent Ribrag, Pauline Brice, Frederic Peyrade, Didier Bouscary, Patricia Franchi, Philippe Anract, Christian Recher, Lise Willems, Sylvain Pilorge, Institut des Matériaux Jean Rouxel ( IMN ), Université de Nantes ( UN ) -Centre National de la Recherche Scientifique ( CNRS ), Hématologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), CHU Cochin [AP-HP], Service d’Hématologie Clinique, CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Chercheur indépendant, Géomagnétisme et paléomagnétisme et géophysique de surface, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut de Physique du Globe de Paris-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Dynamique des Fluides ( DynFluid ), Arts et Métiers ParisTech-Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Service d'orthopédie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], GELA, Groupe d'Etude des Lymphomes de l'Adulte, Department of Oncology, Lausanne Hospital, Lausanne Hospital, Service d'hématologie, Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
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Male ,Cancer Research ,Pathology ,[ SDV.CAN ] Life Sciences [q-bio]/Cancer ,rituximab ,0302 clinical medicine ,International Prognostic Index ,immune system diseases ,hemic and lymphatic diseases ,Positron Emission Tomography Computed Tomography ,Antineoplastic Combined Chemotherapy Protocols ,aa-IPI ,Randomized Controlled Trials as Topic ,Aged, 80 and over ,Univariate analysis ,medicine.diagnostic_test ,primary bone lymphoma ,Hematology ,Middle Aged ,Combined Modality Therapy ,Treatment Outcome ,Oncology ,Positron emission tomography ,030220 oncology & carcinogenesis ,Rituximab ,Female ,Radiology ,France ,Lymphoma, Large B-Cell, Diffuse ,medicine.drug ,Adult ,medicine.medical_specialty ,Bone Neoplasms ,03 medical and health sciences ,medicine ,Humans ,radiotherapy ,Aged ,Neoplasm Staging ,Retrospective Studies ,Fluorodeoxyglucose ,Proportional hazards model ,business.industry ,medicine.disease ,Survival Analysis ,Lymphoma ,DLBCL ,business ,Diffuse large B-cell lymphoma ,030215 immunology - Abstract
International audience; Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare DLBCL location variant. We treated 76 PB-DLBCL patients by immuno-chemotherapy, resulting in an 84% sustained complete remission rate and a 78.9% survival over a 4.7-year median follow-up period. Ann Arbor stage IV and high age-adjusted international prognostic index were predictive of adverse outcome in univariate analysis. In multivariate analysis using a Cox model, only aa-IPI predicted long-term survival. While based on a limited number of cases, we suggested that radiotherapy may be useful as a consolidation modality in PB-DLBCL. We also suggested that positron emission tomography/CT scan should be interpreted with caution due to a persistent [18F]fluorodeoxyglucose [18FDG] uptake of bone lesions even after remission in some in PB-DLBCL patients. Our study based on a homogeneous cohort of PB-DLBCL patients confirmed the favorable outcome of this DLBCL variant and support the implementation of prospective clinical trials in this disease.
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- 2016
25. Superiority of the Triple Combination of Bortezomib-Thalidomide-Dexamethasone Over the Dual Combination of Thalidomide-Dexamethasone in Patients With Multiple Myeloma Progressing or Relapsing After Autologous Transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial From the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation
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Brigitte Kolb, Simona Iacobelli, Roman Hájek, Carine Chaleteix, Norbert Claude Gorin, Jean Luc Harousseau, Francesco Onida, Mohamad Mohty, Gösta Gahrton, Dietger Niederwieser, Philippe Moreau, Philippe Casassus, Heinz Ludwig, Ingrid Lafon, Bernd Hertenstein, Brigitte Pegourie, Andrew Cakana, Mauricette Michallet, Nicolas Ketterer, Alois Gratwohl, Marleen van Os, Mamoun Dib, Jean Fontan, Giuseppe Milone, Chantal Doyen, Curly Morris, Tamas Masszi, Laurent Garderet, Christian Koenecke, and Theo de Witte
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Transplantation, Autologous ,Gastroenterology ,Dexamethasone ,Disease-Free Survival ,Drug Administration Schedule ,Settore MED/01 - Statistica Medica ,Bortezomib ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Autologous transplantation ,Survival rate ,Multiple myeloma ,Aged ,business.industry ,Hazard ratio ,Translational research Immune Regulation [ONCOL 3] ,Middle Aged ,medicine.disease ,Boronic Acids ,Thalidomide ,3. Good health ,Surgery ,Transplantation ,Treatment Outcome ,Oncology ,Pyrazines ,030220 oncology & carcinogenesis ,Female ,Multiple Myeloma ,business ,Stem Cell Transplantation ,030215 immunology ,medicine.drug - Abstract
Purpose This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT). Patients and Methods Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m2 intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day 21) for eight cycles (6 months), and then on days 1, 8, 15, and 22 with a 20-day rest period (day 23 to day 42) for four cycles (6 months). Results Median time to progression (primary end point) was significantly longer with VTD than TD (19.5 v 13.8 months; hazard ratio, 0.59; 95% CI, 0.44 to 0.80; P = .001), the complete response plus near-complete response rate was higher (45% v 21%; P = .001), and the median duration of response was longer (17.9 v 13.4 months; P = .04). The 24-month survival rate was in favor of VTD (71% v 65%; P = .093). Grade 3 peripheral neuropathy was more frequent with VTD (29% v 12%; P = .001) as were the rates of grades 3 and 4 infection and thrombocytopenia. Conclusion VTD was more effective than TD in the treatment of patients with MM with progressive or relapsing disease post-ASCT but was associated with a higher incidence of grade 3 neurotoxicity.
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- 2012
26. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study
- Author
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Danielle Canioni, Fabrice Jardin, Peggy Cuillière-Dartigues, Philippe Gaulard, Frederic Peyrade, Marie Parrens, Jean-Philippe Jais, Richard Delarue, Gilles Salles, Nicolas Ketterer, Reiner Siebert, Christian Recher, Karen Leroy, Hervé Tilly, Bettina Fabiani, Maryse Baia, Christiane Copie-Bergman, Tony Petrella, Corinne Haioun, Karim Belhadj, Inga Nagel, Josette Brière, Thierry Jo Molina, 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), INSERM U955, équipe 9, 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)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Service d'anatomo-pathologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Hématologie Biologique, Service de Pathologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d’Hématologie [CHU Purpan, Toulouse], Centre Hospitalier Universitaire de Purpan (CHU Purpan), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Department of Oncology, Lausanne Hospital, Lausanne Hospital, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service d'hématologie clinique, Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Groupe d'étude des proliférations lymphoïdes (GPL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), 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), CIC - Biotherapie - CHU Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'informatique médicale et biostatistiques [CHU Necker], Hôpital Hôtel Dieu, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hématologie [CHU Toulouse], CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre Antoine Lacassagne, CRLCC Antoine Lacassagne, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
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Adult ,Male ,Immunoglobulin gene ,Adolescent ,[SDV]Life Sciences [q-bio] ,Immunology ,Immunoglobulins ,Chromosomal translocation ,Biology ,Biochemistry ,Disease-Free Survival ,Translocation, Genetic ,Proto-Oncogene Proteins c-myc ,Antibodies, Monoclonal, Murine-Derived ,03 medical and health sciences ,0302 clinical medicine ,International Prognostic Index ,immune system diseases ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cyclophosphamide ,Survival rate ,ComputingMilieux_MISCELLANEOUS ,Aged ,030304 developmental biology ,Aged, 80 and over ,Gene Rearrangement ,0303 health sciences ,Cell Biology ,Hematology ,Gene rearrangement ,Middle Aged ,medicine.disease ,BCL6 ,3. Good health ,Lymphoma ,Survival Rate ,Doxorubicin ,Vincristine ,030220 oncology & carcinogenesis ,Cancer research ,Prednisone ,Female ,Lymphoma, Large B-Cell, Diffuse ,Rituximab ,Diffuse large B-cell lymphoma - Abstract
Diffuse Large B-Cell lymphoma (DLBCL) with MYC rearrangement ( MYC -R) carries an unfavorable outcome. We explored the prognostic value of MYC translocation partner gene in a series of MYC -R de novo DLBCL patients enrolled in first-line prospective clinical trials of the GELA/LYSA and treated with rituximab-anthracyclin-based chemotherapy. Seven hundred seventy four DLBCL cases characterized for cell of origin by the Hans classifier were analysed using fluorescence in situ hybridization (FISH) with BCL2 , BCL6 , MYC , IGK , IGL breakapart and IGH/MYC , IGK/MYC , IGL/MYC fusion probes. MYC rearrangement ( MYC -R) was observed in 51/574 (8.9%) evaluable DLBCL. MYC -R cases were predominantly of germinal centre B-cell-like subtype 37/51(74%) with no distinctive morphological and phenotypic features. Nineteen were MYC single-hit ( MYC -SH) and 32 MYC double-hit ( MYC -DH) ( MYC plus BCL2 and/or BCL6 ) DLBCL. MYC translocation partner was an immunoglobulin gene in 24 cases ( MYC-IG ) and a non-immunoglobulin gene ( MYC-non-IG ) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) ( P=.0002 ) compared to MYC -negative patients, whereas no survival difference was observed between MYC-non-IG and MYC -negative patients. In multivariate analyses MYC-IG predicted poor PFS ( P=.0051 ) and OS ( P=.0006 ) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC rearrangement is correlated to MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC rearrangement who should be routinely characterized according to MYC partner gene. Trials are individually registered with www.ClinicalTrials.gov numbers NCT00144807, NCT01087424, NCT00169143, NCT00144755, NCT00140660, NCT00140595 and NCT00135499.
