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1. Long‐term overall survival and toxicities of ABVD vs BEACOPP in advanced Hodgkin lymphoma: A pooled analysis of four randomized trials

Author

Marc P. E. André, Patrice Carde, Simonetta Viviani, Monica Bellei, Catherine Fortpied, Martin Hutchings, Alessandro M. Gianni, Pauline Brice, Olivier Casasnovas, Paolo G. Gobbi, Pier Luigi Zinzani, Jehan Dupuis, Emilio Iannitto, Alessandro Rambaldi, Josette Brière, Laurianne Clément‐Filliatre, Marian Heczko, Pinuccia Valagussa, Jonathan Douxfils, Julien Depaus, Massimo Federico, and Nicolas Mounier

Subjects
ABVD, BEACOPP, Hodgkin lymphoma, overall survival, progression‐free survival, secondary cancers, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Purpose We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials. Patients and methods Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression‐free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT). Results About 1227 patients were included. The 7‐year OS was 84.3% (95% CI 80.8‐87.2) for ABVD vs 87.7% (95% CI 84.5‐90.2) for BEACOPP. Two follow‐up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP = 1.59; 95% CI 1.09‐2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7‐year PFS was 71.1% (95% CI 67.1‐74.6) for ABVD vs 81.1% (95% CI 77.5‐84.2) for BEACOPP (P

Published
2020
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2. Brentuximab vedotin in refractory or relapsed peripheral T-cell lymphomas: the French named patient program experience in 56 patients

Author

Mathilde Lamarque, Céline Bossard, Adrien Contejean, Pauline Brice, Marie Parrens, Steven Le Gouill, Josette Brière, Reda Bouabdallah, Danielle Canioni, Hervé Tilly, Brigitte Bouchindhomme, Emmanuel Bachy, Richard Delarue, Corinne Haioun, and Philippe Gaulard

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2016
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3. Respective prognostic values of germinal center phenotype and early 18fluorodeoxyglucose-positron emission tomography scanning in previously untreated patients with diffuse large B-cell lymphoma

Author

Jehan Dupuis, Philippe Gaulard, Francois Hemery, Emmanuel Itti, Christian Gisselbrecht, Alain Rahmouni, Christiane Copie-Bergman, Josette Brière, Taoufik El Gnaoui, Isabelle Gaillard, Michel Meignan, and Corinne Haioun

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

Background and Objectives Diffuse large B-cell lymphomas (DLBCL) have a variable outcome, and powerful methods of prognostication are needed in order to choose the best treatment for each patient. Immunophenotypic classification of the tumor as germinal center (GC) or non-germinal center-like (nGC) and early response evaluation with 18fluorodeoxyglucose positron emission tomography (18FDG-PET) scanning have been correlated with survival in DLBCL but the two methods have never been evaluated simultaneously in the same patient population. Our aim was to investigate their respective prognostic values in the same series of patients.Design and Methods We investigated the expression of CD10, Bcl-6, and MUM1 in 81 patients with DLBCL evaluated early with 18FDG-PET. The tumors were classified as GC or nGC using the algorithm of Hans et al. The results of both methods were correlated with the patients’ characteristics and survival.Results CD10 was positive in 27/76 (36%), Bcl-6 in 43/74 (58%), and MUM1 in 33/73 (45%) interpretable cases. Thirty-eight (51%) were in the GC group, and 36 (49%) in the nGC group. With a median follow-up of 33 months, estimated 3-year event-free survival (EFS) of the whole population was 67%. There was no influence of GC/nGC phenotype on survival. Three-year EFS was 46% in the early PET-positive group versus 80% in the PET-negative group (p=0.0003).Interpretation and Conclusions The prognostic value of GC/nGC phenotype is not confirmed in this heterogeneous series, whereas early PET findings are confirmed to be a powerful predictor of outcome. The impact of treatment decisions based on early PET results should be evaluated.

Published
2007
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4. Association of killer cell immunoglobulin-like receptor genes with Hodgkin's lymphoma in a familial study.

Author

Caroline Besson, Sophie Roetynck, Fionnuala Williams, Laurent Orsi, Corinne Amiel, Catherine Lependeven, Guillemette Antoni, Olivier Hermine, Pauline Brice, Christophe Ferme, Patrice Carde, Danielle Canioni, Josette Brière, Martine Raphael, Jean-Claude Nicolas, Jacqueline Clavel, Derek Middleton, Eric Vivier, and Laurent Abel

Subjects
Medicine, Science
Abstract

BackgroundEpstein-Barr virus (EBV) is the major environmental factor associated with Hodgkin's lymphoma (HL), a common lymphoma in young adults. Natural killer (NK) cells are key actors of the innate immune response against viruses. The regulation of NK cell function involves activating and inhibitory Killer cell Immunoglobulin-like receptors (KIRs), which are expressed in variable numbers on NK cells. Various viral and virus-related malignant disorders have been associated with the presence/absence of certain KIR genes in case/control studies. We investigated the role of the KIR cluster in HL in a family-based association study.MethodologyWe included 90 families with 90 HL index cases (age 16-35 years) and 255 first-degree relatives (parents and siblings). We developed a procedure for reconstructing full genotypic information (number of gene copies) at each KIR locus from the standard KIR gene content. Out of the 90 collected families, 84 were informative and suitable for further analysis. An association study was then carried out with specific family-based analysis methods on these 84 families.Principal findingsFive KIR genes in strong linkage disequilibrium were found significantly associated with HL. Refined haplotype analysis showed that the association was supported by a dominant protective effect of KIR3DS1 and/or KIR2DS1, both of which are activating receptors. The odds ratios for developing HL in subjects with at least one copy of KIR3DS1 or KIR2DS1 with respect to subjects with neither of these genes were 0.44[95% confidence interval 0.23-0.85] and 0.42[0.21-0.85], respectively. No significant association was found in a tentative replication case/control study of 68 HL cases (age 18-71 years). In the familial study, the protective effect of KIR3DS1/KIR2DS1 tended to be stronger in HL patients with detectable EBV in blood or tumour cells.ConclusionsThis work defines a template for family-based association studies based on full genotypic information for the KIR cluster, and provides the first evidence that activating KIRs can have a protective role in HL.

Published
2007
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5. Supplementary Data from Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study

Author

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

Abstract

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

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

Author

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

Abstract

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

Published
2023
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7. Obinutuzumab vs rituximab for advanced DLBCL: a PET-guided and randomized phase 3 study by LYSA

Author

Gandhi Damaj, Steven Le Gouill, Christophe Bonnet, Hervé Ghesquières, David Sibon, Marc André, Emmanuel Itti, Loïc Chartier, Françoise Kraeber-Bodéré, Luc Fornecker, Hervé Tilly, Vincent Ribrag, Franck Morschhauser, Jean-Philippe Jais, Caroline Bodet-Milin, Alina Berriolo-Riedinger, Krimo Bouhabdallah, Philippe Ruminy, Guillaume Cartron, Catherine Thieblemont, Remy Gressin, Reda Bouhabdallah, Corinne Haioun, Lucie Oberic, Thierry Jo Molina, René-Olivier Casasnovas, Pierre Feugier, Josette Brière, Thierry Lamy, and Hervé Maisonneuve

Subjects
medicine.medical_specialty, Immunology, CHOP, Antibodies, Monoclonal, Humanized, Biochemistry, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, International Prognostic Index, Obinutuzumab, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Cyclophosphamide, business.industry, Cell Biology, Hematology, medicine.disease, Chemotherapy regimen, 3. Good health, Transplantation, chemistry, Doxorubicin, Vincristine, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Prednisone, Vindesine, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, 030215 immunology, medicine.drug
Abstract

Rituximab plus polychemotherapy is the standard of care in diffuse large B-cell lymphoma (DLBCL). GAINED, a randomized phase 3 trial, compared obinutuzumab to rituximab. Transplant-eligible patients (18-60 years) with an untreated age-adjusted International Prognostic Index (aaIPI) score ≥1 DLBCL were randomized (1:1) between obinutuzumab or rituximab and stratified by aaIPI (1; 2-3) and chemotherapy regimen (doxorubicin, cyclophosphamide, prednisone plus vindesine, bleomycin [ACVBP] or vincristine [CHOP]). Consolidation treatment was determined according to response to interim positron emission tomography (PET). Responders after cycle 2 and 4 (PET2−/PET4−) received immunochemotherapy. Responders after only cycle 4 (PET2+/4−) received transplantation. The primary objective was an 8% improvement (hazard ratio [HR] = 0.73; 80% power; α risk, 2.5%; 1-sided) in 2-year event-free survival (EFS) in the obinutuzumab arm. From September 2012, 670 patients were enrolled (obinutuzumab, n = 336; rituximab, n = 334). A total of 383 (57.2%) were aaIPI 2-3, 339 (50.6%) received CHOP. Median follow-up was 38.7 months. The 2-year EFS was similar in both groups (59.8% vs 56.6%; P = .123; HR = 0.88). The 2-year PFS in the whole cohort was 83.1% (95% confidence interval, 80% to 85.8%). PET2−/4− and PET2+/4− had similar 2-year progression-free survival (PFS) and overall survival (OS): 89.9% vs 83.9% and 94.8% vs 92.8%. The 2-year PFS and OS for PET4+ patients were 62% and 83.1%. Grade 3-5 infections were more frequent in the obinutuzumab arm (21% vs 12%). Obinutuzumab is not superior to rituximab in aaIPI ≥1 DLBCL transplant-eligible patients. This trial was registered at www.clinicaltrials.gov as #NCT01659099.

Published
2021
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8. High total metabolic tumor volume at baseline predicts survival independent of response to therapy

Author

Julie Abraham, Marc Simon, Hervé Tilly, Josette Brière, Anne-Ségolène Cottereau, Lucie Oberic, Michel Meignan, Olivier Casasnovas, Olivier Fitoussi, Pascal Godmer, Christophe Fruchart, Laurence Sanhes, Laetitia Vercellino, Gian Matteo Pica, Pierre Feugier, Gilles Salles, Vincent Ribrag, Catherine Thieblemont, Armando López-Guillermo, Judith Trotman, Bernadette Corront, Loïc Chartier, Hugo Gonzalez, Franck Morschhauser, Philippe Gaulard, Bachra Choufi, Catherine Sebban, L. Roulin, Reda Bouabdallah, and Sylvia Snauwaert

Subjects
Male, Oncology, Vincristine, medicine.medical_specialty, Immunology, Population, Angiogenesis Inhibitors, Standardized uptake value, Biochemistry, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, Prednisone, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Stage (cooking), education, Cyclophosphamide, Lenalidomide, neoplasms, Aged, Aged, 80 and over, education.field_of_study, business.industry, Cell Biology, Hematology, Middle Aged, Prognosis, Tumor Burden, Doxorubicin, 030220 oncology & carcinogenesis, Female, Rituximab, Lymphoma, Large B-Cell, Diffuse, business, medicine.drug
Abstract

Early identification of ultra-risk diffuse large B-cell lymphoma (DLBCL) patients is needed to aid stratification to innovative treatment. Previous studies suggested high baseline total metabolic tumor volume (TMTV) negatively impacts survival of DLBCL patients. We analyzed the prognostic impact of TMTV and prognostic indices in DLBCL patients, aged 60 to 80 years, from the phase 3 REMARC study that randomized responding patients to R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) into maintenance lenalidomide or placebo. TMTV was computed on baseline positron emission tomography/computed tomography using the 41% maximum standardized uptake value method; the optimal TMTV cutoff for progression-free (PFS) and overall survival (OS) was determined and confirmed by a training validation method. There were 301 out of 650 evaluable patients, including 192 patients classified as germinal center B-cell–like (GCB)/non-GCB and MYC/BCL2 expressor. Median baseline TMTV was 238 cm3; optimal TMTV cutoff was 220 cm3. Patients with high vs low TMTV showed worse/higher Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, stage III or IV disease, >1 extranodal site, elevated lactate dehydrogenase, International Prognostic Index (IPI) 3-5, and age-adjusted IPI 2-3. High vs low TMTV significantly impacted PFS and OS, independent of maintenance treatment. Although the GCB/non-GCB profile and MYC expression did not correlate with TMTV/survival, BCL2 >70% impacted PFS and could be stratified by TMTV. Multivariate analysis identified baseline TMTV and ECOG PS as independently associated with PFS and OS. Even in responding patients, after R-CHOP, high baseline TMTV was a strong prognosticator of inferior PFS and OS. Moreover, TMTV combined with ECOG PS may identify an ultra-risk DLBCL population. This trial was registered at www.clinicaltrials.gov as #NCT01122472.

