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

Author: Sylvain Carras, Alexia Torroja, Anouk Emadali, Emilie Montaut, Nicolas Daguindau, Adrian Tempescul, Anne Moreau, Emmanuelle Tchernonog, Anna Schmitt, Roch Houot, Caroline Dartigeas, Sarah Barbieux, Selim Corm, Anne Banos, Ludovic Fouillet, Jehan Dupuis, Margaret Macro, Joel Fleury, Fabrice Jardin, Clementine Sarkozy, Ghandi Damaj, Pierre Feugier, Luc Matthieu Fornecker, Cecile Chabrot, Veronique Dorvaux, Krimo Bouabdallah, Sandy Amorim, Reda Garidi, Laurent Voillat, Bertrand Joly, Nadine Morineau, Marie Pierre Moles, Hacene Zerazhi, Jean Fontan, Yazid Arkam, Magda Alexis, Vincent Delwail, Jean Pierre Vilque, Loic Ysebaert, Barbara Burroni, Mary Callanan, Steven Le Gouill, and Rémy Gressin
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Between 2011 and 2012, a phase II trial evaluated the use of the RiBVD (rituximab, bendamustine, velcade and dexamethasone) combination as first-line treatment for mantle cell lymphoma (MCL) patients over the age of 65. We have now re-examined the classic prognostic factors, adding an assessment of TP53 mutation status. Patients (N=74; median age 73 years) were treated with the RiBVD combination. Median progression-free survival (mPFS) was 79 months and median overall survival (mOS) was 111 months. TP53 mutation status was available for 54/74 (73%) patients. TP53 mutations (TP53mt) were found in 12 patients (22.2%). In multivariate analysis, among the prognostic factors (PF) evaluated, only TP53mt and an albumin level (Alb) 3.6 g/dL were independently associated with a shorter mPFS. A hazard ratio (HR) of 3.16 (1.3-9.9, P=0.014) was obtained for TP53mt versus TP53 wild-type (wt), and 3.6 (1.39-9.5, P=0.009) for Alb
Published: 2023
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2. SARS-CoV-2 Infection in Patients With Waldenström’s Macroglobulinemia: A Multicenter International Cohort Study

Author: Irene Defrancesco, Virginia Valeria Ferretti, Pierre Morel, Charalampia Kyriakou, Efstathios Kastritis, Ibrahim Tohidi-Esfahani, Alessandra Tedeschi, Christian Buske, Ramón García-Sanz, Josephine M.I. Vos, Veronica Peri, Gloria Margiotta Casaluci, Angela Ferrari, Francesco Piazza, Rimke Oostvogels, Ester Lovato, Lydia Montes, Luc Matthieu Fornecker, Alexander Grunenberg, Meletios Athanasios Dimopoulos, Constantine S. Tam, Shirley D’Sa, Veronique Leblond, Judith Trotman, Francesco Passamonti, Luca Arcaini, Marzia Varettoni, and on behalf of the European Consortium for Waldenström’s Macroglobulinemia
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2023
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3. A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma

Author: Rémy Gressin, Nicolas Daguindau, Adrian Tempescul, Anne Moreau, Sylvain Carras, Emmanuelle Tchernonog, Anna Schmitt, Roch Houot, Caroline Dartigeas, Jean Michel Pignon, Selim Corm, Anne Banos, Christiane Mounier, Jehan Dupuis, Margaret Macro, Joel Fleury, Fabrice Jardin, Clementine Sarkozy, Ghandi Damaj, Pierre Feugier, Luc Matthieu Fornecker, Cecile Chabrot, Veronique Dorvaux, Krimo Bouadallah, Sandy Amorin, Reda Garidi, Laurent Voillat, Bertrand Joly, Philippe Solal Celigny, Nadine Morineau, Marie Pierre Moles, Hacene Zerazhi, Jean Fontan, Yazid Arkam, Magda Alexis, Vincent Delwail, Jean Pierre Vilque, Loic Ysebaert, Steven Le Gouill, Mary B. Callanan, and for the Lymphoma Study Association
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: We present results of a prospective, multicenter, phase II study evaluating rituximab, bendamustine, bortezomib and dexamethasone as first-line treatment for patients with mantle cell lymphoma aged 65 years or older. A total of 74 patients were enrolled (median age, 73 years). Patients received a maximum of six cycles of treatment at 28-day intervals. The primary objective was to achieve an 18-month progression-free survival rate of 65% or higher. Secondary objectives were to evaluate toxicity and the prognostic impact of mantle cell lymphoma prognostic index, Ki67 expression, [18F]fluorodeoxyglucose-positron emission tomography and molecular minimal residual disease, in peripheral blood or bone marrow. With a median follow-up of 52 months, the 24-month progression-free survival rate was 70%, hence the primary objective was reached. After six cycles of treatment, 91% (54/59) of responding patients were analyzed for peripheral blood residual disease and 87% of these (47/54) were negative. Four-year overall survival rates of the patients who did not have or had detectable molecular residual disease in the blood at completion of treatment were 86.6% and 28.6%, respectively (P
Published: 2019
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4. Clinical presentation, outcome, and prognostic markers in patients with intravascular large B‐cell lymphoma, a lymphoma study association (LYSA) retrospective study