- Published
- 2015
27. Six of 12 Relapsed or Refractory Indolent Lymphoma Patients Treated 10 Years Ago with 131I-Tositumomab Remain in Complete Remission
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Oliver W. Press, John O. Prior, Claudine Helg, Cristian Antonescu, Marek Kosinski, Nicolas Ketterer, Angelika Bischof Delaloye, and Franz Buchegger
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Adult ,Male ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,131I-tositumomab ,Antineoplastic Agents ,Tositumomab ,Refractory ,Bone Marrow ,hemic and lymphatic diseases ,Internal medicine ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Radiometry ,Bone Marrow Diseases ,Aged ,Chemotherapy ,business.industry ,Lymphoma, Non-Hodgkin ,Remission Induction ,Antibodies, Monoclonal ,Middle Aged ,Radioimmunotherapy ,Antigens, CD20 ,Prognosis ,medicine.disease ,Recombinant Proteins ,United States ,Lymphoma ,Indolent lymphoma ,Europe ,England ,Drug Resistance, Neoplasm ,Interferon Type I ,Female ,Rituximab ,Neoplasm Recurrence, Local ,Radiopharmaceuticals ,business ,Switzerland ,Follow-Up Studies ,medicine.drug - Abstract
UNLABELLED The purpose of our study was to update the safety and efficacy results of radioimmunotherapy in relapsed or resistant indolent or transformed non-Hodgkin lymphoma. METHODS More than 9 y ago, we treated 12 indolent and 4 transformed, relapsed or refractory lymphoma patients with a single administration of nonmyeloablative therapy with tositumomab and (131)I-tositumomab. The 16 patients had a mean of 3.1 (range, 1-6) previous chemotherapy and antibody treatments. RESULTS Six of 12 relapsed indolent lymphoma patients remain disease-free a mean of 9.8 y (range, 8.6-10.7 y) after radioimmunotherapy. Three of 4 transformed lymphoma patients progressed after radioimmunotherapy, and 1 patient had a partial response of 10 mo. CONCLUSION Optimal patient benefit might be obtained in indolent lymphoma when administering radioimmunotherapy up-front in combination with chemotherapy and rituximab treatment. However, these results show that radioimmunotherapy alone achieved long-lasting remissions in 6 of 12 (50%) indolent lymphoma patients in relapse after 1 or multiple chemotherapies.
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- 2011
28. Achievement of VGPR to induction therapy is an important prognostic factor for longer PFS in the IFM 2005-01 trial
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Hervé Avet-Loiseau, Jean-Luc Harousseau, Brigitte Kolb, Thierry Facon, Catherine Sebban, Mamoun Dib, Jean Fontan, Claire Mathiot, Michel Attal, Chantal Doyen, Dixie Lee Esseltine, Laurent Voillat, Jean-Gabriel Fuzibet, Brigitte Pegourie, Philippe Moreau, Bernard Grosbois, Anne-Marie Stoppa, Carine Chaleteix, Cyrille Hulin, Laurent Garderet, Lucie Planche, Jérôme Jaubert, and Nicolas Ketterer
- Subjects
Adult ,Oncology ,medicine.medical_specialty ,Time Factors ,Multivariate analysis ,Immunology ,Biochemistry ,Disease-Free Survival ,law.invention ,Autologous stem-cell transplantation ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Very Good Partial Response ,Intention-to-treat analysis ,Hematology ,Bortezomib ,business.industry ,Remission Induction ,Cell Biology ,Middle Aged ,Prognosis ,Intention to Treat Analysis ,Surgery ,Clinical trial ,Treatment Outcome ,Multiple Myeloma ,business ,medicine.drug - Abstract
In the 2005-01 trial, we have demonstrated that bortezomib-dexamethasone as induction therapy before autologous stem cell transplantation was superior to vincristine-adriamycin-dexamethasone. We conducted a post-hoc analysis to assess the prognostic impact of initial characteristics as well as response to therapy in patients enrolled in this study. Multivariate analysis showed that ISS stages 2 and 3 and achievement of response less than very good partial response (VGPR) both after induction therapy and after autologous stem cell transplantation were adverse prognostic factors for progression-free survival, the most important one being achievement of response less than VGPR after induction. Progression-free survival was significantly improved with bortezomib-dexamethasone induction therapy in patients with poor-risk cytogenetics and ISS stages 2 and 3 compared with vincristine-adriamycin-dexamethasone. In these 2 groups of patients, achievement of at least VGPR after induction was of major importance. This study is registered with EudraCT (https://eudract.ema.europa.eu; EUDRACT 2005-000537-38) and http://clinicaltrials.gov (NCT00200681).
- Published
- 2011
29. Clinical characteristics and outcome of isolated extracerebral relapses of primary central nervous system lymphoma: a case series
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Arnaud de la Fouchardière, Celine Ferlay, Sawyna Provencher, Alain Devidas, Khaoula Alaoui-Slimani, André Delannoy, Antoine Thyss, Catherine Chassagne-Clement, Herve Ghesquieres, P. Biron, Bernard De Prijck, Jean-Yves Blay, Nicolas Ketterer, Hervé Tilly, Catherine Sebban, and Stéphane Leprêtre
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Adult ,Male ,Cancer Research ,Systemic disease ,medicine.medical_specialty ,medicine.medical_treatment ,Central nervous system ,Gastroenterology ,Central Nervous System Neoplasms ,Autologous stem-cell transplantation ,Recurrence ,Internal medicine ,medicine ,Humans ,Aged ,Aged, 80 and over ,Chemotherapy ,business.industry ,Lymphoma, Non-Hodgkin ,Primary central nervous system lymphoma ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Surgery ,Radiation therapy ,Methotrexate ,Treatment Outcome ,medicine.anatomical_structure ,Oncology ,Cohort ,Female ,business ,medicine.drug - Abstract
There is very limited data on isolated systemic relapses of primary central nervous system lymphomas (PCNSL). We retrospectively reviewed the clinical characteristics and outcome of 10 patients with isolated systemic disease among 209 patients with PCNSL mainly treated with methotrexate-based chemotherapy (CT) with or without radiation therapy (RT). Isolated systemic relapse remained rare (4.8%, 10/209 patients). Median time from initial diagnosis to relapse was 33 months (range, 3–94). Sites of relapse were mostly extranodal. Three patients presented with early extra-cerebral (EC) relapse 3, 5 and 8 months from the beginning of initial treatment, respectively, and 7 patients had later relapses (range, 17–94 months). Treatment at relapse included surgery alone, RT alone, CT with or without radiotherapy, or CT with autologous stem cell transplantation (ASCT). Median overall survival (OS) after relapse was 15.5 months (range, 5.8–24.5) compared to 4.6 months (range, 3.6–6.5) for patients with central nervous system (CNS) relapse (p = 0.35). In conclusion, isolated systemic relapses exist but are infrequent. Early EC relapse suggests the presence of systemic disease undetectable by conventional evaluation at initial diagnosis. Patient follow-up must be prolonged because systemic relapse can occur as late as 10 years after initial diagnosis. Whether EC relapses of PCNSL have a better prognosis than CNS relapses needs to be assessed in a larger cohort. Copyright © 2010 John Wiley & Sons, Ltd.