Published
2020
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9. EARLY POSITRON EMISSION TOMOGRAPHY RESPONSE‐ADAPTED TREATMENT IN LOCALIZED DIFFUSE LARGE B‐CELL LYMPHOMA (AAIPI=0) : RESULTS OF THE PHASE 3 LYSA LNH 09‐1B TRIAL

Author

Ghandi Damaj, Christophe Bonnet, T. Vander Borght, Diane Coso, Serge Bologna, Laure Lebras, Frederic Peyrade, J. N Bastie, Pierre Olivier, David Sibon, B. Fabiani, Herve Ghesquieres, Catherine Thieblemont, F. Morschhauser, Stéphanie Becker, Vincent Ribrag, H. Tilly, Josette Brière, P. Feugier, and Corinne Haioun

Subjects
Cancer Research, Materials science, Nuclear magnetic resonance, Oncology, medicine.diagnostic_test, Positron emission tomography, Phase (matter), medicine, Hematology, General Medicine, medicine.disease, Diffuse large B-cell lymphoma
Published
2021
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10. Lymphome à cellules du manteau : une entité très hétérogène sur le plan histopathologique et pronostique

Author

Josette Brière, Edouard Guenzi, Danielle Canioni, Thierry Molina, and Julie Bruneau

Subjects
03 medical and health sciences, Medical Laboratory Technology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Biochemistry (medical), 030204 cardiovascular system & hematology, Analytical Chemistry
Abstract

Resume La classification OMS 2016 identifie clairement deux variantes du lymphome a cellules du manteau : une variante classique et une variante indolente. L’identification de ces variantes qui presentent des caracteristiques cliniques, histologiques, phenotypiques et moleculaires differentes est importante car elle conditionne la prise en charge therapeutique pouvant aller d’une surveillance a une chimiotherapie lourde. Le pathologiste doit etre familier avec ces deux variantes dont l’ontogenie est supposee differente mais qui parfois restent de diagnostic differentiel difficile. Le pathologiste doit etre egalement conscient de l’extreme variabilite cytologique et phenotypique de ce lymphome qui peut mimer tous les autres types histologiques de lymphome B et pour lequel la detection d’une hyperexpression de la cycline D1, de SOX 11 et la mise en evidence de la translocation t (11 ;14) (q13; q32) sont des elements majeurs du diagnostic.

Published
2019
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11. VEGF121, is predictor for survival in activated B-cell-like diffuse large B-cell lymphoma and is related to an immune response gene signature conserved in cancers

Author

Rémi Houlgatte, Josette Brière, Sophie Bernard, Catherine Thieblemont, Wendy Cuccuini, Gérard Ramstein, Philippe Gaulard, Christian Gisselbrecht, Julien Broséus, Nicolas Mounier, and Samia Mourah

Subjects
0301 basic medicine, Oncology, Gerontology, medicine.medical_specialty, Aggressive lymphoma, immune response, angiogenesis, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Internal medicine, medicine, cancer, like DLBCL, Tumor microenvironment, Immune response gene, Hematology, business.industry, Gene signature, medicine.disease, 3. Good health, Lymphoma, 030104 developmental biology, Tumor progression, 030220 oncology & carcinogenesis, business, ABC, Diffuse large B-cell lymphoma, Research Paper
Abstract

// Julien Broseus 1,2,* , Samia Mourah 3,4,5,* , Gerard Ramstein 6 , Sophie Bernard 7 , Nicolas Mounier 8 , Wendy Cuccuini 9 , Philippe Gaulard 10,11 , Christian Gisselbrecht 7,12 , Josette Briere 13 , Remi Houlgatte 1,14,** and Catherine Thieblemont 3,7 1 Inserm U954, Faculty of Medicine, University of Lorraine, Nancy, France 2 University Hospital of Nancy, Hematology Laboratory, Nancy, France 3 Paris Diderot University, Sorbonne Paris Cite, Paris, France 4 APHP, Saint Louis University Hospital, Pharmacology-Biologic Laboratory, Paris, France 5 Inserm UMRS 976, France 6 LS2N - DUKe, University of Nantes, Nantes, France 7 APHP, Saint-Louis University Hospital, Hemato-Oncology, Paris, France 8 University Hospital of L’archet, Nice, France 9 APHP, Saint-Louis University Hospital, Hematology Laboratory, Paris, France 10 Department of Pathology, APHP, Henri Mondor University Hospital, Creteil, France 11 Inserm U955, University Paris-Est, Creteil, France 12 Lymphoma Study Association, Pierre-Benite, France 13 Department of Pathology, APHP, Saint-Louis University Hospital, Paris, France 14 University Hospital of Nancy, DRCI, Nancy, France * Julien Broseus and Samia Mourah have contributed equally to this work ** Catherine Thieblemont and Remi Houlgatte have contributed equally to this work Correspondence to: Catherine Thieblemont, email: // Remi Houlgatte, email: // Keywords : ABC, like DLBCL, angiogenesis, immune response, cancer Received : June 12, 2017 Accepted : July 03, 2017 Published : July 19, 2017 Abstract Tumor microenvironment including endothelial and immune cells plays a crucial role in tumor progression and has been shown to dramatically influence cancer survival. In this study, we investigated the clinical relevance of the gene expression of key mediators of angiogenesis, VEGF isoforms 121, 165, and 189, and their receptors (VEGFR-1 and R-2) in a cohort of patients ( n = 37) with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) from the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL). In patients with ABC-like DLBCL, but not in patients with GCB-like DLBCL, low VEGF 121 expression was associated with a significantly better survival than in those with high VEGF 121 level: 4-year overall survival at 100% vs 36% ( p = .011), respectively. A specific gene signature including 57 genes was correlated to VEGF 121 expression level and was analyzed using a discovery process in 1,842 GSE datasets of public microarray studies. This gene signature was significantly expressed in other cancer datasets and was associated with immune response. In conclusion, low VEGF 121 expression level was significantly associated with a good prognosis in relapsed/refractory ABC-like DLBCL, and with a well-conserved gene-expression profiling signature related to immune response. These findings pave the way for rationalization of drugs targeting immune response in refractory/relapsed ABC-like DLBCL.

Published
2017
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12. GAPDH Expression Predicts the Response to R-CHOP, the Tumor Metabolic Status, and the Response of DLBCL Patients to Metabolic Inhibitors

Author

Vincent Delwail, Jean-Ehrland Ricci, Isabelle Peyrottes, Celine Delpech-Debiais, Sandrine Marchetti, Julie Reverso-Meinietti, Jacqueline Lehmann-Che, Gabriel Brisou, Jozef P. Bossowski, Manuel Grima-Reyes, Christiane Copie-Bergman, Camila Rubio-Patiño, Konstantina Fragaki, Eric de Kerviler, Véronique Paquis-Flucklinger, Thierry Jo Molina, Frederic Peyrade, Annabelle Mouchotte, Tony Petrella, Emma Proïcs, Bertrand Nadel, Els Verhoeyen, Bruno Taillan, Richard Delarue, Catherine Thieblemont, Laetitia Shintu, Agnès Paquet, Rana Mhaidly, Johanna Chiche, Elodie Villa, Georges Garnier, Pascal Barbry, Josette Brière, Damien Ambrosetti, Nicolas Mounier, André Bosly, Jean-François Michiels, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Pasteur [Nice] (CHU), Hôpital Hôtel Dieu, INSERM U955, équipe 9, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Department of Pathology, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA), UNICANCER-Université Côte d'Azur (UCA), Hôpital Princesse Grace [Monaco], Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Cliniques universitaires UCL de Mont-Godinne 5530 Yvoir, Centre de pathologie [Dijon], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Service hématologie Nice, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'onco-hématologie [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Physiopathologie de la survie et de la mort cellulaire et infection virale, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de pathologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Côte d'Azur (UCA), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), 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)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Antoine Lacassagne, Centre Antoine Lacassagne, Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Nice Sophia Antipolis (... - 2019) (UNS), UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne

Subjects
0301 basic medicine, Male, Physiology, Phenformin, Cohort Studies, chemistry.chemical_compound, Mice, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Glyceraldehyde 3-phosphate dehydrogenase, Cells, Cultured, Aged, 80 and over, Predictive marker, biology, GAPDH, Glyceraldehyde-3-Phosphate Dehydrogenases, OxPhos, Middle Aged, glycolysis, Prognosis, 3. Good health, Metformin, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Treatment Outcome, Vincristine, R-CHOP, mTOR, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Lymphoma, Large B-Cell, Diffuse, Rituximab, predictive marker, medicine.drug, Adult, Antimetabolites, Antineoplastic, Mice, Transgenic, Gene Expression Regulation, Enzymologic, 03 medical and health sciences, Young Adult, stomatognathic system, medicine, Animals, Humans, Molecular Biology, Cyclophosphamide, PI3K/AKT/mTOR pathway, B cell, Aged, Retrospective Studies, Glutaminolysis, business.industry, Cell Biology, medicine.disease, L-asparaginase, Mice, Inbred C57BL, 030104 developmental biology, HEK293 Cells, chemistry, Doxorubicin, DLBCL, biology.protein, Cancer research, Prednisone, business, Diffuse large B-cell lymphoma, 030217 neurology & neurosurgery
Abstract

International audience; Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease treated with anti-CD20-based immuno-chemotherapy (R-CHOP). We identified that low levels of GAPDH predict a poor response to R-CHOP treatment. Importantly, we demonstrated that GAPDH(low) lymphomas use OxPhos metabolism and rely on mTORC1 signaling and glutaminolysis. Consistently, disruptors of OxPhos metabolism(phenformin) or glutaminolysis (L-asparaginase) induce cytotoxic responses in GAPDH(low) B cells and improve GAPDH(low) B cell-lymphoma-bearing mice survival, while they are low or not efficient on GAPDH(high) B cell lymphomas. Ultimately, we selected four GAPDH(low) DLBCL patients, who were refractory to all anti-CD20-based therapies, and targeted DLBCL metabolism-using L-asparaginase (K), mTOR inhibitor (T), and metformin (M) (called KTM therapy). Three out of the four patients presented a complete response upon one cycle of KTM. These findings establish that the GAPDH expression level predicts DLBCL patients' response to R-CHOP treatment and their sensitivity to specific metabolic inhibitors.

Published
2019
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13. REFINEMENT OF MUM1 EXPRESSION THRESHOLD FOR DOUBLE POSITIVE CD10+ MUM1+ DIFFUSE LARGE B CELL LYMPHOMA ALLOWS A BETTER CELL OF ORIGIN CLASSIFICATION FOR GCB SUBTYPE

Author

Tony Petrella, W. El Alami Thomas, Danielle Canioni, Hervé Maisonneuve, O. Laghmari, A. Pavageau, P. Gaulard, Y. Le Bris, C. Copie Bergman, Antoine Bonnet, Josette Brière, P. Guerzider, Marie-Christine Béné, O. Casasnovas, Corinne Haioun, Gilles Salles, Thierry Jo Molina, H. Tilly, Anne-Sophie Moreau, Fabrice Jardin, Céline Bossard, Philippe Ruminy, Catherine Thieblemont, and S. Le Gouill

Subjects
Cancer Research, Oncology, Chemistry, Cell of origin, Double negative, medicine, Hematology, General Medicine, medicine.disease, Molecular biology, Diffuse large B-cell lymphoma
Published
2019
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14. Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse

Author

Hélène Sauvageon, Samia Mourah, Eric de Kerviler, Josette Brière, Lauriane Goldwirt, Sandy Amorim, Pauline Brice, Sophie Bernard, and Catherine Thieblemont

Subjects
Male, Oncology, medicine.medical_specialty, Immunology, Central nervous system, Antineoplastic Agents, Lymphoma, Mantle-Cell, Biochemistry, Central Nervous System Neoplasms, chemistry.chemical_compound, Cerebrospinal fluid, Piperidines, Recurrence, Internal medicine, medicine, Humans, Bruton's tyrosine kinase, Aged, Bing–Neel syndrome, biology, business.industry, Adenine, Cell Biology, Hematology, Middle Aged, medicine.disease, Lymphoma, Pyrimidines, medicine.anatomical_structure, chemistry, Ibrutinib, biology.protein, Pyrazoles, Female, Mantle cell lymphoma, business, Antimetabolite Chemotherapy
Abstract

The risk of central nervous system (CNS) dissemination in mantle cell lymphoma (MCL) is low and occurs late in the course of the disease. However, prognosis in such cases remains extremely poor despite high-dose antimetabolite chemotherapy. Among novel drugs used to treat relapsing MCL patients, ibrutinib, an oral inhibitor of Bruton tyrosine kinase, shows great promise. Here we report the clinical observation of 3 MCL patients with symptomatic CNS relapse treated with single-agent ibrutinib. All 3 patients had dramatic and rapid responses with almost immediate recovery from symptoms. We also confirmed that ibrutinib crosses the blood-brain barrier with parallel pharmacokinetic analyses in plasma and cerebrospinal fluid using a validated LC-MS/MS method. All responses were ongoing after 2 months to 1 year of follow-up.

Published
2015
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15. Diagnostic Yield and Safety of Computed Tomography–guided Mediastinal Core Needle Biopsies

Author

Constance de Margerie-Mellon, Jacques Frija, Cédric de Bazelaire, Pauline Brice, Eric de Kerviler, Josette Brière, Abdellatif Tazi, and Sandy Amorim

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, Lymphoproliferative disorders, Radiation Dosage, Radiography, Interventional, Single Center, Asymptomatic, Biopsy, Mediastinal Diseases, medicine, Humans, Radiology, Nuclear Medicine and imaging, Medical diagnosis, Aged, Retrospective Studies, Aged, 80 and over, Lung, medicine.diagnostic_test, business.industry, Mediastinum, Middle Aged, medicine.disease, medicine.anatomical_structure, Female, Biopsy, Large-Core Needle, Patient Safety, Sarcoidosis, Radiology, medicine.symptom, Tomography, X-Ray Computed, Complication, business
Abstract

PURPOSE Mediastinal masses of various origins can be encountered on imaging in symptomatic or asymptomatic patients. We aimed to evaluate the diagnostic yield and complication rate of computed tomography (CT)-guided mediastinal core needle biopsies in a large population of patients presenting with mediastinal masses and to identify the factors that could influence these results. MATERIALS AND METHODS In total, 293 consecutive CT-guided mediastinal biopsies, performed in 285 patients with equivocal masses at a single center from 2006 to 2011, were included. Lesion characteristics, technical biopsy parameters, final diagnoses, diagnostic yields (number of biopsies that yielded a complete diagnosis divided by the total number of biopsies), and complication rates were recorded. RESULTS Malignant diagnoses, including lymphoproliferative disorders (N=151, 53%) and lung cancers (N=54, 19%), were established in 233 cases (82%). Benign lesions were found in 52 procedures (18%), including sarcoidosis (N=19, 7%) and infections (N=17, 6%). The overall diagnostic yield was 87% and was lower for lymphoma residual masses (57%) than for initial diagnosis or relapses of known disease (90%). Complications occurred in 21 patients (7%), but only 2 patients (0.7%) required hospitalization for >12 hours. Neither the diagnostic yield nor the complication rate was influenced by the target characteristics or by technical parameters. CONCLUSIONS CT-guided core needle biopsy of equivocal mediastinal masses is a minimally invasive procedure that is effective and safe, even in cases of small targets or targets in challenging locations.

Published
2015
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17. PET2-driven de-escalation therapy in 64 high-risk Hodgkin Lymphoma patients treated with escalated BEACOPP

Author

Bénédicte Deau, Pauline Brice, Jessica Ohnona, Catherine Thieblemont, Patricia Franchi, Jerome Tamburini, and Josette Brière

Subjects
Oncology, BEACOPP, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, Procarbazine, Bleomycin, Prednisone, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Doxorubicin, Medical physics, Etoposide, Neoplasm Staging, business.industry, Hematology, medicine.disease, Hodgkin Disease, Lymphoma, Treatment Outcome, Vincristine, Positron-Emission Tomography, business, De-escalation, medicine.drug
Published
2015
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18. Long-term outcomes of adults with first-relapsed/refractory systemic anaplastic large-cell lymphoma in the pre-brentuximab vedotin era: A LYSA/SFGM-TC study

Author

Emmanuel Bachy, Anne Sonet, Corinne Haioun, Hervé Tilly, Camille Laurent, Richard Delarue, Laurence Lamant, Philippe Gaulard, Josette Brière, Olivier Tournilhac, Sandy Amorim, David Sibon, Michael Loschi, Alexandre Morel, Université de Nantes (UN), 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'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), 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), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Catholique de Louvain = Catholic University of Louvain (UCL), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), 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), 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 de biologie et modélisation de la cellule (LBMC UMR 5239), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Laboratoire SYstèmes et Matériaux pour la MEcatronique ( SYMME ), Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ), Laboratoire d'Electronique et des Technologies de l'Information ( CEA-LETI ), Université Grenoble Alpes [Saint Martin d'Hères]-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Université Toulouse III - Paul Sabatier ( UPS ), CRLCC Henri Becquerel, Université Paris-Est Créteil Val-de-Marne - Faculté de médecine ( UPEC Médecine ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie Clinique Adulte et de Thérapie Cellulaire, Centre Hospitalier Universitaire de Clermont-Ferrand, Centre International de Recherche en Infectiologie ( CIRI ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Catholique de Louvain ( UCL ), Université Paris Diderot - Paris 7 ( UPD7 ), Laboratoire de Parasitologie-Mycologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Departement de Pathologie, Institut Claudius Regaud,Toulouse, Fédération Nationale des Centres de Lutte contre le Cancer, 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 ), 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 ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Laboratoire d'hématologie ( ERL 8254 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], 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)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Université Catholique de Louvain (UCL), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
Male, Cancer Research, Immunoconjugates, Vindesine, Survival, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Anaplastic lymphoma kinase, Medicine, Relapse, 10. No inequality, Brentuximab vedotin, Anaplastic large-cell lymphoma, ComputingMilieux_MISCELLANEOUS, Cause of death, Aged, 80 and over, Brentuximab Vedotin, ALK protein, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, 3. Good health, Oncology, Vincristine, 030220 oncology & carcinogenesis, Lymphoma, Large-Cell, Anaplastic, Female, medicine.drug, Adult, medicine.medical_specialty, Bleomycin, Young Adult, 03 medical and health sciences, Refractory, Internal medicine, Humans, Cyclophosphamide, Aged, Retrospective Studies, business.industry, medicine.disease, Survival Analysis, Confidence interval, Lymphoma, Clinical trial, Doxorubicin, Prednisone, business, 030215 immunology
Abstract

Background Long-term outcomes of adults with first-relapsed/refractory (R/R) systemic anaplastic large-cell lymphoma (ALCL) are not definitively established and should be evaluated. Patients and methods We previously published the long-term outcomes of adults with ALCL initially treated with polychemotherapy in LYmphoma Study Association (LYSA) prospective clinical trials conducted during the pre-brentuximab vedotin era. Herein, we report the long-term outcomes of those patients after the first-relapsed/refractory (R/R) events. Results Among the 138 (64 (anaplastic lymphoma kinase (ALK(+)) and 74 ALK(−) ALCL) adults initially treated in clinical trials, 40 (14 ALK(+) and 26 ALK(−)) first-R/R ALCL patients and their long-term outcomes were analysed. Median follow-up from the first-R/R events was 12.5 years. For ALK(+) and ALK(−) patients, respectively, median [range] findings were as follows: age at first-R/R event: 35 [19–76] and 61 [34–81] years; time between inclusion in first-line clinical trials and first-R/R events was 6 [1.5–34] and 11.1 [1–67] months (P = 0.36); with median (95% confidence interval) progression-free survival after the first-R/R events: 3.8 (0.7–14.8) and 5.3 (2.4–8.4) months (P = 0.39); and overall survival: 13.6 (0.7–89) and 8.1 (3.3–25) months (P = 0.96). ALCL was the main cause of death. Conclusion Most adults with first-R/R ALCL have poor outcomes, with no significant differences between patients with ALK(+) or ALK(−) disease. These results could be used as reference for the evaluation of new drugs to treat R/R ALCL.

Published
2017
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19. Impact of Expert Pathologic Review of Lymphoma Diagnosis: Study of Patients From the French Lymphopath Network

Author

Mylène Dandoit, Catherine Chassagne-Clément, Alexandra Traverse-Glehen, Gilles Salles, Marie Parrens, Peggy Dartigues, Marie-Pierre Chenard-Neu, Marc Maynadié, B. Fabiani, Pierre Brousset, Françoise Berger, Laurent Martin, Jean-François Michiels, Claire Bastien, Josette Brière, Michel Peoc'h, Patrick Tas, Diane Damotte, Philippe Gaulard, Martine Patey, Nadia Amara, Manuela Delage, Anne Moreau, Isabelle Quintin-Roue, Céline Bossard, Antoine de Mascarel, Marie-Christine Copin, Pierre Déchelotte, Henri Sevestre, Isabelle Soubeyran, Sylvie Thiebault, Luc Xerri, Camille Laurent, Jean-Michel Picquenot, Christiane Copie-Bergman, Antoine Martin, Frédéric Charlotte, Blandine Fabre, Béatrice Vergier, Georges Delsol, Flavie Arbion, Corinne Haioun, Tony Petrella, Marine Baron, Marie-Christine Rousselet, Thomas Filleron, Cécile Le Naoures, Thérèse Rousset, Nicole Brousse, and Thierry Jo Molina

Subjects
Cancer Research, Pathology, medicine.medical_specialty, Myeloid, Lymphoma, Newly diagnosed, 03 medical and health sciences, 0302 clinical medicine, hemic and lymphatic diseases, Medicine, Humans, Lymphoid neoplasms, Prospective Studies, Prospective cohort study, Referral and Consultation, Neoplasm Grading, Potential impact, Pathology, Clinical, business.industry, Lymphoma diagnosis, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Clinical Competence, France, business, Who classification, 030215 immunology
Abstract

Purpose To prospectively assess the clinical impact of expert review of lymphoma diagnosis in France. Materials and Methods From January 2010 to December 2013, 42,145 samples from patients with newly diagnosed or suspected lymphomas were reviewed, according to the 2008 WHO classification, in real time by experts through the Lymphopath Network. Changes in diagnosis between referral and expert review were classified as major or minor according to their potential impact on patient care. Results The 42,145 reviewed samples comprised 36,920 newly diagnosed mature lymphomas, 321 precursor lymphoid neoplasms, 314 myeloid disorders, and 200 nonhematopoietic neoplasms, with 4,390 benign lesions. There were 4,352 cutaneous and 32,568 noncutaneous lymphomas. The most common mature noncutaneous lymphomas were diffuse large B-cell lymphomas (32.4%), follicular lymphomas (15.3%), classic Hodgkin lymphomas (13%), peripheral T-cell lymphomas (6.3%) of which angioimmunoblastic T-cell lymphomas (2.3%) were the most frequent, and mucosa-associated lymphoid tissue lymphomas (5.8%). A diagnostic change between referral and expert review occurred in 19.7% of patients, with an estimated impact on patient care for 17.4% of patients. This rate was significantly higher for patients sent with a provisional diagnosis seeking expert second opinion (37.8%) than for patients sent with a formal diagnosis (3.7%). The most frequent discrepancies were misclassifications in lymphoma subtype (41.3%), with 12.3% being misclassifications among small B-cell lymphoma entities. Fewer than 2% of changes were between benign and malignant lymphoid conditions. Minor changes (2.3%) mostly consisted of follicular lymphoma misgrading and diffuse large B-cell lymphoma subtype misclassification. Conclusion To our knowledge, this study provides the largest ever description of the distribution of lymphoma entities in a western country and highlights how expert review significantly contributes to a precise lymphoma diagnosis and optimal clinical management in a proportion of patients.

Published
2017

20. BCL2 expression but not MYC and BCL2 coexpression predicts survival in elderly patients with diffuse large B-cell lymphoma independently of cell of origin in the phase 3 LNH03-6B trial

Author

Gilles Salles, Martin Figeac, Hervé Tilly, B. Fabiani, Josette Brière, Danielle Canioni, M. Parrens, Marc André, R. Delarue, Jean-Philippe Jais, C Thieblemont, Christiane Copie-Bergman, Karen Leroy, Corinne Haioun, P. Feugier, Philippe Ruminy, Fabrice Jardin, Tony Petrella, Thierry Jo Molina, P. Gaulard, 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, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre d'études spatiales de la biosphère (CESBIO), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), 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 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'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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 Necker - Enfants Malades [AP-HP], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CHU Bordeaux [Bordeaux]

Subjects
0301 basic medicine, Oncology, Male, Pathology, [SDV]Life Sciences [q-bio], Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, International Prognostic Index, Risk Factors, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Hazard ratio, Hematology, Middle Aged, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, Treatment Outcome, Proto-Oncogene Proteins c-bcl-2, Vincristine, 030220 oncology & carcinogenesis, Prednisolone, Rituximab, Female, Lymphoma, Large B-Cell, Diffuse, medicine.drug, medicine.medical_specialty, Disease-Free Survival, Proto-Oncogene Proteins c-myc, 03 medical and health sciences, Internal medicine, medicine, Biomarkers, Tumor, Humans, Progression-free survival, Cyclophosphamide, Aged, business.industry, medicine.disease, Lymphoma, 030104 developmental biology, Doxorubicin, Prednisone, business, Diffuse large B-cell lymphoma
Abstract

Background Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial. Patients and methods We evaluated 285 paraffin-embedded samples from patients (60–80years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples. Results The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81). Conclusions Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival. Clinical trial Number NCT00144755

Published
2017
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21. GAPDH enhances the aggressiveness and the vascularization of non-Hodgkin’s B lymphomas via NF-κB-dependent induction of HIF-1α

Author

Josette Brière, Diogo Gonçalvès, M Guyot, Nicolas Mounier, A Mouchotte, Marie Bénéteau, Véronique Imbert, Catherine Thieblemont, Ophélie Meynet, Johanna Chiche, Sandrine Marchetti, Laura Mondragón, S Pommier, Michel Carles, J-E Ricci, Pascal Colosetti, Barbara Zunino, E Verhoeyen, and Gilles Pagès