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- 2011
30. Pegfilgrastim to accelerate neutrophil engraftment following peripheral blood stem cell transplant and reduce the duration of neutropenia, hospitalization, and use of intravenous antibiotics: a phase II study in multiple myeloma and lymphoma and comparison with filgrastim-treated matched controls
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Nicolas Ketterer, Anne Rosselet-christ, Michele Ghielmini, Emanuele Zucca, François Luthi, Luciano Wannesson, Mauro Baglioni, and Lucia Marelli
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Neutropenia ,Time Factors ,Filgrastim ,Lymphoma ,Platelet Engraftment ,Neutrophils ,Matched-Pair Analysis ,medicine.medical_treatment ,Gastroenterology ,Drug Administration Schedule ,Polyethylene Glycols ,Young Adult ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,Humans ,Medicine ,Multiple myeloma ,Aged ,Peripheral Blood Stem Cell Transplantation ,Chemotherapy ,Neutrophil Engraftment ,business.industry ,Hematology ,Antibiotic Prophylaxis ,Length of Stay ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Anti-Bacterial Agents ,Granulocyte colony-stimulating factor ,Surgery ,Hospitalization ,Oncology ,Injections, Intravenous ,Female ,Multiple Myeloma ,business ,Pegfilgrastim ,medicine.drug - Abstract
This trial was aimed to explore the efficacy of pegfilgrastim to accelerate neutrophil engraftment after stem cell autotransplant. Twenty patients with multiple myeloma and 20 with lymphoma received pegfilgrastim 6 mg on day +1. Forty cases treated with daily filgrastim starting at median day +7 (5-7), matched by age, sex, diagnosis, high-dose chemotherapy schedule, CD34 + cell-dose, and prior therapy lines, were used for comparison. Median time to neutrophil engraftment was 9.5 vs. 11 days for pegfilgrastim and filgrastim, respectively (p0.0001). Likewise, duration of neutropenia, intravenous antibiotic use, and hospitalization favored pegfilgrastim, while platelet engraftment, transfusion requirement, and fever duration were equivalent in both groups. No grade ≥ 3 toxicities were observed. Patients with lymphoma performed similarly to the entire cohort, while patients with myeloma showed faster neutrophil engraftment and shorter neutropenia but not shorter hospitalization and antibiotic use. The possibility of different outcomes for lymphoma and myeloma suggests that stratification by diagnosis may be useful in future phase III studies.
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- 2011
31. Follicular lymphoma at relapse after rituximab containing regimens: comparison of time to event intervals prior to and after 90Y-ibritumomab-tiuxetan
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Eleonora Russo, Francesco Cicone, Andrea Carpaneto, John O. Prior, Nicolas Ketterer, Francesco Scopinaro, and Angelika Bischof Delaloye
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Adult ,Male ,Oncology ,zevalin ,radioimmunotherapy ,non-Hodgkin Lymphoma ,radionuclide therapy ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Follicular lymphoma ,Ibritumomab tiuxetan ,Disease-Free Survival ,Antibodies, Monoclonal, Murine-Derived ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Yttrium Radioisotopes ,Lymphoma, Follicular ,Aged ,Neoplasm Staging ,Retrospective Studies ,Univariate analysis ,business.industry ,Antibodies, Monoclonal ,Retrospective cohort study ,Hematology ,General Medicine ,Middle Aged ,Radioimmunotherapy ,medicine.disease ,Surgery ,Lymphoma ,Female ,Rituximab ,Refractory Follicular Lymphoma ,business ,medicine.drug - Abstract
Radioimmunotherapies with Zevalin® (RIT-Z) showed encouraging results in patients with relapsed/refractory follicular lymphoma (FL), leading frequently to failure-free intervals longer than those achieved by the last previous therapy. We compared time-to-event variables obtained before and after RIT-Z in patients with relapsed FL, previously exposed to rituximab. All patients with relapsed non-transformed, non-refractory, non-rituximab-naïve FL who have been treated with RIT-Z in two different centres in Europe were included. Staging and response were assessed by contrast-enhanced CT in all patients; PET/CT was performed according to local availability. Event-free survival (EFS) and time to next treatment (TTNT) following the last previous therapy and after RIT-Z were compared. Pre-therapy characteristics were tested in univariate analyses for prediction of outcomes. A description of the patterns of relapse was also provided. Among 70 patients treated, only 16 fulfilled the inclusion criteria. They were treated with a median of 3 prior lines of chemo-immunotherapies, including a median of 2 rituximab-containing regimens; 6 patients had undergone myeloablative chemotherapy with autologous stem cell rescue (ASCT). Overall response rates were 10 (62%) CR/CRu, 3 (19%) PR and 3 (19%) PD; response rates were similar in patients with prior ASCT. After RIT-Z only few patients obtained EFS and TTNT longer than after the last previous therapy. All four patients receiving rituximab maintenance were without progression 12 months after RIT-Z. Relapses occurred in both previously and newly involved sites; a significant association was found between the number of pathologic sites involved prior to RIT-Z and subsequent TTNT. Despite the excellent response rate, the duration of response was shorter than the previous one confirming the known trend of relapses to occur earlier after subsequent treatments. Rituximab maintenance after RIT-Z showed encouraging results in terms of prolonging EFS, warranting further studies.