Subjects
Vascular Endothelial Growth Factor A, Cancer Research, TRAF2, Lymphoma, Biopsy, Mice, Transgenic, Gene Expression Regulation, Enzymologic, Proto-Oncogene Proteins c-myc, Mice, chemistry.chemical_compound, stomatognathic system, Cell Line, Tumor, medicine, Animals, Humans, Enzyme Inhibitors, Glyceraldehyde 3-phosphate dehydrogenase, Regulation of gene expression, biology, Lymphoma, Non-Hodgkin, NF-kappa B p50 Subunit, NF-κB, Hematology, Hypoxia-Inducible Factor 1, alpha Subunit, TNF Receptor-Associated Factor 2, medicine.disease, Molecular biology, Gene Expression Regulation, Neoplastic, Phenotype, Oncology, chemistry, Cell culture, Tumor progression, biology.protein, Tumor necrosis factor alpha, Glyceraldehyde 3-Phosphate Dehydrogenase (NADP+), HeLa Cells
Abstract

Deregulated expression of glycolytic enzymes contributes not only to the increased energy demands of transformed cells but also has non-glycolytic roles in tumors. However, the contribution of these non-glycolytic functions in tumor progression remains poorly defined. Here, we show that elevated expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), but not of other glycolytic enzymes tested, increased aggressiveness and vascularization of non-Hodgkin's lymphoma. Elevated GAPDH expression was found to promote nuclear factor-κB (NF-κB) activation via binding to tumor necrosis factor receptor-associated factor-2 (TRAF2), enhancing the transcription and the activity of hypoxia-inducing factor-1α (HIF-1α). Consistent with this, inactive mutants of GAPDH failed to bind TRAF2, enhance HIF-1 activity or promote lymphomagenesis. Furthermore, elevated expression of gapdh mRNA in biopsies from diffuse large B-cell non-Hodgkin's lymphoma patients correlated with high levels of hif-1α, vegf-a, nfkbia mRNA and CD31 staining. Collectively, these data indicate that deregulated GAPDH expression promotes NF-κB-dependent induction of HIF-1α and has a key role in lymphoma vascularization and aggressiveness.

Published
2014
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22. Lymphoma and Epstein−Barr virus DNA in blood during interleukin-2 therapy in antiretroviral-naïve HIV-1-infected patients: a substudy of the ANRS 119 trial

Author

Thomas Boulet, J. P. Aboulker, Jean-Michel Molina, Josette Brière, François Simon, Félix Agbalika, Jérôme LeGoff, V. de Lastours, and Yves Levy

Subjects
medicine.medical_specialty, biology, business.industry, Health Policy, medicine.disease, medicine.disease_cause, biology.organism_classification, Epstein–Barr virus, Gastroenterology, Virus, Lymphoma, law.invention, Non-Hodgkin's lymphoma, Infectious Diseases, law, hemic and lymphatic diseases, Internal medicine, Blood plasma, Immunology, medicine, Pharmacology (medical), business, Sida, Burkitt's lymphoma, Polymerase chain reaction
Abstract

Objectives Interleukin-2 (IL-2) therapy increased CD4 cell counts and delayed antiretroviral therapy (ART) initiation in HIV-infected patients in the Agence Nationale de Recherche sur le SIDA et les Hepatites Virales (ANRS) 119 trial. However, four cases of lymphoma were reported. Epstein−Barr virus (EBV) replication is associated with an increased risk of lymphoma in immunocompromised patients. We assessed whether IL-2 had an impact on EBV replication and the development of lymphoma. Methods A total of 130 ART-naive patients were randomized to receive IL-2 therapy (n = 66) or no treatment (n = 64). Clinical data for patients with lymphomas were reviewed and tumours assessed for evidence of EBV infection and CD25 (the IL-2 receptor) expression. EBV DNA levels were measured in whole blood and plasma in both arms using real-time polymerase chain reaction (PCR), up to 48 weeks after baseline (BL). Results Four lymphomas occurred, a median of 61 weeks [range 40−94 weeks] after randomization at a median CD4 cell count of 396 cells/μL (IQR 234–536 cells/μL). In the IL-2 arm, two patients developed EBV-positive Hodgkin's lymphoma, and one developed EBV-negative Burkitt-type lymphoma. One patient in the control group developed EBV-positive non-Hodgkin's lymphoma. CD25 was negative in all cases. Among the 41 of 55 (control arm) and 44 of 58 (IL-2 arm) patients with detectable EBV DNA in whole blood at both BL and week 48, the median change in EBV DNA between BL and week 48 was +0.04 log10 copies/ml in both arms (P = 0.7). In plasma, EBV was detected at least once in 22 of 52 controls and 21 of 54 IL-2-treated patients (P = 0.8). Conclusions IL-2 therapy had no significant effect on EBV replication over 48 weeks in these ART-naive patients. The occurrence of lymphomas did not seem to be associated with IL-2 therapy.

Published
2013
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23. Specific lymph node involvement in scleromyxedema: a new diagnostic entity for hypermetabolic lymphadenopathy

Author

Martine Bagot, Josette Brière, Maud Bézier, Julie Delyon, Pierre Validire, Anne Janin, Michel Rybojad, and Maxime Battistella

Subjects
Male, Pathology, medicine.medical_specialty, Paraproteinemias, Lymph node biopsy, Pathology and Forensic Medicine, Immunoglobulin kappa-Chains, Scleromyxedema, medicine, Humans, Glucocorticoids, Lymphatic Diseases, Molecular Biology, Lymph node, Aged, Skin, PET-CT, medicine.diagnostic_test, business.industry, Mediastinum, Immunoglobulins, Intravenous, Cell Biology, General Medicine, Fibroblasts, medicine.disease, Mucinosis, Treatment Outcome, medicine.anatomical_structure, Positron emission tomography, Immunoglobulin G, Skin biopsy, Lymph Nodes, Lymph, business
Abstract

Scleromyxedema is a generalized skin disease mostly associated with monoclonal gammopathy. In its chronic course, it can lead to systemic disorders related to mucin deposits in organs. We describe here specific lymph node involvement, hitherto not reported in scleromyxedema. A 68-year-old man with a 1-year history of micropapular eruption and skin sclerosis involving the neck, trunk, hands, and face was diagnosed with scleromyxedema associated with IgG kappa monoclonal gammopathy. Enlarged mediastinal lymph nodes found on thoracic X-ray and computed tomography scan were hypermetabolic on positron emission tomography. Lymph node biopsy showed partial nodal infiltration by numerous fibroblasts surrounded by mucin and collagen deposits, the same being observed on the skin biopsy. Lymph node and skin lesions both improved after intravenous immunoglobulin and corticosteroid treatment. Lymph node involvement in scleromyxedema should be considered in the etiological diagnosis of hypermetabolic, enlarged lymph nodes, especially if monoclonal gammopathy is associated.

Published
2013
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25. At diagnosis, diffuse large B-cell lymphoma patients show impaired rituximab-mediated NK-cell cytotoxicity

Author

Catherine Thieblemont, Nicolas Dulphy, Antoine Toubert, Guylaine Henry, Daniela Geromin, Zena Khaznadar, Josette Brière, Anne Danielou-Lazareth, Ryad Tamouza, and Jean-Michel Cayuela

Subjects
Antibody-dependent cell-mediated cytotoxicity, Immunology, CD137, CD16, Biology, medicine.disease, Lymphoma, Immunophenotyping, immune system diseases, hemic and lymphatic diseases, Monoclonal, medicine, Immunology and Allergy, Rituximab, Diffuse large B-cell lymphoma, medicine.drug
Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma in adults. It is generally treated by a combination of chemotherapy and CD20-specific mAbs, such as rituximab, which act, at least partially, by activating antibody-dependent cell-mediated cytotoxicity (ADCC). ADCC involves NK cells, particularly the CD56(dim) NK-cell subset expressing CD16, the low affinity Fcγ receptor. Here, we show that CD16 expression levels are decreased in a cohort of 36 newly diagnosed DLBCL patients compared with those in 20 healthy controls (HCs). CD137, a co-stimulatory molecule expressed on activated NK cells, was also expressed at lower levels in patients compared with controls. Cells sampled from our cohort also showed severely reduced degranulation activity when challenged with rituximab-coated tumor cells, which could not be corrected by stimulation with high doses of IL-2. These results suggest that rituximab-induced NK-cell ADCC could be defective in some DLBCL patients at diagnosis. These patients should be closely monitored and attempts made to improve their NK-cell function.

Published
2013
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26. ABVD or BEACOPP

Author

Christophe, Fermé, José, Thomas, Pauline, Brice, Olivier, Casasnovas, Andrej, Vranovsky, Serge, Bologna, Pieternella J, Lugtenburg, Réda, Bouabdallah, Patrice, Carde, Catherine, Sebban, Houchingue, Eghbali, Gilles, Salles, Gustaaf W, van Imhoff, Antoine, Thyss, Evert M, Noordijk, Oumédaly, Reman, Marnix L M, Lybeert, Maud, Janvier, Michele, Spina, Bruno, Audhuy, John M M, Raemaekers, Richard, Delarue, Bruno, Anglaret, Okke, de Weerdt, Zora, Marjanovic, Robbert J H A, Tersteeg, Daphne, de Jong, Josette, Brière, and Michel, Henry-Amar

Subjects
Adult, Male, Adolescent, Radiotherapy, Middle Aged, Vinblastine, Combined Modality Therapy, Hodgkin Disease, Survival Analysis, Dacarbazine, Bleomycin, Young Adult, Doxorubicin, Risk Factors, Vincristine, Procarbazine, Antineoplastic Combined Chemotherapy Protocols, Humans, Prednisone, Female, Cyclophosphamide, Aged, Etoposide
Abstract

For early-stage Hodgkin lymphoma (HL), optimal chemotherapy regimen and the number of cycles to be delivered remain to settle down. The H9-U trial compared three modalities of chemotherapy followed by involved-field radiotherapy (IFRT) in patients with stage I-II HL and risk factors (NCT00005584).Patients aged 15-70 years with untreated supradiaphragmatic HL with at least one risk factor (age ≥ 50, involvement of 4-5 nodal areas, mediastinum/thoracic ratio ≥ 0.35, erythrocyte sedimentation rate (ESR) ≥ 50 without B-symptoms or ESR ≥ 30 and B-symptoms) were eligible for the randomised, open label, multicentre, non-inferiority H9-U trial. The limit of non-inferiority was set at 10% for the difference between 5-year event-free survival (EFS) estimates. From October 1998 to September 2002, 808 patients were randomised to receive either the control arm 6-ABVD-IFRT (n = 276), or one of the two experimental arms: 4-ABVD-IFRT (n = 277) or 4-BEACOPPResults in the 4-ABVD-IFRT (5-year EFS, 85.9%) and the 4-BEACOPPThe trial demonstrates that 4-ABVD followed by IFRT yields high disease control in patients with early-stage HL and risk factors responding to chemotherapy. Although non-inferior in terms of efficacy, four cycles of BEACOPP

Published
2017

27. ER stress in diffuse large B cell lymphoma: GRP94 is a possible biomarker in germinal center versus activated B-cell type

Author

Heleen Van Melckebeke, Karen Leroy, Barbara Vanhoecke, Jean-Philippe Jais, Sofie Lust, Fabrice Jardin, Josette Brière, Jerina Boelens, Fritz Offner, Jan Philippé, Marc Bracke, and Ilse M. Beck

Subjects
Cancer Research, Pathology, medicine.medical_specialty, Cell, Apoptosis, Cell Line, Tumor, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, medicine, Humans, Cyclophosphamide, B cell, Membrane Glycoproteins, business.industry, Germinal center, Hematology, Endoplasmic Reticulum Stress, medicine.disease, Lymphoma, medicine.anatomical_structure, Oncology, Doxorubicin, Vincristine, Cell culture, Unfolded Protein Response, Unfolded protein response, Cancer research, Prednisone, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma
Abstract

The process of B-cell development is characterized by the activation of the unfolded protein response. Under certain circumstances, the unfolded protein response can be manipulated in a cell death-inducing way. Therefore, tackling the unfolded protein response might be an attractive strategy in the treatment of diffuse large B-cell lymphomas. Our research showed more basal unfolded protein response activity and differences in the inducibility of ER stress in activated B-cell versus germinal center cell lines. Moreover, the diffuse large B cell lymphoma patient data revealed that the glucose-regulated protein 94 is new potential discriminator for diffuse large B cell lymphoma.