- Published
- 2010
32. Stem cell transplantation after alemtuzumab in T-cell prolymphocytic leukaemia results in longer survival than after alemtuzumab alone: a multicentre retrospective study
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Claire Dearden, Monica Else, Geir E. Tjønnfjord, Estella Matutes, John M. Carter, Daniel Catovsky, Bruno Cazin, Mark Ethell, Biju Krishnan, Nicolas Ketterer, and Dennis A. Carney
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Antibodies, Neoplasm ,medicine.medical_treatment ,Antineoplastic Agents ,Hematopoietic stem cell transplantation ,Antibodies, Monoclonal, Humanized ,Internal medicine ,medicine ,Humans ,Prolymphocytic leukemia ,Alemtuzumab ,Survival analysis ,Aged ,Retrospective Studies ,business.industry ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Hematology ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Survival Analysis ,Transplantation ,Leukemia ,Treatment Outcome ,Leukemia, Prolymphocytic, T-Cell ,Immunology ,T-cell prolymphocytic leukemia ,Female ,Stem cell ,business ,medicine.drug - Published
- 2010
33. Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis: a single-centre experience
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Anne Rosselet, Michel A. Duchosal, Nicolas Ketterer, Pascal Meier, Tibor Kovacsovics, Anne Cairoli, and Valérie Frossard
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Adult ,Male ,Melphalan ,medicine.medical_specialty ,medicine.medical_treatment ,Transplantation, Autologous ,Autologous stem-cell transplantation ,Aged ,Amyloidosis/complications ,Amyloidosis/mortality ,Female ,Hematopoietic Stem Cell Transplantation/adverse effects ,Hematopoietic Stem Cell Transplantation/methods ,Humans ,Kidney Diseases/therapy ,Melphalan/administration & dosage ,Middle Aged ,Myeloablative Agonists/administration & dosage ,Remission Induction ,Survival Rate ,Treatment Outcome ,medicine ,AL amyloidosis ,Survival rate ,Dialysis ,Chemotherapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Amyloidosis ,Hematology ,General Medicine ,Myeloablative Agonists ,medicine.disease ,Surgery ,Transplantation ,Kidney Diseases ,business ,Primary systemic amyloidosis ,medicine.drug - 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 100 days. 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 12 months. Half of all the patients (n = 8) were alive after a median follow-up of 33 months, 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
- 2008
34. Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study
- Author
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Devinder Gill, E. Van Den Neste, B. Glass, Dc Linch, Christian Gisselbrecht, Noel-Jean Milpied, Catherine Thieblemont, John Radford, Craig H. Moskowitz, Marek Trneny, David D.F. Ma, Ofer Shpilberg, Gilles Salles, Jean Briere, Nicolas Ketterer, Nicolas Mounier, Norbert Schmitz, and Ulrich Dührsen
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Medizin ,Salvage therapy ,Aggressive lymphoma ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Autologous stem-cell transplantation ,International Prognostic Index ,Recurrence ,Internal medicine ,medicine ,Refractory Diffuse Large B-Cell Lymphoma ,Humans ,Autografts ,Survival rate ,Aged ,Salvage Therapy ,Transplantation ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Survival Rate ,030220 oncology & carcinogenesis ,Female ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,030215 immunology ,Stem Cell Transplantation - 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
- Published
- 2015
35. Current status and updated recommendations for diagnosis and treatment of plasma cell myeloma in Switzerland
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Urs Hess, Nicolas Ketterer, Panagiotis Samaras, Dominik Heim, Daniel Betticher, Christoph Renner, Erika Lerch, Thomas Matthes, Mario Bargetzi, Michel A. Duchosal, Ulrich Mey, Thilo Zander, Thomas Pabst, Christian Taverna, University of Zurich, and Renner, Christoph
- Subjects
medicine.medical_specialty ,610 Medicine & health ,2700 General Medicine ,Monoclonal Gammopathy of Undetermined Significance ,Maintenance Chemotherapy ,Quality of life ,Recurrence ,hemic and lymphatic diseases ,Plasma Cell Myeloma ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Intensive care medicine ,Multiple myeloma ,Lenalidomide ,Neoplasm Staging ,ddc:616 ,business.industry ,Bortezomib ,Antineoplastic Combined Chemotherapy Protocols/therapeutic use ,Monoclonal Gammopathy of Undetermined Significance/pathology ,Multiple Myeloma/diagnosis ,Multiple Myeloma/therapy ,Hematopoietic Stem Cell Transplantation ,General Medicine ,medicine.disease ,Thalidomide ,Consolidation Chemotherapy ,10032 Clinic for Oncology and Hematology ,Relapsed refractory ,Practice Guidelines as Topic ,Retreatment ,business ,Multiple Myeloma ,Median survival ,Switzerland ,medicine.drug - 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
36. Tandem autologous stem cell transplantation in high-risk de novo multiple myeloma: final results of the prospective and randomized IFM 99-04 protocol
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Lotfi Benboubker, Jean-Luc Harousseau, Frédéric Garban, Philippe Moreau, Cyrille Hullin, Gerald Marit, Mathieu Monconduit, Jean-Gabriel Fuzibet, Ibrahim Yakoub-Agha, Régis Bataille, Mauricette Michallet, Laurent Voillat, Philippe Casassus, Jean-Jacques Sotto, Nicolas Ketterer, Michel Attal, Christian Berthou, Chantal Doyen, and Albert Najman
- Subjects
Adult ,Male ,Melphalan ,medicine.medical_specialty ,Transplantation Conditioning ,Randomization ,medicine.medical_treatment ,Immunology ,Population ,Urology ,Transplantation, Autologous ,Biochemistry ,Dexamethasone ,law.invention ,Autologous stem-cell transplantation ,Randomized controlled trial ,Risk Factors ,law ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,education ,Multiple myeloma ,Aged ,Chemotherapy ,education.field_of_study ,Chromosomes, Human, Pair 13 ,Interleukin-6 ,business.industry ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Survival Analysis ,Surgery ,Female ,Chromosome Deletion ,Multiple Myeloma ,beta 2-Microglobulin ,business ,medicine.drug - Abstract
The combination of high levels of beta2-microglobulin (beta2-m) and chromosome 13 deletion allows identification of a high-risk subgroup of patients with de novo multiple myeloma (MM). In this population of patients, we have evaluated the impact of a murine anti-interleukin 6 (anti-IL-6) monoclonal antibody (BE-8) as part of the second conditioning regimen in a multicenter prospective randomized trial of tandem autologous stem cell transplantation (ASCT). Conditioning for the first ASCT was accomplished with melphalan 200 mg/m2 and for the second one with melphalan 220 mg/m2 plus dexamethasone with or without BE-8 infusion. This trial included 219 patients, of whom 166 were randomized, 85 without BE-8 (arm A) and 81 with BE-8 (arm B). The median overall survival (OS) and event-free survival (EFS) times of the whole group of patients were 41 and 30 months, respectively. Response rates, OS, and EFS were not different between the 2 arms of the trial. OS at 54 months was 46% in arm A and 51% in arm B (P = .90); median EFS was 35 months in arm A and 31 in arm B (P = .39). In high-risk patients the dose intensity of melphalan at 420 mg/m2 led to encouraging results, but the addition of anti-IL-6 monoclonal antibody to the second conditioning regimen did not improve either OS nor EFS.
- Published
- 2005
37. Repeated injections of 131I-rituximab show patient-specific stable biodistribution and tissue kinetics
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P. Monnin, Carine Grannavel, Marek Kosinski, Francis R. Verdun, Angelika Bischof Delaloye, Nicolas Ketterer, Franz Buchegger, Andreas O. Schaffland, Cristian Antonescu, and Tibor Kovacsovics
- Subjects
Male ,Biodistribution ,Metabolic Clearance Rate ,medicine.medical_treatment ,Spleen ,Injections, Intralesional ,Whole-Body Counting ,Drug Administration Schedule ,Antibodies, Monoclonal, Murine-Derived ,Pharmacokinetics ,medicine ,Humans ,Dosimetry ,Tissue Distribution ,Radiology, Nuclear Medicine and imaging ,Radiometry ,Infusions, Intralesional ,Antibodies, Monoclonal ,Body Burden ,Female ,Kinetics ,Lymphoma, Non-Hodgkin ,Middle Aged ,Organ Specificity ,Radiopharmaceuticals ,Radiotherapy Dosage ,Relative Biological Effectiveness ,business.industry ,General Medicine ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,Radioimmunotherapy ,Rituximab ,Nuclear medicine ,business ,medicine.drug ,Blood sampling - Abstract
PURPOSE: It is generally assumed that the biodistribution and pharmacokinetics of radiolabelled antibodies remain similar between dosimetric and therapeutic injections in radioimmunotherapy. However, circulation half-lives of unlabelled rituximab have been reported to increase progressively after the weekly injections of standard therapy doses. The aim of this study was to evaluate the evolution of the pharmacokinetics of repeated 131I-rituximab injections during treatment with unlabelled rituximab in patients with non-Hodgkin's lymphoma (NHL). METHODS: Patients received standard weekly therapy with rituximab (375 mg/m2) for 4 weeks and a fifth injection at 7 or 8 weeks. Each patient had three additional injections of 185 MBq 131I-rituximab in either treatment weeks 1, 3 and 7 (two patients) or weeks 2, 4 and 8 (two patients). The 12 radiolabelled antibody injections were followed by three whole-body (WB) scintigraphic studies during 1 week and blood sampling on the same occasions. Additional WB scans were performed after 2 and 4 weeks post 131I-rituximab injection prior to the second and third injections, respectively. RESULTS: A single exponential radioactivity decrease for WB, liver, spleen, kidneys and heart was observed. Biodistribution and half-lives were patient specific, and without significant change after the second or third injection compared with the first one. Blood T(1/2)beta, calculated from the sequential blood samples and fitted to a bi-exponential curve, was similar to the T(1/2) of heart and liver but shorter than that of WB and kidneys. Effective radiation dose calculated from attenuation-corrected WB scans and blood using Mirdose3.1 was 0.53+0.05 mSv/MBq (range 0.48-0.59 mSv/MBq). Radiation dose was highest for spleen and kidneys, followed by heart and liver. CONCLUSION: These results show that the biodistribution and tissue kinetics of 131I-rituximab, while specific to each patient, remained constant during unlabelled antibody therapy. RIT radiation doses can therefore be reliably extrapolated from a preceding dosimetry study.
- Published
- 2005
38. Effect of Single-Agent Rituximab Given at the Standard Schedule or As Prolonged Treatment in Patients With Mantle Cell Lymphoma: A Study of the Swiss Group for Clinical Cancer Research (SAKK)
- Author
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Sergio Cogliatti, Rolf A. Stahel, Michele Ghielmini, Hubert Schefer, Ursula Waltzer, Shu-Fang Hsu Schmitz, Nicolas Ketterer, Thomas Cerny, Mario Bargetzi, Francesco Bertoni, Martin F. Fey, Gabriella Pichert, and Daniel Betticher
- Subjects
Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Anemia ,Antineoplastic Agents ,Lymphoma, Mantle-Cell ,Gastroenterology ,Drug Administration Schedule ,law.invention ,Antibodies, Monoclonal, Murine-Derived ,Randomized controlled trial ,Refractory ,law ,Internal medicine ,medicine ,Humans ,Aged ,Aged, 80 and over ,business.industry ,Antibodies, Monoclonal ,Middle Aged ,medicine.disease ,Surgery ,Lymphoma ,Clinical trial ,medicine.anatomical_structure ,Oncology ,Female ,Mantle cell lymphoma ,Rituximab ,Bone marrow ,business ,medicine.drug - Abstract
Purpose To evaluate the effect of single-agent rituximab given at the standard or a prolonged schedule in patients with newly diagnosed, or refractory or relapsed mantle cell lymphoma (MCL). Patients and Methods After induction treatment with the standard schedule (375 mg/m2 weekly × 4), patients who were responding or who had stable disease at week 12 from the start of treatment were randomly assigned to no further treatment (arm A) or prolonged rituximab administration (375 mg/m2) every 8 weeks for four times (arm B). Results The trial enrolled 104 patients. After induction, clinical response was 27% with 2% complete responses. Among patients with detectable t(11;14)-positive cells in blood and bone marrow at baseline, four of 20, and one of 14, respectively, became polymerase chain-reaction–negative after induction. Anemia was the only adverse predictor of response in the multivariate analysis. After a median follow-up of 29 months, response rate and duration of response were not significantly different between the two schedules in 61 randomly assigned patients. Median event-free survival (EFS) was 6 months in arm A versus 12 months in arm B; the difference was not significant (P = .1). Prolonged treatment seemed to improve EFS in the subgroup of pretreated patients (5 months in arm A v 11 months in arm B; P = .04). Thirteen percent of patients in arm A and 9% in arm B presented with grade 3 to 4 hematologic toxicity. Conclusion Single-agent rituximab is active in MCL, but the addition of four single doses at 8-week intervals does not seem to significantly improve response rate, duration of response, or EFS after treatment with the standard schedule.
- Published
- 2005
39. Acute coronary syndrome upon receiving carmustine infusion before autologous stem-cell transplantation
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Nicolas Ketterer, Anne Rosselet, François Luthi, Stéphanie Berthouzoz, and Christine Waibel Pachinger
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Cancer Research ,medicine.medical_specialty ,Acute coronary syndrome ,Carmustine ,business.industry ,medicine.medical_treatment ,Hematology ,General Medicine ,Hematopoietic stem cell transplantation ,medicine.disease ,Surgery ,Autologous stem-cell transplantation ,Oncology ,Medicine ,Transplantation Conditioning ,business ,medicine.drug - Published
- 2012
40. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy
- Author
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Thierry Jo Molina, Susan L. Slager, Carrie A. Thompson, Thomas E. Witzig, Ivana N. Micallef, Olivier Fitoussi, Jean-Philippe Jais, Emmanuelle Nicolas-Virelizier, Nicolas Ketterer, Thomas M. Habermann, Gilles Salles, Hervé Ghesquières, Cristine Allmer, Corinne Haioun, Hervé Tilly, Richard Delarue, Sergei Syrbu, William R. Macon, Brian K. Link, Matthew J. Maurer, Paul J. Kurtin, James R. Cerhan, and Frederic Peyrade
- Subjects
Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Adolescent ,Disease ,Kaplan-Meier Estimate ,Disease-Free Survival ,Antibodies, Monoclonal, Murine-Derived ,Young Adult ,Recurrence ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Aged ,Aged, 80 and over ,Clinical Trials as Topic ,End point ,business.industry ,Event free survival ,External validation ,ORIGINAL REPORTS ,Middle Aged ,medicine.disease ,Lymphoma ,Surgery ,Clinical trial ,Case-Control Studies ,Cohort ,Female ,Lymphoma, Large B-Cell, Diffuse ,business ,Rituximab ,Diffuse large B-cell lymphoma - Abstract
Purpose Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. Patients and Methods Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. Results In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. Conclusion Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.
- Published
- 2014
41. High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H
- Author
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Benet Nomdedeu, Deepti Radia, Fiona Clark, Geir E. Tjønnfjord, Estella Matutes, Vasantha Brito-Babapulle, Daniel Catovsky, Pietro Leoni, Claire Dearden, Antonio Parreira, Bruno Cazin, Martin J. S. Dyer, Tony Roques, Saad M. B. Rassam, and Nicolas Ketterer
- Subjects
Adult ,Male ,medicine.medical_specialty ,Antibodies, Neoplasm ,medicine.medical_treatment ,Immunology ,Antineoplastic Agents ,Hematopoietic stem cell transplantation ,Antibodies, Monoclonal, Humanized ,Biochemistry ,Immunophenotyping ,Leukemia, Prolymphocytic ,medicine ,Humans ,Transplantation, Homologous ,Pentostatin ,Prolymphocytic leukemia ,Alemtuzumab ,Survival rate ,Aged ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Cell Biology ,Hematology ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Surgery ,Survival Rate ,Transplantation ,Leukemia ,Cytogenetic Analysis ,Leukemia, Prolymphocytic, T-Cell ,T-cell prolymphocytic leukemia ,Female ,business ,medicine.drug - Abstract
T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-resistant malignancy with a median survival of 7.5 months. Preliminary results indicated a high remission induction rate with the human CD52 antibody, CAMPATH-1H. This study reports results in 39 patients with T-PLL treated with CAMPATH-1H between March 1993 and May 2000. All but 2 patients had received prior therapy with a variety of agents, including 30 with pentostatin; none achieved complete remission (CR). CAMPATH-1H (30 mg) was administered intravenously 3 times weekly until maximal response. The overall response rate was 76% with 60% CR and 16% partial remission (PR). These responses were durable with a median disease-free interval of 7 months (range, 4-45 months). Survival was significantly prolonged in patients achieving CR compared to PR or no response (NR), including one patient who survived 54 months. Nine patients remain alive up to 29 months after completing therapy. Seven patients received high-dose therapy with autologous stem cell support, 3 of whom remain alive in CR 5, 7, and 15 months after autograft. Stem cell harvests in these patients were uncontaminated with T-PLL cells as demonstrated by dual-color flow cytometry and polymerase chain reaction. Four patients had allogeneic stem cell transplants, 3 from siblings and 1 from a matched unrelated donor. Two had nonmyeloablative conditioning. Three are alive in CR up to 24 months after allograft. The conclusion is that CAMPATH-1H is an effective therapy in T-PLL, producing remissions in more than two thirds of patients. The use of stem cell transplantation to consolidate responses merits further study.