Published
2013
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28. Outcomes of diffuse large B-cell lymphoma patients relapsing after autologous stem cell transplantation: an analysis of patients included in the CORAL study

Author

M. Bargetzi, R Bouadballah, B. Glass, Christian Gisselbrecht, Devinder Gill, Josette Brière, Nicolas Mounier, David D.F. Ma, C Thieblemont, John Radford, Emmanuel Bachy, Norbert Schmitz, Ulrich Dührsen, Dc Linch, Craig H. Moskowitz, Vincent Ribrag, E. Van Den Neste, and Marek Trneny

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Allogeneic transplantation, Adolescent, medicine.medical_treatment, Medizin, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Recurrence, Internal medicine, medicine, Humans, Autografts, Survival rate, Aged, Transplantation, Chemotherapy, business.industry, Hematology, Middle Aged, medicine.disease, Lymphoma, Surgery, Survival Rate, Graft-versus-host disease, 030220 oncology & carcinogenesis, Female, Lymphoma, Large B-Cell, Diffuse, business, Diffuse large B-cell lymphoma, 030215 immunology, Stem Cell Transplantation
Abstract

In the CORAL study, 255 chemosensitive relapses with diffuse large B-cell lymphoma (DLBCL) were consolidated with autologous stem cell transplantation (ASCT), and 75 of them relapsed thereafter. The median time between ASCT and progression was 7.1 months. The median age was 56.1 years; tertiary International Prognosis Index (tIPI) observed at relapse was 0-2 in 71.6% of the patients and2 in 28.4%. The overall response rate to third-line chemotherapy was 44%. The median overall survival (OS) was 10.0 months (median follow-up: 32.8 months). Thirteen patients received an allogeneic SCT, and three a second ASCT. The median OS was shorter among patients who relapsed6 months (5.7 months) compared with those relapsing ⩾12 months after ASCT (12.6 months, P=0.0221). The median OS in patients achieving CR, PR or no response after the third-line regimen was 37.7 (P0.0001), 10.0 (P=0.03) and 6.3 months, respectively. The median OS varied according to tIPI: 0-2: 12.6 months and2: 5.3 months (P=0.0007). In multivariate analysis, tIPI2, achievement of response and remission lasting6 months predicted the OS. This report identifies the prognostic factors for DLBCL relapsing after ASCT and thus helps to select patients for experimental therapy.

Published
2016

29. Brentuximab vedotin in refractory or relapsed peripheral T-cell lymphomas: the French named patient program experience in 56 patients

Author

Richard Delarue, Céline Bossard, Emmanuel Bachy, Corinne Haioun, Mathilde Lamarque, Adrien Contejean, Josette Brière, Hervé Tilly, Steven Le Gouill, Marie Parrens, Philippe Gaulard, Pauline Brice, Reda Bouabdallah, Brigitte Bouchindhomme, Danielle Canioni, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire d'anatomie et cytologie pathologiques, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Hematologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Necker - Enfants Malades [AP-HP], Département d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Service de pathologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], UMR INSERM U955, École nationale vétérinaire - Alfort (ENVA), Service d'hématologie clinique, Département de pathologie [Mondor], Bernardo, Elizabeth, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), 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 universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Centre d’Investigation Clinique de Nantes ( CIC Nantes ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Ecole Nationale Vétérinaire d'Alfort, and École nationale vétérinaire d'Alfort (ENVA)

Subjects
Oncology, medicine.medical_specialty, CD30, T cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigen, Refractory, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Brentuximab vedotin, Online Only Articles, ComputingMilieux_MISCELLANEOUS, business.industry, Hematology, medicine.disease, Primary cutaneous T-cell lymphoma, 3. Good health, Peripheral, Lymphoma, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, business, 030215 immunology, medicine.drug
Abstract

Brentuximab vedotin (BV) is an antibody-drug-conjugate directed against CD30 antigen, recently approved for the treatment of relapsed anaplastic large-cell lymphomas (ALCL).[1][1] It has further been suggested that a significant proportion of peripheral T-cell lymphomas (PTCL) may be potential

Published
2016
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30. Therapy-related classical Hodgkin lymphoma after a primary haematological malignancy: a report on 13 cases

Author

Catherine Thieblemont, Marie-Dominique Venon, Jean-Michel Miclea, Lionel Galicier, Pauline Brice, Marie Robin, Josette Brière, David Boutboul, and Morgane Cheminant

Subjects
Adult, Male, Oncology, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, macromolecular substances, Monoclonal antibody, Immunophenotyping, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, polycyclic compounds, Classical Hodgkin lymphoma, medicine, Humans, Disseminated disease, In patient, Aged, Chemotherapy, Therapy related, business.industry, food and beverages, Hematology, Middle Aged, medicine.disease, Hodgkin Disease, Treatment Outcome, Hematologic Neoplasms, Hodgkin lymphoma, Female, Neoplasm Recurrence, Local, business, Haematological malignancy
Abstract

Summary The risk of developing Hodgkin lymphoma (HL) is increased in immunodeficiencies or during the treatment of some autoimmune diseases. The development of new therapeutic agents has highlighted the risk of unusual lymphoid proliferations, particularly classical HL (cHL). We report the clinicopathological findings of 13 cHL arising in patients treated for a primary haematological malignancy. Eight patients had received an immunomodulator, protein tyrosine-kinase inhibitor or monoclonal antibody, which may have contributed to the cHL development. Most patients had disseminated disease with poor prognostic factors at cHL diagnosis. Despite the initial presentation, good outcomes were achieved with standard cHL chemotherapy.

Published
2012
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31. BCL2 expression in CD105 positive neoangiogenic cells and tumor progression in angioimmunoblastic T-cell lymphoma

Author

Wei-Li Zhao, Philippe Ratajczak, Christophe Leboeuf, Irmine Loisel-Ferreira, Anne Janin, Josette Brière, Catherine Thieblemont, Li Wang, Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Pathogenesis of Leukemia, Shanghai Jiao Tong University School of Medicine-Shanghai Rui Jin Hospital-Shanghai Institute for Biological Sciences Chinese Academy of Sciences, Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie-oncologie adultes, and Ratajczak, Philippe

Subjects
Male, Vascular Endothelial Growth Factor A, Pathology, Time Factors, Angiogenesis, CD34, Fluorescent Antibody Technique, Antigens, CD34, Kaplan-Meier Estimate, 0302 clinical medicine, Risk Factors, immune system diseases, hemic and lymphatic diseases, Tumor Microenvironment, Aged, 80 and over, 0303 health sciences, Neovascularization, Pathologic, Endoglin, Middle Aged, VEGF, CD105, Vascular endothelial growth factor A, Treatment Outcome, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, 030220 oncology & carcinogenesis, Disease Progression, endothelial cell, Female, Adult, Paris, BCL2, neoangiogenesis, Angioimmunoblastic T-cell lymphoma, medicine.medical_specialty, Receptors, Cell Surface, [SDV.CAN]Life Sciences [q-bio]/Cancer, Laser Capture Microdissection, Angioimmunolbastic T-Cell Lyphoma, Biology, Lymphoma, T-Cell, Real-Time Polymerase Chain Reaction, Risk Assessment, Disease-Free Survival, Article, Pathology and Forensic Medicine, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigens, CD, Biomarkers, Tumor, medicine, Humans, RNA, Messenger, Aged, Proportional Hazards Models, 030304 developmental biology, Tumor microenvironment, Chi-Square Distribution, Endothelial Cells, medicine.disease, Lymphoma, Tumor progression, Case-Control Studies, Immunoblastic Lymphadenopathy, Microvessels, Multivariate Analysis, Lymph Nodes, Bone marrow
Abstract

International audience; The angiogenic microenvironment has been known to be a component of angioimmunoblastic T-cell lymphoma since its initial characterization. We have shown that angioimmunoblastic T-cell lymphoma endothelial cells produce vascular endothelial growth factor-A (VEGFA), and participate in lymphoma progression. In squamous cell carcinoma, endothelial BCL2 expression induces a crosstalk with tumor cells through VEGFA, a major mediator of tumoral angiogenesis. In the present study, we analyzed BCL2 and VEGFA in 30 angioimmunoblastic T-cell lymphomas, using triple immunofluorescence to identify protein coexpression in well-characterized lymphoma cells and microenvironment neoangiogenic endothelial cells. Using quantitative real-time PCR, we assessed mRNA expression levels in laser-microdissected endothelial and lymphoma cells. In lymphoma cells, as in endothelial cells, BCL2 and VEGFA proteins were coexpressed. BCL2 was expressed only in neoangiogenic CD34(+)CD105(+) endothelial cells. In laser-microdissected cells, mRNA studies showed a significant relationship between BCL2 and VEGFA levels in CD34(+) endothelial cells, but not in CD3(+)CD10(+)lymphoma cells, or in CD34(+) endothelial cells from lymph node hyperplasia. Further study showed that, in AITL, BCL2 mRNA levels in CD34(+)CD105(+) neoangiogenic endothelial cells also correlated with microvessel density, International Prognostic Index, Ann Arbor stage, bone marrow involvement and elevated LDH. BCL2 expression by CD105(+) neoangiogenic endothelial cells is related to tumor progression in angioimmunoblastic T-cell lymphoma.

Published
2012
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32. Image-guided needle biopsy for diagnosis and molecular biology in lymphomas

Author

C. Benet, E. de Kerviler, C. de Bazelaire, and Josette Brière

Subjects
Core needle, medicine.medical_specialty, Pathology, Lymphoma, Clinical Biochemistry, Lymph node biopsy, Diagnostic evaluation, Specimen Handling, Recurrence, Image Interpretation, Computer-Assisted, Biopsy, Biomarkers, Tumor, medicine, Humans, Tomography, In Situ Hybridization, Fluorescence, Ultrasonography, medicine.diagnostic_test, business.industry, Biopsy, Needle, medicine.disease, Diagnostic strategy, Immunohistochemistry, Molecular analysis, Oncology, Needle biopsy, Disease Progression, Lymph Nodes, Radiology, business
Abstract

Core needle biopsy is increasingly replacing excisional lymph node biopsy in the diagnosis and subclassification of malignant lymphomas, with obvious advantages in terms of morbidity and costs. This technique has radically altered the diagnostic strategy of enlarged lymph nodes at our institution, avoiding unnecessary nodal excisions. It represents a viable alternative as long as the number and size of cores for morphologic and molecular studies are not compromised. This quick and safe technique can be applied to the initial diagnostic evaluation of malignant lymphomas as well as the reassessment of previously diagnosed malignant lymphomas at time of progression or recurrence.

Published
2012
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33. Intérêt de la biopsie ostéomédullaire dans la thrombocytémie essentielle

Author

Josette Brière, Jean-François Viallard, Noel Milpied, Olivier Rager, Jean-Luc Pellegrin, Eric Lippert, and Marie Parrens

Subjects
education.field_of_study, Pathology, medicine.medical_specialty, Janus kinase 2, biology, medicine.diagnostic_test, business.industry, Population, General Medicine, medicine.disease, Gastroenterology, Polycythemia vera, medicine.anatomical_structure, Internal medicine, Biopsy, medicine, biology.protein, Bone marrow, Medical diagnosis, business, education, Myelofibrosis, Pathological
Abstract

Summary Introduction The recent discovery of the Janus Kinase 2 (JAK2V617F) mutation, an indicator of clonal expansion, has widely modified the diagnostic work-up of myeloproliferative disorders. However, histopathologic criteria of the WHO classification, focused on megakaryocytes abnormalities, have taken a central role in the diagnosis of essential thrombocytemia (ET), particularly to distinguish it from the prefibrotic myelofibrosis (PMF) evolving to a clinic myelofibrosis unlike true ET. The aim of our study is to evaluate inter-observer reproducibility and prognostic implications of these pathological criteria comparing diagnoses with clinical and biological follow-up. Methods Forty-four patients presenting with isolated thrombocytemia were retrospectively evaluated. All patients were initially diagnosed with ET based on the PVSG classification from 1997. The initial bone marrow biopsy specimens were re-evaluated using the Thiele pathological classification: true ET, prefibrotic myelofibrosis (PMF) and early myelofibrosis. Patients were followed for a median of 6 years. Results Our population includes three patients with polycythemia vera and 41 patients with true ET. Based on clinical and biological follow-up, diagnoses were changed to idiopathic myelofibrosis in four of six patients with “early” myelofibrosis (66.7%), but in only one of 14 patients with PMF (7.15%). In contrast, the diagnosis of true ET was not changed in the 21 cases. Inter-observer reproducibility for pathological classification was 100%. Conclusion In this study, our diagnostic methodology based on the clinico-biological follow-up, which has not been evaluated in previous studies, calls into question the diagnostic value of the pathological criteria in PMF.

Published
2011
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34. Guided needle biopsy: contribution to diagnosis and to laboratory testing

Author

A. Scemama, E. de Kerviler, C. de Bazelaire, Josette Brière, and C. Benet

Subjects
Oncology
Abstract

Les techniques de biopsies guidees par imagerie constituent une alternative raisonnable a l’exerese chirurgicale ganglionnaire dans le diagnostic d’une hemopathie lymphoide, a condition de realiser de multiples prelevements de grande taille, dont certains seront congeles pour des etudes moleculaires eventuelles.