- Published
- 2001
42. Integrated Analysis of IGHV Gene Status, Cell-of-Origin Signature and Genomic Features in Diffuse Large B-Cell Lymphoma
- Author
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Bettina Fabiani, Corinne Haioun, Pierre-Julien Viailly, André Marc, Philippe Bertrand, Elodie Bohers, Sydney Dubois, Jean-Philippe Jais, Hervé Tilly, Freda K. Stevenson, Thierry Jo Molina, Christiane Copie-Bergman, Martin Figeac, Gilles Salles, Bruno Tesson, Philippe Ruminy, Frederic Peyrade, Catherine Maingonnat, Fabrice Jardin, Jean-Michel Picquenot, Karen Leroy, Thierry Fest, Pascaline Etancelin, Nicolas Ketterer, Thierry Lamy, Pauline Peyrouze, Sylvain Mareschal, and Richard Delarue
- Subjects
Oncology ,Genetics ,medicine.medical_specialty ,Immunology ,Somatic hypermutation ,Germinal center ,Cell Biology ,Hematology ,Biology ,CD79B ,medicine.disease ,Biochemistry ,GNA13 ,Lymphoma ,Germline mutation ,hemic and lymphatic diseases ,Internal medicine ,medicine ,IGHV@ ,Diffuse large B-cell lymphoma - Abstract
The molecular heterogeneity of diffuse large B-cell lymphoma (DLBCL) has been highlighted by gene expression profiling (GEP), dividing DLBCL into the following three main molecular subtypes with different clinical outcomes and responses to immunochemotherapy: the germinal center B-cell-like (GCB) subtype, the activated B-cell-like (ABC) subtype and the primary mediastinal B-cell lymphoma (PMBL) subtype. Despite frequent translocations involving the IGH (heavy chain) locus, B-cell receptor (BCR) expression is retained in almost all DLBCL, indicating that BCR signaling is crucial for the survival of malignant cells. Furthermore, DLBCL are characterized by recurrent somatic mutations that are supposed to be oncogenic drivers. Here, with the aim to more accurately define the DLBCL pathogenic subgroups, we report a detailed immunogenetic analysis of IGH rearrangements in a well-defined GEP DLBCL cohort and correlate these features with the somatic mutation status of recurrently mutated genes involved in lymphomagenesis. Methods: 204 DLBCL enrolled in the prospective LYSA LNH03 trial program were classified into molecular subtypes by GEP using Affymetrix arrays [82 ABC (40.2%), 77 GCB (37.7%), 29 (14.2%) unclassified and 16 PMBL (7.8%)]. The amplification of complete VDJ rearrangements was realized using BIOMED-2 protocols. Somatic hypermutation (SHM) characteristics were studied (mutation rate, glycosylation N-X-S/T sites, RGYW hotspots, composition of CDR3) and correlated with the molecular subtypes. To obtain a more comprehensive molecular portrait of the DLBCL cases, GEP and IGH VDJ analyses were correlated with the mutational status of a panel of 34 recurrently mutated genes in DLBCL such as MYD88, EZH2, CD79B, TNFAIP3, CARD11 and GNA13 (Dubois et al. Clinical Cancer Research 2016). Results: A total of 153/204 (75%) clonal VDJ rearrangements were successfully determined. Failures to detect clonotypic sequences were predominantly seen in PMBL (56%) and unclassified (31%) cases. The ABC subtype display a significantly lower SHM rate than the 3 other subtypes, especially in contrast to the PMBL subgroup that was characterized by a higher SHM rate (p Disclosures Haioun: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Salles:Mundipharma: Honoraria; Janssen: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria, Research Funding.
- Published
- 2016
43. Is Cisplatin Required for the Treatment of Non-Small-Cell Lung Cancer? Experience and Preliminary Results of a Phase I/II Trial with Topotecan and Vinorelbine
- Author
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Nicolas Ketterer, J. Bauer, Roger Stupp, Mohamed Bakr, Bertrand Duvoisin, Lucien Perey, Serge Leyvraz, and Alexandre Bodmer
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Vinblastine ,Vinorelbine ,Sensitivity and Specificity ,Drug Administration Schedule ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Infusions, Intravenous ,Lung cancer ,Aged ,Neoplasm Staging ,Chemotherapy ,Dose-Response Relationship, Drug ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Gemcitabine ,Surgery ,Survival Rate ,Irinotecan ,Regimen ,Treatment Outcome ,Docetaxel ,Female ,Topotecan ,Cisplatin ,business ,Follow-Up Studies ,medicine.drug - Abstract
Platinum-based chemotherapy is considered standard treatment for advanced non-small-cell lung cancer (NSCLC). However, toxicity of most platinum-based regimens is substantial and requires close monitoring and supportive care. Over the past decade, paclitaxel, docetaxel, vinorelbine, gemcitabine, irinotecan, and topotecan have been introduced into the clinic. These newer agents have shown promising activity against NSCLC with a favorable toxicity profile as single agents. For patients with metastatic NSCLC, palliation is the main goal of therapy. Therefore, treatment should be easy to administer on an outpatient basis. We explored a novel combination therapy avoiding platinum. Patients with recurrent or metastatic NSCLC were treated with intravenous (i.v.) topotecan (0.5–1.0 mg/m2/day × 5) and i.v. vinorelbine (20–30 mg/m2/day on day 1 and day 5) in 21-day cycles. Dose-limiting toxicity (DLT) was defined separately with or without the addition of granulocyte colony-stimulating factor (G-CSF) support. Twenty-nine patients have been enrolled to date. At i.v. topotecan doses of 0.75–1.0 mg/m2/day and i.v. vinorelbine of 25 mg/m2/day, neutropenia was frequent but of short duration (2) in the absence of G-CSF support was based on myelosuppression with neutropenic fever. With the addition of G-CSF, a DLT has not been reached. Nonhematologic toxicities included mild to moderate fatigue and constipation. An overall clinical response rate of 42% was achieved, with responses noted at all dose levels. At a short median follow-up of 15 months, the median survival for all patients is 13 months. In conclusion, the combination regimen of topotecan and vinorelbine is feasible for outpatient administration and is well tolerated with less toxicity than platinum-based regimens. Preliminary response data demonstrate good tumor activity, suggesting that this regimen could make an excellent palliative treatment for advanced NSCLC.
- Published
- 2001
44. Reduced progression-free survival in elderly patients receiving intensification with autologous peripheral blood stem cell reinfusion for multiple myeloma
- Author
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EM Neidhardt, Gilles Salles, Catherine Thieblemont, Daniel Espinouse, B. Coiffier, Charles Dumontet, I Moullet, and Nicolas Ketterer
- Subjects
Adult ,Male ,Melphalan ,medicine.medical_specialty ,medicine.medical_treatment ,Transplantation, Autologous ,Immunopathology ,Humans ,Medicine ,Progression-free survival ,Multiple myeloma ,Aged ,Transplantation ,Chemotherapy ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Total body irradiation ,medicine.disease ,Surgery ,Survival Rate ,Prior Therapy ,Female ,Stem cell ,Multiple Myeloma ,business ,medicine.drug - Abstract
Between 1990 and 1997, 55 patients with high risk multiple myeloma underwent high-dose therapy with peripheral blood stem cell transplantation. Intensification consisted of high-dose L-PAM in 54 patients, and 15 patients underwent a second high-dose treatment. Thirty patients received total body irradiation. Twenty patients were more than 60 years old. Thirty-five patients were intensified during first response. The overall response rate was 78%. There were four toxic deaths. The median overall survivals after intensification and after first treatment of myeloma were greater than 48 months and 71 months, respectively. Conversely freedom from progression after intensification was short, with a median of 22 months. Freedom from progression was significantly shorter in patients older than 60 (12 months), and in patients who had received more than 75 mg/m2 of L-PAM before intensification (16 months). Although intensification is feasible in elderly patients the benefit appears to be reduced in this subgroup of patients. Prior therapy with high cumulative doses of L-PAM should be avoided in patients who will receive high-dose L-PAM for therapeutic intensification.