Published
2011
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35. 90Y Ibritumomab Tiuxetan (Zevalin) Combined With BEAM (Z -BEAM) Conditioning Regimen Plus Autologous Stem Cell Transplantation in Relapsed or Refractory Low-grade CD20-positive B-cell Lymphoma. A GELA Phase II Prospective Study

Author

Didier Decaudin, Anne Huynh, Nicolas Mounier, André Bosly, Richard Delarue, Steven Le Gouill, Serge Bologna, Hervé Tilly, Vincent Ribrag, Franck Morschhauser, Bertrand Coiffier, Josette Brière, Christian Gisselbrecht, Hervé Ghesquières, and Krimo Bouabdallah

Subjects
Adult, Melphalan, Oncology, Cancer Research, medicine.medical_specialty, Lymphoma, B-Cell, Adolescent, Follicular lymphoma, Ibritumomab tiuxetan, Antineoplastic Agents, Transplantation, Autologous, Antibodies, Monoclonal, Murine-Derived, Young Adult, Autologous stem-cell transplantation, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Etoposide, Aged, Neoplasm Staging, Podophyllotoxin, CD20, biology, business.industry, Cytarabine, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, medicine.disease, Carmustine, Survival Analysis, Transplantation, Regimen, Treatment Outcome, surgical procedures, operative, Immunology, biology.protein, Rituximab, business, medicine.drug
Abstract

This study was designed to evaluate the safety and efficacy of a conventional dose of yttrium-90 ((90)Y) ibritumomab tiuxetan combined with the etoposide rabinoside acytarabine melphalan (BEAM) regimen before autologous stem cell transplantation (ASCT) in chemosensitive relapsed or refractory low-grade B-cell lymphomas.From March 2005 to August 2006, 77 prospective patients were included, 69 (90%) with follicular lymphomas.The last salvage chemotherapy regimen included rituximab for 74 patients and ASCT for 75 patients. Before ASCT, rates of complete response/unconfirmed response (CR/CRu) and partial response were 77% and 23%, respectively. After zevaline-BEAM (Z-BEAM), time to1 × 10(9)/L neutrophils was 12 days (range, 9-35 days), and time to20 × 10(9)/L platelets was 12 days (range, 3-42 days). No other significant extrahematologic toxicity was observed. Three months after ASCT, 68 patients (88%) were in CR/CRu. After a median follow-up of 28 months, 2-year event-free survival (EFS) and overall survival were 63% and 97%, respectively, but EFS for first-relapsed patients was 72%. When using patients as their own controls, 2-year EFS was superior after ASCT and compared favorably with the duration of response of last chemotherapy (62% vs. 37%, P = .007) (Point 1.10).Z-BEAM appears safe and needs to be further evaluated in a randomized trial.

Published
2011
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36. Combined ifosfamide, etoposide and oxalipatin chemotherapy, a low-toxicity regimen for first-relapsed or refractory Hodgkin lymphoma after ABVD/EBVP: a prospective monocentre study on 34 patients

Author

Catherine Thieblemont, Marjane Ertault, Patricia Franchi, Cédric de Bazelaire, Eric de Kerviler, Josette Brière, Nathalie Beranger, Chadi Al Nawakil, Pauline Brice, and David Sibon

Subjects
medicine.medical_specialty, Chemotherapy, Ifosfamide, business.industry, medicine.medical_treatment, Hematology, medicine.disease, Surgery, Transplantation, Regimen, ABVD, medicine, Refractory Hodgkin Lymphoma, business, Etoposide, Febrile neutropenia, medicine.drug
Abstract

Summary Around 20% of Hodgkin lymphoma (HL) patients are refractory to first-line therapy with ABVD (adriamycin–bleomycin–vinblastine–dacarbazine) or relapse after complete remission. Salvage regimens frequently have delayed courses or require dose-reduction because of haemotoxicity. We evaluated the IVOx (ifosfamide–etoposide–oxaliplatin) salvage regimen in terms of response rate, toxicity and stem-cell mobilization. Thirty-four patients with relapsed/refractory HL after anthracycline-containing chemotherapy prospectively received IVOx, consisting of ifosfamide (1500 mg/m2 days 1–3), etoposide (150 mg/m2 days 1–3) and oxaliplatin (130 mg/m2 day 1). Patients

Published
2011
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37. Aflibercept-mediated early angiogenic changes in aggressive B-cell lymphoma

Author

Li Wang, Cédric de Bazelaire, Martha Romero, Anne Janin, Philippe Ratajczak, Josette Brière, Christophe Lebœuf, Eric de Kerviler, Catherine Thieblemont, and David Sibon

Subjects
Adult, Male, Cancer Research, Pathology, medicine.medical_specialty, Lymphoma, B-Cell, Necrosis, Recombinant Fusion Proteins, Toxicology, Neovascularization, chemistry.chemical_compound, immune system diseases, hemic and lymphatic diseases, Biopsy, medicine, Humans, Pharmacology (medical), B-cell lymphoma, Microvessel, Aged, Ultrasonography, Aflibercept, Aged, 80 and over, Pharmacology, Neovascularization, Pathologic, medicine.diagnostic_test, business.industry, Biopsy, Needle, Middle Aged, medicine.disease, Lymphoma, Vascular endothelial growth factor, Receptors, Vascular Endothelial Growth Factor, Oncology, chemistry, Lymphatic Metastasis, Female, medicine.symptom, business, medicine.drug
Abstract

Diffuse large B-cell lymphoma is the most common and one of the most aggressive lymphomas in adults. The standard, R-CHOP-based treatment needs improvement. There has been recent interest in anti-angiogenic therapy, but its cellular effects in lymphoma are little known. In five aggressive B-cell lymphoma patients, we analyzed the microvessel and lymphoma cell changes after Aflibercept, an angiogenic inhibitor. Under ultrasonography, we performed two biopsies, one before any treatment and one two hours after Aflibercept, before R-CHOP. Using ultrasonography, immuno-histochemistry, double immuno-fluorescent staining, and electron microscopy, we compared the early changes induced by Aflibercept to the early changes induced by R-CHOP in three control patients. We identified microvessel damage in the five patients treated with Aflibercept but not in the three patients treated with R-CHOP. Two hours after Aflibercept, microvessel damage was focal, with severely damaged microvessel sections close to normal ones in the same area; different stages of microvessel damage were concomitantly found, with an increase in relative necrosis area in three cases. There was no difference in necrosis or relative microvessel area after R-CHOP. For lymphoma cells, the two biotherapies induced similar changes, with increase in apoptosis but not in proliferation. We identified focal microvascular damage, necrosis, and apoptosis of lymphoma cells in aggressive B-cell lymphoma as soon as 2 h after Aflibercept. This suggests that there is more than one mechanism associated with the early effect of anti-angiogenic therapy in lymphoma.

Published
2011
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38. Rituximab, Dexamethasone, Cytarabine, and Oxaliplatin (R-DHAX) Is an Effective and Safe Salvage Regimen in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Author

Patricia Franchi, Pierre Faure, Catherine Thieblemont, David Sibon, Julie Lignon, Nicolas Mounier, Christian Gisselbrecht, Pauline Brice, Isabelle Madelaine, and Josette Brière

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Vincristine, Lymphoma, B-Cell, Drug-Related Side Effects and Adverse Reactions, Organoplatinum Compounds, Follicular lymphoma, Salvage therapy, Neutropenia, Gastroenterology, Dexamethasone, Antibodies, Monoclonal, Murine-Derived, Young Adult, Autologous stem-cell transplantation, Recurrence, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Aged, Retrospective Studies, Aged, 80 and over, Salvage Therapy, business.industry, Lymphoma, Non-Hodgkin, Cytarabine, Hematology, Middle Aged, medicine.disease, Oxaliplatin, Surgery, Treatment Outcome, Oncology, Drug Therapy, Combination, Female, Rituximab, business, medicine.drug
Abstract

Background Salvage therapy for patients with refractory/relapsed B-cell non-Hodgkin lymphoma (NHL) is based on polychemotherapy, followed by high-dose therapy and autologous stem cell transplantation in eligible patients (HDT/ASCT). R-DHAP combines rituximab with cisplatin, cytarabine, and dexamethasone. Patients and Methods We substituted cisplatin with oxaliplatin to avoid nephrotoxicity and retrospectively analyzed a large series of 91 patients with refractory/relapsed B-cell NHL to evaluate toxicities, response rates (RRs), and survival. Median age at R-DHAX (rituximab/dexamethasone/cytarabine/oxaliplatin) treatment was 60 years (range, 28-82 years). Renal insufficiency was present in 18 patients. The most frequent histologic subtypes were diffuse large B-cell lymphoma (n = 42) and follicular lymphoma (n = 30). Seventeen patients (19%) were naive to rituximab at time of R-DHAX. Results Grade III/IV toxicities were mainly hematologic, including anemia (n = 9), neutropenia (n = 44), and thrombocytopenia (n = 47). Grade I/II neurologic toxicities, sensitive or motor, were observed, and these were mainly transient except for 3 cases of motor neuropathy associated with previous exposure to vincristine. Neither renal toxicities nor degradation of previous renal insufficiency were observed. The overall RR was 75%, with a complete RR of 57%, with no statistical difference between patients previously treated with rituximab versus without rituximab. At a median follow-up of 23 months, 2-year probability rates of overall survival and progression-free survival were 75% and 43%, respectively, with a significant difference between patients treated with HDT/ASCT and patients not eligible for HDT/ASCT. Conclusion R-DHAX is an efficient regimen in patients with relapsed/refractory B-cell NHL even in elderly patients if hematologic toxicities are closely managed.

Published
2010
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39. Reduced versus full doses of irradiation after 3 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine in early stage Hodgkin lymphomas

Author

Nina, Arakelyan, Jean-Philippe, Jais, Vincent, Delwail, Josette, Brière, Marie-Pierre, Moles-Moreau, Delphine, Sénécal, Christian, Berthou, Bernard, Desablens, Pierre, Colonna, Jean-Marie, Andrieu, and Christiane, Ghando

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, Dacarbazine, Urology, Vinblastine, Bleomycin, chemistry.chemical_compound, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Doxorubicin, Aged, business.industry, Cancer, Radiotherapy Dosage, Middle Aged, medicine.disease, Combined Modality Therapy, Hodgkin Disease, Chemotherapy regimen, Lymphoma, Surgery, Oncology, ABVD, chemistry, Female, business, Follow-Up Studies, medicine.drug
Abstract

BACKGROUND: The combination of 3 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and a tailored, extended irradiation schedule has been used to treat patients with early Hodgkin lymphoma (HL) in the authors’ group since 1981. The randomized H97-E trial (1997-2004) was designed to assess the impact of a slightly reduced irradiation dose on the freedom from treatment failure (FFTF) rate. METHODS: Patients with supradiaphragmatic HL at clinical stages I and II who had � 2 affected lymph node areas and a mediastinal mass ratio

Published
2010
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40. Efficacy and toxicity of 2 schedules of frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone plus bortezomib in patients with B-cell lymphoma

Author

Nicolas Mounier, Josette Brière, Marjan Ertault, Pauline Brice, Christophe Fermé, Christian Gisselbrecht, Gilles Salles, Vincent Ribrag, Corinne Haioun, and Jean-Baptiste Golfier

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Vincristine, Lymphoma, B-Cell, Cyclophosphamide, medicine.medical_treatment, Gastroenterology, Drug Administration Schedule, Bortezomib, Antibodies, Monoclonal, Murine-Derived, Prednisone, hemic and lymphatic diseases, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Aged, Chemotherapy, business.industry, Antibodies, Monoclonal, Middle Aged, Antigens, CD20, medicine.disease, Boronic Acids, Surgery, Regimen, Oncology, Doxorubicin, Pyrazines, Female, Rituximab, business, Progressive disease, medicine.drug
Abstract

BACKGROUND: Bortezomib demonstrated promising activity in lymphomas. The authors conducted a randomized phase 2 trial of frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with the addition of bortezomib in patients with B-cell lymphoma. METHODS: Patients were randomized between 2 schedules of bortezomib, Arm A (Days 1, 4, 8, and 11) and Arm B (Days 1 and 8), combined with 6 cycles of R-CHOP. For the first patients (Step 1), bortezomib was given at a dose of 1 mg/m2 in Arm A and 1.3 mg/m2 in Arm B. For the next patients (Step 2), doses were increased to 1.3 mg/m2 and 1.6 mg/m2 in Arms A and B, respectively. The primary endpoint was the rate of complete response (CR) and unconfirmed CR (CR/CRu) after 6 cycles. RESULTS: Forty-nine patients were included in the study, and 41 patients (84%) achieved a CR/CRu, ie, 18 of 20 patients (90%) in Arm A and 23 of 29 patients (79%) in Arm B. There were 6 partial responses and 2 patients with progressive disease. Neurologic toxicity occurred in 21 patients (43%) and was grade 2 in 11 patients (7 patients in Step 2) and grade 3 in 10 patients (9 patients in Step 2). Other grade 3 and 4 toxicities included constipation (n = 1), infections (n = 3), and cardiac events (n = 2). Grade 3 and 4 thrombocytopenia and leucopenia occurred in 14% and 41% of cycles, respectively. CONCLUSIONS: R-CHOP + bortezomib was an effective regimen and produced an 84% CR rate. However, the dose-limiting neurotoxicity should be kept in mind for further trials with vinca alkaloids or other potentially neurotoxic drugs combination therapies. Cancer 2009. © 2009 American Cancer Society.