- Published
- 1998
45. Improving the chance of cure of follicular lymphoma by combining immunotherapy and radioimmunotherapy based on anti-CD20 antibodies?
- Author
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Jean-Pierre Mach, Franz Buchegger, Oliver W. Press, Nicolas Ketterer, John O. Prior, Steven M. Larson, and A. Bischof Delaloye
- Subjects
medicine.medical_specialty ,animal structures ,medicine.medical_treatment ,Follicular lymphoma ,Left Ventricular Ejection Time ,Special Article ,Anti cd20 antibody ,Internal medicine ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Letters to the Editor ,Lymphoma, Follicular ,Neoplasm Staging ,business.industry ,Disease Management ,Hematology ,Immunotherapy ,medicine.disease ,Combined Modality Therapy ,Leukemia, Lymphocytic, Chronic, B-Cell ,ESTIMATED GESTATIONAL AGE ,medicine.anatomical_structure ,Oncology ,Systolic time intervals ,Radioimmunotherapy ,Positron-Emission Tomography ,Practice Guidelines as Topic ,Vascular resistance ,Cardiology ,Lymphoma, Large B-Cell, Diffuse ,Leukemia, Lymphocytic, Chronic, B-Cell/therapy ,Lymphoma, Follicular/radiotherapy ,Lymphoma, Large B-Cell, Diffuse/drug therapy ,business ,Stem Cell Transplantation - Abstract
To complete the existing treatment guidelines for all tumor types, ESMO organizes consensus conferences to better clarify open issues in each disease. In this setting, a consensus conference on the management of lymphoma was held on 18 June 2011 in Lugano, immediately after the end of the 11th International Conference on Malignant Lymphoma. The consensus conference convened ∼45 experts from all around Europe and selected six lymphoma entities to be addressed; for each of them three to five open questions were to be discussed by the experts. For each question, a recommendation should be given by the panel, supported by the strength of the recommendation based on the level of evidence. This consensus report focuses on the three most common lymphoproliferative malignancies: diffuse large B-cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia. A second report will concentrate on mantle cell lymphoma, marginal zone lymphoma and T-cell lymphomas.
- Published
- 2013
46. Immunoglobulin heavy chain/light chain pair measurement is associated with survival in diffuse large B-cell lymphoma
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Frederic Peyrade, Danielle Canioni, Karen Leroy, Hervé Tilly, Gilles Salles, Martin Figeac, Nicolas Ketterer, Jean-Philippe Jais, André Bosly, Christiane Copie-Bergman, Thierry Jo Molina, Fabrice Jardin, Bertrand Coiffier, Marc André, Richard Delarue, Bettina Fabiani, Corinne Haioun, Marie Hélène Delfau-Larue, Josette Brière, Sylvain Mareschal, and Tony Petrella
- Subjects
Adult ,Male ,Cancer Research ,Vincristine ,Pathology ,medicine.medical_specialty ,Immunoglobulin light chain ,Gastroenterology ,Antibodies, Monoclonal, Murine-Derived ,International Prognostic Index ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Cyclophosphamide ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,business.industry ,Hazard ratio ,Hematology ,Middle Aged ,medicine.disease ,Prognosis ,Lymphoma ,Immunoglobulin Isotypes ,Oncology ,Doxorubicin ,Immunoglobulin heavy chain ,Prednisone ,Rituximab ,Female ,Immunoglobulin Light Chains ,Lymphoma, Large B-Cell, Diffuse ,business ,Immunoglobulin Heavy Chains ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
Elevated serum free light chains (FLCs) have been associated with an unfavorable prognosis in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to determine the clinical relevance of a quantitative assessment of intact circulating immunoglobulin (Ig), using serum Ig heavy chain/light chain pair (HLC) measurements in patients with DLBCL. FLC and HLC were measured in 409 serum samples of patients with DLBCL included in the LNH03-B clinical trial program of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA). Patients with an abnormal IgMκ/IgMλ ratio or an abnormal FLC ratio more frequently displayed adverse clinical characteristics. Patients with abnormal IgMκ/IgMλ ratios had inferior progression-free survival (PFS) and overall survival (OS) as compared to patients with a normal ratio in the overall cohort (5-year PFS 44.9% vs. 69.3%, p = 0.0003 and 5-year OS 50.8% vs. 78.1%, p = 0.0003) and in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) cohort (5-year OS 43.5% vs. 70.3%, p = 0.003). In multivariate analysis, including elevated FLC/HLC and International Prognostic Index (IPI), an abnormal IgMκ/IgMλ ratio (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.03-2.3, p = 0.03) remained predictive of shorter progression-free survival. Gene expression profile experiments and immunohistochemistry indicate that this measurement is at least partially related to tumor cell secretion. Both elevated serum FLCs and an abnormal IgMκ/IgMλ ratio are associated with unfavorable outcomes in patients with DLBCL treated by R-CHOP.
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- 2013
47. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1b)
- Author
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Corinne Haioun, Richard Delarue, F. Morschhauser, Serge Bologna, Christophe Fermé, Christophe Bonnet, B. Christian, Olivier Casasnovas, Christophe Fruchart, Bruno Anglaret, Nicolas Ketterer, Bertrand Coiffier, Hervé Tilly, Carole Soussain, Christian Recher, Thierry Connerotte, Josette Brière, Catherine Thieblemont, Bettina Fabiani, Dominique Bordessoule, and UCL - (SLuc) Service d'hématologie
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Adolescent ,Drug-Related Side Effects and Adverse Reactions ,Vindesine ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Disease-Free Survival ,Antibodies, Monoclonal, Murine-Derived ,Bleomycin ,International Prognostic Index ,Prednisone ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Progression-free survival ,Cyclophosphamide ,Aged ,Neoplasm Staging ,Chemotherapy ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Chemotherapy regimen ,Surgery ,Treatment Outcome ,Doxorubicin ,Female ,Rituximab ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
Background: The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which evaluates the role of rituximab combined with ACVBP (R-ACVBP) in these patients. Patients and methods: Untreated patients younger than 66 years with stage I or II DLBCL and no adverse prognostic factors of the age-adjusted International Prognostic Index were randomly assigned to receive three cycles of ACVBP plus sequential consolidation with or without the addition of four infusions of rituximab. Results: A total of 223 patients were randomly allocated to the study, 110 in the R-ACVBP group and 113 in the ACVBP group. After a median follow-up of 43 months, our 3-year estimate of event-free survival was 93 in the R-ACVBP group and 82 in the ACVBP group (P 0.0487). Three-year estimate of progression-free survival was increased in the R-ACVBP group (95 versus 83, P 0.0205). Overall survival did not differ between the two groups with a 3-year estimates of 98 and 97, respectively (P 0.686). Conclusion: In young patients with low-risk localized DLBCL, rituximab combined with three cycles of ACVBP plus consolidation is significantly superior to ACVBP plus consolidation alone. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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- 2013
48. Intensification of chemotherapy for the treatment of solid tumours: feasibility of a 3-fold increase in dose intensity with peripheral blood progenitor cells and granulocyte colony-stimulating factor
- Author
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L Perey, Ferdy J. Lejeune, V. von Fliedner, Fedor Bachmann, JPh Grob, Ph. Schneider, P. Vuichard, J. Bauer, Nicolas Ketterer, and Serge Leyvraz
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Cyclophosphamide ,medicine.medical_treatment ,Cell Separation ,Filgrastim ,Gastroenterology ,Neoplasms ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Granulocyte Colony-Stimulating Factor ,medicine ,Humans ,Etoposide ,Chemotherapy ,Dose-Response Relationship, Drug ,business.industry ,Hematopoietic Stem Cell Transplantation ,Combination chemotherapy ,Middle Aged ,Surgery ,Granulocyte colony-stimulating factor ,Transplantation ,Regimen ,Oncology ,Female ,business ,Research Article ,medicine.drug - Abstract
Dose intensity may be an important determinant of the outcome in cancer chemotherapy, but is often limited by cumulative haematological toxicity. The availability of haematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and of peripheral blood progenitor cell (PBPC) transplantation has allowed the development of a new treatment strategy in which several courses of high-dose combination chemotherapy are administered for the treatment of solid tumours. PBPCs were mobilised before chemotherapy using 12 or 30 micrograms kg-1 day-1 G-CSF (Filgrastim) for 10 days, and were collected by 2-5 leucaphereses. The yields of mononuclear cells, colony-forming units and CD34-positive cells were similar at the two dose levels of Filgrastim, and the numbers of PBPCs were sufficient for rescue following multiple cycles of chemotherapy. High-dose chemotherapy (cyclophosphamide 2.5 g m-2 for 2 days, etoposide 300 mg m-2 for 3 days and cisplatin 50 mg m-2 for 3 days) was administered sequentially for a median of three cycles (range 1-4) to ten patients. Following the 30 evaluable cycles, the median duration of leucopenia < or = 0.5 x 10(9) l-1 and < or = 1.0 x 10(9) l-1 was 7 and 8 days respectively. The median time of thrombopenia < or = 20 x 10(9) l-1 was 6 days. There was no cumulative haematological toxicity. The duration of leucopenia, but not of thrombopenia, was inversely related to the number of reinfused CFU-GM (granulocyte-macrophage colony-forming units). In the majority of patients, neurotoxicity and ototoxicity became dose limiting after three cycles of therapy. However, the average dose intensity delivered was about three times higher than in a standard regimen. The complete response rate in patients with small-cell lung cancers was 66% (95% CI 30-92%) and the median progression-free survival and overall survival were 13 months and 17 months respectively. These results are encouraging and should be compared, in a randomised fashion, with standard dose chemotherapy.
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- 1995
49. Rituximab Maintenance Therapy After Autologous Stem-Cell Transplantation in Patients With Relapsed CD20+ Diffuse Large B-Cell Lymphoma: Final Analysis of the Collaborative Trial in Relapsed Aggressive Lymphoma
- Author
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Noel Milpied, David C. Linch, John Radford, Andreas Viardot, Ray M. Lowenthal, Craig H. Moskowitz, Hans Hagberg, Norbert Schmitz, Marek Trneny, André Bosly, Ofer Shpilberg, Nicolas Ketterer, Ulrich Dührsen, Nicolas Mounier, Christian Gisselbrecht, David D.F. Ma, Gilles Salles, Devinder Gill, Bertram Glass, and Josette Brière
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Medizin ,Salvage therapy ,Aggressive lymphoma ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,Maintenance Chemotherapy ,Antibodies, Monoclonal, Murine-Derived ,Young Adult ,Autologous stem-cell transplantation ,Maintenance therapy ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Original Reports ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Aged ,Salvage Therapy ,business.industry ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,medicine.disease ,Antigens, CD20 ,Combined Modality Therapy ,Survival Analysis ,Surgery ,Transplantation ,Disease Progression ,Rituximab ,Female ,Lymphoma, Large B-Cell, Diffuse ,business ,Diffuse large B-cell lymphoma ,medicine.drug - Abstract
Purpose The standard treatment for relapsed diffuse large B-cell lymphoma (DLBCL) is salvage chemotherapy followed by high-dose therapy and autologous stem-cell transplantation (ASCT). The impact of maintenance rituximab after ASCT is not known. Patients and Methods In total, 477 patients with CD20+ DLBCL who were in their first relapse or refractory to initial therapy were randomly assigned to one of two salvage regimens. After three cycles of salvage chemotherapy, the responding patients received high-dose chemotherapy followed by ASCT. Then, 242 patients were randomly assigned to either rituximab every 2 months for 1 year or observation. Results After ASCT, 122 patients received rituximab, and 120 patients were observed only. The median follow-up time was 44 months. The 4-year event-free survival (EFS) rates after ASCT were 52% and 53% for the rituximab and observation groups, respectively (P = .7). Treatment with rituximab was associated with a 15% attributable risk of serious adverse events after day 100, with more deaths (six deaths v three deaths in the observation arm). Several factors affected EFS after ASCT (P < .05), including relapsed disease within 12 months (EFS: 46% v 56% for relapsed disease after 12 months), secondary age-adjusted International Prognostic Index (saaIPI) more than 1 (EFS: 37% v 61% for saaIPI < 1), and prior treatment with rituximab (EFS: 47% v 59% for no prior rituximab). A significant difference in EFS between women (63%) and men (46%) was also observed in the rituximab group. In the Cox model for maintenance, the saaIPI was a significant prognostic factor (P < .001), as was male sex (P = .01). Conclusion In relapsed DLBCL, we observed no difference between the control group and the rituximab maintenance group and do not recommend rituximab after ASCT.
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- 2012
50. Longer intervals between hematopoietic stem cell transplantation and subsequent 90Y-ibritumomab radioimmunotherapy may correlate with better tolerance
- Author
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Marek Kosinski, Angelika Bischof Delaloye, Yves Chalandon, Franz Buchegger, Sébastien Baechler, Nicolas Ketterer, Osman Ratib, Claudine Helg, John O. Prior, and Gilles Allenbach
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Lymphoma ,medicine.medical_treatment ,Follicular lymphoma ,Hematopoietic stem cell transplantation ,Kaplan-Meier Estimate ,Antibodies, Monoclonal/adverse effects ,Transplantation, Homologous/adverse effects ,ddc:616.0757 ,Gastroenterology ,immune system diseases ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Medicine ,Humans ,Transplantation, Homologous ,Radiology, Nuclear Medicine and imaging ,Hematopoietic Stem Cell Transplantation/adverse effects ,Radioimmunotherapy/adverse effects ,Aged ,Retrospective Studies ,ddc:616 ,Lymphoma/radiotherapy/surgery ,business.industry ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,General Medicine ,Immunotherapy ,Middle Aged ,Radioimmunotherapy ,medicine.disease ,Surgery ,surgical procedures, operative ,medicine.anatomical_structure ,Toxicity ,Mantle cell lymphoma ,Female ,Bone marrow ,business - Abstract
PURPOSE: This study aimed to evaluate the efficacy and toxicity of radioimmunotherapy (RIT) in recurrent lymphoma after hematopoietic stem cell transplantation (HSCT). METHODS: We reviewed 9 patients, 7 with follicular lymphoma (DLBCL), 1 with mantle cell lymphoma (MCL), and 1 with diffuse large B-cell lymphoma treated with Y-ibritumomab tiuxetan 6 to 140 months after HSCT. Patients underwent In-ibritumomab scintigraphy and were treated 1 week later with standard 14.8 MBq/kg (n = 4) or 11.1 MBq/kg (n = 4) Y-ibritumomab. One patient who had allo-HSCT had reduced activity (70%) treatment. RESULTS: Among the 7 FL patients, we observed complete response (CR) in 2 patients and partial response (PR) in 5 patients. One patient with CR relapsed after 15 months; the other persisted 43.5 months after RIT. Of 5 patients with PR, 3 relapsed between 13 and 17 months; 1 persisted until unrelated death at 11.5 months. The fifth patient with PR received adoptive immunotherapy and improved to metabolic (FDG-PET) CR that persists 45.5 and 41 months after Y-ibritumomab and immunotherapy, respectively. Patients with MCL and DLBCL progressed or experienced stabilization (5 months), respectively. Six patients had grade 1 to 3 bone marrow (BM) toxicity and recovered within 3 months. Three patients having Y-ibritumomab 6, 14, and 24 months after HSCT experienced grade 4 BM toxicity. One of them (RIT 24 months after HSCT) recovered after 3 months, another delayed after 9 months, and the third patient only partially recovered, eventually developed myelodysplasia, and was allografted. CONCLUSIONS: Radioimmunotherapy after HSCT is an effective rescue therapy in FL. However, BM toxicity may be important; 3 of 8 patients treated with standard Y-ibritumomab activity experienced grade 4 BM toxicity, with incomplete recovery 3 months after RIT in 2 patients, both treated early (6 and 14 months) after HSCT.
- Published
- 2012
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