Published
2009
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41. Is sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp identical to inflammatory pseudotumour? Report of 16 cases

Author

A. Le Tourneau, Thierry Jo Molina, J.-F. Knopf, A. Mangnan-Marai, Josette Brière, S. Bendjaballah, Bettina Fabiani, C. Billotet, Josée Audouin, P. Gaulard, H. Sevestre, Béatrice Marmey, S. Prevot, Jacques Diebold, and Hans Konrad Müller-Hermelink

Subjects
Adult, Male, Angiomatosis, Pathology, medicine.medical_specialty, Histology, Spleen, Granuloma, Plasma Cell, Pathology and Forensic Medicine, Angioma, Young Adult, Fibrosis, parasitic diseases, medicine, Humans, Hamartoma, Aged, Aged, 80 and over, Loose connective tissue, Histiocytoma, Benign Fibrous, business.industry, Splenic Neoplasms, General Medicine, Middle Aged, medicine.disease, Immunohistochemistry, medicine.anatomical_structure, Splenic Red Pulp, Red pulp, Inflammatory pseudotumor, Female, business
Abstract

Aims: To report 16 cases of sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp. Methods and results: Patients were selected in two phases. An initial group of seven patients was diagnosed with SANT based on the presence of angiomatoid nodules. Sheets of inflammatory fibrosis were found in three patients, resembling inflammatory pseudotumour (IPT); nine further cases of IPT were reviewed. Angiomatoid nodules were detected, leading to the diagnosis of SANT in all cases. The splenic mass (10–150 mm in diameter) was polycyclic, composed of multiple small nodules of loose connective tissue comprising myofibroblasts and a dense network of capillaries as well as some remnants of sinuses. Collagenous fibrosis surrounded them. Bands or large sheets of fibrosis, infiltrated by various inflammatory cells, particularly polytypic plasmacytes, resembling IPT, were present in 10 cases. Conclusions: SANT of the red pulp is a distinct benign pseudotumorous lesion of the spleen characterized by the presence of angiomatoid nodules. We observed such angiomatoid nodules in all our cases of splenic IPT, which were not follicular dendritic cell or myofibroblastic tumours. We therefore recommend careful examination for angiomatoid nodules in all suspected cases of splenic IPT.

Published
2008
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42. Pediatric-Like Acute Lymphoblastic Leukemia Therapy in Adults With Lymphoblastic Lymphoma: The GRAALL-LYSA LL03 Study

Author

Patrice Chevallier, Carlos Graux, Vahid Asnafi, Anne Moreau, Thomas Vermeulin, Jacques Benichou, Gilles Salles, Stephanie Seris, Josette Brière, Norbert Ifrah, Aline Tanguy-Schmidt, Stéphane Leprêtre, Elizabeth Macintyre, Marie-Christine Béné, Jean-Michel Picquenot, Aurore Touzart, Serge Bologna, Reda Bouabdallah, Valérie Tallon-Simon, Françoise Huguet, Emmanuel Raffoux, Thierry Lamy, Hervé Dombret, 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 ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Charles Nicolle [Tunis], Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie ( UNIROUEN ), HEMATOLOGIE, CRLCC Henri Becquerel, Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'hématologie clinique, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre Hospitalier Universitaire de Purpan ( CHU Purpan ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Département d'Hematologie, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Cliniques Universitaires UCL de Mont-Godinne, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), The study was supported by a grant from the French Ministry of Health (Projet Hospitalier de Recherche Clinique of France [PHRC 2003 No. 13-2]). The Macintyre laboratory was supported by the Fondation de France, the Association de Recherche sur le Cancer, Cent pour Sang la Vie, and the Société Française des Cancers de l’Enfant. CHUGAI PHARMA France provided technical and financialsupport., 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), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Unité de biostatistiques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de 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), Université de Rennes (UR)-Hôpital Pontchaillou, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité de biostatistiques [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), 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)-CHU Necker - Enfants Malades [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Centre Hospitalier Universitaire de Purpan (CHU Purpan), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Université Toulouse III - Paul Sabatier ( UPS ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Bernardo, Elizabeth

Subjects
Male, Cancer Research, F-Box-WD Repeat-Containing Protein 7, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Phases of clinical research, Cell Cycle Proteins, Hematopoietic stem cell transplantation, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Gastroenterology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Central Nervous System Diseases, Recurrence, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Young adult, Receptor, Notch1, Prospective cohort study, Hematopoietic Stem Cell Transplantation, Induction Chemotherapy, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, Survival Rate, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, Adolescent, Ubiquitin-Protein Ligases, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Maintenance Chemotherapy, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, medicine, Humans, Survival rate, [ SDV ] Life Sciences [q-bio], L-Lactate Dehydrogenase, business.industry, F-Box Proteins, Lymphoblastic lymphoma, PTEN Phosphohydrolase, Induction chemotherapy, medicine.disease, Surgery, Consolidation Chemotherapy, ras Proteins, business, 030215 immunology
Abstract

Purpose This study evaluated the efficacy of pediatric-like acute lymphoblastic leukemia (ALL) therapy in adults with lymphoblastic lymphoma (LL). Patients and Methods This was a prospective phase II study in adults 18 to 59 years old with previously untreated LL. Patients were treated with an adapted pediatric-like ALL protocol, which included a corticosteroid prephase, a five-drug induction reinforced by sequential cyclophosphamide administration, dose-dense consolidation, late intensification, CNS prophylaxis, and a 2-year maintenance phase. Treatment response was assessed by computed tomography and optional positron emission tomography. Allogeneic hematopoietic stem cell transplant was offered to selected patients in first complete remission (CR) or unconfirmed CR. Results The study enrolled 148 patients (131 with T-lineage LL [T-LL] and 17 with B-lineage LL [B-LL]). A total of 119 patients with T-LL (90.8%) and 13 with B-LL (76.5%) reached CR/unconfirmed CR, including 26 with T-LL and two with B-LL who needed a second induction salvage course. Relapse occurred in 34 patients with T-LL and four with B-LL. In patients with T-LL, 3-year event-free survival was 63.3% (95% CI, 54.2% to 71.0%), disease-free survival was 72.4% (95% CI, 63.0% to 79.7%), and overall survival was 69.2% (95% CI, 60.0% to 76.7%). Multivariate analysis identified serum lactate dehydrogenase level and the NOTCH1/FBXW7/RAS/PTEN oncogene (a four-gene oncogenetic classifier) status but not positron emission tomography or hematopoietic stem cell transplant as independent prognostic factors for outcome in T-LL. Conclusion In adults with LL, an intensive pediatric-like ALL treatment protocol was associated with a good response rate and outcome. In patients with T-LL, the four-gene oncogenetic classifier and lactate dehydrogenase level were independent prognostic indicators.

Published
2016
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43. Evidence for a Multiclonal Origin of Multicentric Advanced Lesions of Kaposi Sarcoma

Author

Renan Duprez, Oumkaltoum Hbid, Antoine Gessain, Michel Huerre, Jean-Louis Essame Oyono, Patricia Tortevoye, Blaise Nkegoum, Marie-Jeanne Lando, Dominique Sainte-Marie, Josette Brière, Pierre Couppié, Eric Kassa-Kelembho, Céleste Lebbé, Vincent Lacoste, Camille Francès, Antoine Mahé, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Dermatologie, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur de Bangui, Réseau International des Instituts Pasteur (RIIP), Service de Médecine et d'Anatomopathologie, CHU de Yaoundé, Service d'Anatomopathologie, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur du Maroc, Institut d'Hygiène Sociale, Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Histotechnologie et Pathologie, Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP), 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), Hôpital de Cayenne, CHU Pitié-Salpêtrière [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
Male, Cancer Research, Pathology, viruses, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Child, Gammaherpesvirinae, Child, Lymph node, Skin, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, medicine.diagnostic_test, Middle Aged, Viral Load, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Herpesvirus 8, Human, Monoclonal, Female, Sarcoma, MESH: Viral Load, Viral load, Adult, medicine.medical_specialty, Adolescent, Biology, 03 medical and health sciences, MESH: Skin, Biopsy, medicine, Humans, Sarcoma, Kaposi, Aged, 030304 developmental biology, MESH: Adolescent, MESH: Herpesvirus 8, Human, MESH: Humans, MESH: Clone Cells, Cancer, MESH: Adult, medicine.disease, biology.organism_classification, MESH: Male, Clone Cells, MESH: DNA, Viral, Tonsil, DNA, Viral, MESH: Sarcoma, Kaposi, MESH: Female
Abstract

International audience; BACKGROUND: Kaposi sarcoma (KS) is a complex tumor of uncertain clonality. Studying the viral clonality of the human herpesvirus 8 (HHV-8) in KS to determine clonality of the tumors, a strategy that has been used previously with Epstein-Barr virus and its associated tumors, may elucidate whether multicentric (disseminated) KS lesions correspond to metastatic lesions or to expansions of independent clones. METHODS: A series of 139 KS biopsies (from skin, lymph node, or tonsil) was obtained from 98 patients, with 59 biopsies from 18 patients with disseminated multicentric KS skin lesions. The degree of spindle cell infiltration in biopsies was established by direct observation of hematoxylin-eosin-stained sections, and HHV-8 viral load was quantified by real-time polymerase chain reaction. To determine cellular clonality, the size heterogeneity of the HHV-8-fused terminal repeat (TR) region was determined by probing of electrophoresed restricted genomic DNA from KS biopsies for the HHV-8 TR sequence. RESULTS: HHV-8 clonality analysis was performed on the 62 samples for which sufficient DNA was obtained. Most samples corresponded to histologically nodular lesions with high spindle cell infiltration and high viral load. A clonal HHV-8 pattern was determined for 59 samples; 11 were found to be monoclonal and 48 to be oligoclonal. The informative samples that were from disseminated KS skin lesions (n = 26, from six patients) were either monoclonal or oligoclonal, and the size of HHV-8 episomes varied between these samples. CONCLUSION: Although some tumor KS lesions were monoclonal expansions of HHV-8-infected spindle cells, most advanced lesions were oligoclonal proliferations. Furthermore, individual KS disseminated tumor skin lesions were found to represent distinct expansions of HHV-8-infected spindle cells. Thus, our results suggest that KS lesions, especially in patients with advanced skin tumors, are reactive proliferations rather than true malignancies with metastatic dissemination.

Published
2007
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44. Plasma Cytokine and Soluble Receptor Signature Predicts Outcome of Patients With Classical Hodgkin's Lymphoma: A Study From the Groupe d'Etude des Lymphomes de l'Adulte

Author

Jean-Yves Blay, Josette Brière, Monique Grandjean, Franck Morschhauser, Pierre Lederlin, Christophe Fermé, Jean Gabarre, Nicolas Mounier, Jacques Bienvenu, Gilles Salles, Marine Divine, Aspasia Stamatoullas, Michel Guiguet, Pauline Brice, Rene-Olivier Casasnovas, Laurent Voillat, and Liliane Intrator

Subjects
Adult, Cancer Research, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Gastroenterology, Soluble cd30, Internal medicine, Blood plasma, medicine, Humans, Prospective Studies, Receptors, Cytokine, Receptor, Aged, Aged, 80 and over, business.industry, Plasma levels, Middle Aged, medicine.disease, Hodgkin Disease, Survival Analysis, Classical Hodgkin's Lymphoma, Lymphoma, Treatment Outcome, Endocrinology, Cytokine, Oncology, Multivariate Analysis, Cytokines, Tumor necrosis factor alpha, business
Abstract

Purpose Approximately 15% of patients with localized and 30% with disseminated classical Hodgkin's lymphoma fail to respond or relapse after first-line treatment. Usual prognosis scoring systems are actually unable to identify this small subset of patients with good confidence, pointing out the need for additional prognostic biomarkers. Patients and Methods We prospectively analyzed the prognosis value of plasma levels of tumor necrosis factor (TNF), its soluble receptors TNF-R1 and TNF-R2, IL-10, IL1-RA, IL-6, and soluble CD30 (sCD30) when taken before any treatment in 519 consecutive patients with a first diagnosis of classical Hodgkin's lymphoma. Results Levels of TNFα higher than 46 pg/mL, TNF-R1 higher than 3 ng/mL, TNF-R2 higher than 5 ng/mL, IL-10 higher than 30 pg/mL, IL1-RA higher than 668 pg/mL, IL-6 higher than 30 pg/mL, and sCD30 higher than 80 U/mL were associated with poor event-free and overall survival. In multivariate analysis, high levels of IL1-RA, IL-6, and sCD30 were independent poor prognosis factors, and the cytokine signature based on their combination allowed the stratification of patients in four prognosis classes, reaching a 5-year event-free survival probability of 92%, 85%, 76%, and 15%, respectively. This index was more potent than other scoring systems to predict patient event-free survival, and remained independent from the international prognostic score (P < .001), adding significant prognostic information to its predictive power. Conclusion Plasma cytokine signature is sufficient to predict disease-related outcome in classical Hodgkin's lymphoma, and allows the identification of patients with very high risk of treatment failure.

Published
2007
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45. MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study

Author

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)

Subjects
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
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46. High-dose cytarabine does not overcome the adverse prognostic value of CDKN2A and TP53 deletions in mantle cell lymphoma

Author

Corinne Haioun, Marie-Hélène Delfau-Larue, Gilles Salles, Wolfram Klapper, Fabrice Jardin, Elizabeth Macintyre, Eva Hoster, Catherine Thieblemont, Josette Brière, Christiane Pott, Olivier Casasnovas, Vincent Ribrag, Martin Dreyling, Michael Unterhalt, Pierre Feugier, Françoise Berger, Olivier Hermine, Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Hematopathology, Schleswig-Holstein University Hospitals, Hospices Civils de Lyon (HCL), 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), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (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 d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'hématologie clinique, Hématopoïèse normale et pathologique (U1170 Inserm), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Department of Internal Medicine III, University of Munich, Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], University Hospital Schleswig–Holstein, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Department of Pathology, Hematopathology Section and Lymph Node Registry, Universityhospital Schleswig-Holstein, Campus Kiel, 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 ( 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 ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Hématologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris Diderot - Paris 7 ( UPD7 ), III. Medizinische Klinik, Technische Universität München [München] ( TUM ), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Hospices Civils de Lyon ( HCL ), Centre Léon Bérard [Lyon], 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)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Pathology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Gene Dosage, Kaplan-Meier Estimate, Lymphoma, Mantle-Cell, Hematopoietic stem cell transplantation, Biology, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, International Prognostic Index, CDKN2A, Internal medicine, medicine, Humans, Autografts, neoplasms, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, 0303 health sciences, Genes, p16, Hazard ratio, Cytarabine, Hematopoietic Stem Cell Transplantation, Antineoplastic Protocols, Cell Biology, Hematology, Middle Aged, Genes, p53, Prognosis, medicine.disease, 3. Good health, Lymphoma, Ki-67 Antigen, 030220 oncology & carcinogenesis, Female, Mantle cell lymphoma, Gene Deletion, medicine.drug
Abstract

International audience; We revisited the prognostic value of frequently detected somatic gene copy number alterations (CNAs) in mantle cell lymphoma (MCL) patients treated first line with immunochemotherapy and autologous stem cell transplantation (ASCT), with or without high-dose cytarabine, in the randomized European MCL Younger trial. DNA extracted from tumor material of 135 patients (median age, 56 years) was analyzed by multiplex ligation-dependent probe amplification and/or quantitative multiplex polymerase chain reaction of short fluorescent fragments. As expected, MYC (18%) was the more frequently gained, whereas RB1 (26%), ATM (25%), CDKN2A (p16) (25%), and TP53 (22%) were the more frequently deleted. Whether adjusted for MCL International Prognostic Index (MIPI) or not, deletions of RB1, CDKN2A, TP53, and CDKN1B were associated with shorter overall survival (OS), similarly in both treatment arms, whereas CNAs in MYC, ATM, CDK2, CDK4, and MDM2 had no prognostic value. Additive effects were seen for CDKN2A (hazard ratio, 2.3; P = .007, MIPI-adjusted) and TP53 deletions (hazard ratio, 2.4; P = .007), reflected in a dismal outcome with simultaneous deletions (median OS, 1.8 years) compared with single deletions (median OS, 4.3 and 5.1 years) or without these deletions (median OS, 7 years), again similarly in both treatment arms. The additive prognostic effects of CDKN2A and TP53 deletions were independent of the Ki-67 index. Despite immunochemotherapy, high-dose cytarabine, and ASCT, younger MCL patients with deletions of CDKN2A (p16) and TP53 show an unfavorable prognosis and are candidates for alternative therapeutic strategies. This trial was registered at www.clinicaltrials.gov as #NCT00209222.

Published
2015
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47. Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials

Author

Nadine Martin-Garcia, Philippe Gaulard, Karim Belhadj, Nicolas Mounier, Stéphane Cheze, Jean Alain Kummer, Felix Reyes, Vincent Ribrag, Françoise Berger, Céline Bossard, Josette Brière, Anne-Catherine Baglin, Jacques Bosq, and Christian Gisselbrecht

Subjects
Adult, Male, medicine.medical_specialty, Pathology, T-Lymphocytes, Immunology, Nose, Lymphoma, T-Cell, Biochemistry, Gastroenterology, Granzymes, International Prognostic Index, Internal medicine, medicine, Humans, T-cell lymphoma, Serpins, Aged, Univariate analysis, Hematology, business.industry, Cell Biology, Middle Aged, Prognosis, Natural killer T cell, medicine.disease, Lymphoma, Killer Cells, Natural, Survival Rate, Granzyme B, Phenotype, Treatment Outcome, Drug Therapy, Combination, Female, business, Chemoradiotherapy
Abstract

Nasal NK/T-cell lymphoma is a rare disease entity with a poor outcome. Expression of antiapoptotic proteins has not been extensively investigated in this entity. Forty-eight patients with nasal T/NK-cell lymphoma who received first-line polychemotherapy (n = 44) or chemoradiotherapy (n = 4) were analyzed for expression of active caspase-3 (aC3), granzyme B protease inhibitor 9 (PI9), and Bcl-2 proteins. Lymphomas were CD3+/CD5−/granzyme B+ and EBV-associated. Median age was 46 years. Stage I/II disease was present in 75% of the cases and an International Prognostic Index (IPI) score less than 1 in 65%. With a median follow-up of 6.3 years, 5-year event-free survival (EFS) and overall survival (OS) rates were 39% and 49%, respectively. Apoptotic index was scored as high in 32% of cases and PI9 expression as positive in 68%, whereas 35% disclosed a high number of aC3+ tumor cells. Univariate analysis showed that absence of PI9 and low apoptotic index were associated with poor outcome, but not aC3 expression nor IPI score. By multivariate analysis, both parameters affected independently EFS (P = .02 and .08, respectively) and OS (P = .009 and .04). In view of its constitutive expression by normal NK cells, it is suggested that loss of PI9 expression in tumor cells may reflect some mechanism associated with progression.

Published
2006
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48. How to define intermediate stage in Hodgkin's lymphoma?

Author

Christian Gisselbrecht, O. Casanovas, Oumedaly Reman, Christophe Fermé, Pauline Brice, Nicolas Mounier, Marine Divine, C. Sebban, Josette Brière, Christophe Hennequin, and Marc André

Subjects
Oncology, medicine.medical_specialty, education.field_of_study, Scoring system, business.industry, Population, Hematology, General Medicine, medicine.disease, Hodgkin's lymphoma, Lymphoma, Surgery, Intermediate stage, B symptoms, Internal medicine, medicine, Stage (cooking), medicine.symptom, education, business, Survival analysis
Abstract

BACKGROUND Intermediate or unfavourable stage Hodgkin's lymphoma (HL) definition relies upon at least three different scoring systems defined by cooperative groups (EORTC, GHSG and Canadian-ECOG). We aimed to investigate their efficacy and their correlation with International Prognostic Score (IPS) for advanced HL. PATIENTS AND METHODS We studied a population of 1156 patients with localized stage HL treated prospectively within GELA centres in H8 (518 patients) and H9 (638 patients) protocols. Median age: 30 yr, 18%, Female 50%; stage I: 25%; stage II: 75%. According to scoring systems 70% had 0-1 EORTC factors; 60% 0-1 GHSG factors and 82% 0-1 Canadian factors. The IPS for advanced stages was available only in H9 study with 64% 0-1 factor. RESULTS Survival curves according to each of the different scoring systems could significantly discriminate the subgroup populations. When a multivariate Cox analysis was performed for overall survival (OS) including all the scoring system variables: age > 45 yr, sex male, Haemoglobin < 10.5 g/dL, lymphocytes < 600/microL, B symptoms with elevated ESR, extra nodal sites did retain an independent significant value. Probability of OS was 99%, 98%, 92%, 82% and 73% for patients with 1-5 factors, respectively P < 0.0001. CONCLUSION These factors are similar for most of them with those described in the IPS when stages III and IV are replaced by extra nodal localization. This new score should be validated in other prospective trials, as it will simplify the Hodgkin prognostic scoring systems for localized and advanced stages.

Published
2005
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49. Pegylated liposomal doxorubicin: an efficient treatment in patients with Hodgkin lymphoma relapsing after high dose therapy and stem cell transplation

Author

Bénédicte D’Eau, Isabelle Madelaine, Patricia Franchi, Thomas Clozel, Catherine Thieblemont, Eric de Kerviler, Pauline Brice, Marie Robin, Claire Benet, and Josette Brière

Subjects
Adult, Male, Adolescent, business.industry, Hematology, Middle Aged, Hodgkin Disease, Polyethylene Glycols, Pegylated Liposomal Doxorubicin, Young Adult, High dose therapy, Doxorubicin, Recurrence, Cancer research, Humans, Medicine, Hodgkin lymphoma, Female, In patient, Stem cell, business, Neoplasm Staging, Retrospective Studies, Stem Cell Transplantation
Published
2013
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50. Another look at follicular lymphoma: immunophenotypic and molecular analyses identify distinct follicular lymphoma subgroups

Author

Josette Brière, Pierre Sujobert, Corinne Haioun, Peter G. Isaacson, William Townsend, Asim Khwaja, Hongxiang Liu, David C. Linch, Christiane Copie-Bergman, Thomas M. Grogan, Jennifer C. Paterson, Teresa Marafioti, Andrew Clear, Alan D. Ramsay, Stefano Pileri, Philippe Gaulard, Claudio Agostinelli, Vishvesh H. Shende, Noraidah Masir, Maryse Baia, Kandavel Shanmugam, Elizabeth Nacheva, Ming-Qing Du, Kirit M. Ardeshna, Maria Calaminici, Pier Paolo Piccaluga, John G. Gribben, Simon P. Brooks, Teresa Marafioti, Christiane Copie-Bergman, Maria Calaminici, Jennifer C Paterson, Vishvesh H Shende, Hongxiang Liu, Maryse Baia, Alan D Ramsay, Claudio Agostinelli, Josette Brière, Andrew Clear, Ming-Qing Du, Pier Paolo Piccaluga, Noraidah Masir, Elizabeth P Nacheva, Pierre Sujobert, Kandavel Shanmugam, Thomas M Grogan, Simon P Brook, Asim Khwaja, Kirit Ardeshna, William Townsend, Stefano A Pileri, Corinne Haioun, David Linch, John G Gribben, Philippe Gaulard, and Peter G Isaacson

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Histology, phenotype, bcl-2, Follicular lymphoma, Biology, Pathology and Forensic Medicine, Immunophenotyping, follicular lymhpoma, Diagnosis, Differential, Young Adult, FISH, immune system diseases, hemic and lymphatic diseases, Follicular phase, medicine, Biomarkers, Tumor, Humans, music, Lymphoma, Follicular, B cell, In Situ Hybridization, Fluorescence, Aged, Aged, 80 and over, Gene Rearrangement, music.instrument, General Medicine, Gene rearrangement, Lymphoma, B-Cell, Marginal Zone, Middle Aged, medicine.disease, Marginal zone, Follicular hyperplasia, Lymphoma, Genes, bcl-2, DNA-Binding Proteins, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, immunohistochemistry, Proto-Oncogene Proteins c-bcl-6, Stathmin, Female, Neprilysin
Abstract

Aims: The aim of this study was to analyse the immunophenotypic and molecular features of a large series of follicular lymphomas, focusing in particular on atypical cases that fail to express CD10 and/or bcl-2. Such cases present diagnostic pitfalls, especially with regard to the differential diagnosis from follicular hyperplasia and marginal zone B-cell lymphoma. Therefore, we also included an immunohistochemical evaluation of stathmin, which is strongly expressed by germinal centre B cells, as a putative new marker for follicular lymphomas, particularly those with an atypical phenotype. Methods and results: Two hundred and five follicular lymphomas were investigated with immunohistochemistry and fluorescence in-situ hybridization (FISH). The use of three distinct anti-bcl-2 antibodies together with CD10 expression data and FISH analysis for bcl-2 and bcl-6 rearrangements allowed subclassification of follicular lymphoma into four distinct subgroups: (i) CD10-positive/bcl-2-positive, (ii) CD10-positive/bcl-2-negative, (iii) CD10-negative/bcl-2-positive, and (iv) CD10-negative/bcl-2-negative. All cases were bcl-6-positive. STMN1 (stathmin) was shown to be helpful in diagnosing bcl-2-negative and/or CD10-negative follicular lymphomas, and in their distinction from marginal zone B-cell lymphoma. Conclusions: Combined immunohistological and molecular analyses reveal that follicular lymphomas showing an atypical immunophenotypic and molecular profile exist, and we demonstrate that STMN1 represents a novel useful diagnostic marker for these. © 2013 Blackwell Publishing Ltd.

Published
2012

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