Author: Antoine Bonnet, Céline Bossard, Ludovic Gabellier, Julien Rohmer, Othman Laghmari, Marie Parrens, Clémentine Sarkozy, Rémy Dulery, Virginie Roland, Francisco Llamas‐Gutierrez, Lucie Oberic, Luc‐Matthieu Fornecker, Laura Bounaix, Bruno Villemagne, Vanessa Szablewski, Sylvain Choquet, Krimo Bouabdallah, Alexandra Traverse‐Glehen, Mohamad Mohty, Laurence Sanhes, Roch Houot, Thomas Gastinne, Christophe Leux, and Steven Le Gouill
Subjects: autoimmune disorders, BCL2 expression, intravascular lymphoma, nodal involvement, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Intravascular large B‐cell lymphoma (lVLBCL) is a very rare type of large B‐cell lymphoma. Methods We conducted a retrospective study on IVLBCL patients treated from 2000 to 2016 in LYSA cooperative group centers. Results Sixty‐five patients were identified in 23 centers. Median age at diagnosis was 69 years (range 23–92). Thirty‐four patients (64%) had an IPI score >3 and 40 patients (67%) had a performance status ≥2. The most frequent extra‐nodal locations were bone marrow (n = 34; 52%), central nervous system (n = 25; 39%), and skin (n = 21; 33%). Nodal involvement and endocrine system were observed in 34% (n = 22) and 18% (n = 12) of all cases, respectively. Twenty‐six patients (41%) had macrophage activation syndrome. Tumor cells were frequently CD5 positive (52%) with a non‐germinal center origin (86%). BCL2 was expressed in 87% of all samples analyzed (n = 20) and 43% of patients had a MYC/BCL2 double expression. Fifty‐six patients were treated with a regimen of chemotherapy containing rituximab, among whom 73% reached complete remission. The median progression‐free survival (PFS) and median overall survival (OS) were 29.4 months and 63.8 months, respectively. History of autoimmune disorder (Hazard ratio [HR] 3.3 [1.4–7.8]; p
Published: 2022
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5. A French multicentric prospective prognostic cohort with epidemiological, clinical, biological and treatment information to improve knowledge on lymphoma patients: study protocol of the 'REal world dAta in LYmphoma and survival in adults' (REALYSA) cohort

Author: Hervé Ghesquières, Cédric Rossi, Fanny Cherblanc, Sandra Le Guyader-Peyrou, Fontanet Bijou, Pierre Sujobert, Pascale Fabbro-Peray, Adeline Bernier, Aurélien Belot, Loic Chartier, Luc-Matthieu Fornecker, Isabelle Baldi, Krimo Bouabdallah, Camille Laurent, Lucie Oberic, Nadine Morineau, Steven Le Gouill, Franck Morschhauser, Corinne Haioun, Gandhi Damaj, Stéphanie Guidez, Gaëlle Labouré, Olivier Fitoussi, Laure Lebras, Rémy Gressin, Gilles Salles, Loïc Ysebaert, and Alain Monnereau
Subjects: Cohort study, Outcomes, Lymphoma patients, Real life, France, Public aspects of medicine, RA1-1270
Abstract: Abstract Background Age-adjusted lymphoma incidence rates continue to rise in France since the early 80’s, although rates have slowed since 2010 and vary across subtypes. Recent improvements in patient survival in major lymphoma subtypes at population level raise new questions about patient outcomes (i.e. quality of life, long-term sequelae). Epidemiological studies have investigated factors related to lymphoma risk, but few have addressed the extent to which socioeconomic status, social institutional context (i.e. healthcare system), social relationships, environmental context (exposures), individual behaviours (lifestyle) or genetic determinants influence lymphoma outcomes, especially in the general population. Moreover, the knowledge of the disease behaviour mainly obtained from clinical trials data is partly biased because of patient selection. Methods The REALYSA (“REal world dAta in LYmphoma and Survival in Adults”) study is a real-life multicentric cohort set up in French areas covered by population-based cancer registries to study the prognostic value of epidemiological, clinical and biological factors with a prospective 9-year follow-up. We aim to include 6000 patients over 4 to 5 years. Adult patients without lymphoma history and newly diagnosed with one of the following 7 lymphoma subtypes (diffuse large B-cell, follicular, marginal zone, mantle cell, Burkitt, Hodgkin, mature T-cell) are invited to participate during a medical consultation with their hematologist. Exclusion criteria are: having already received anti-lymphoma treatment (except pre-phase) and having a documented HIV infection. Patients are treated according to the standard practice in their center. Clinical data, including treatment received, are extracted from patients’ medical records. Patients’ risk factors exposures and other epidemiological data are obtained at baseline by filling out a questionnaire during an interview led by a clinical research assistant. Biological samples are collected at baseline and during treatment. A virtual tumor biobank is constituted for baseline tumor samples. Follow-up data, both clinical and epidemiological, are collected every 6 months in the first 3 years and every year thereafter. Discussion This cohort constitutes an innovative platform for clinical, biological, epidemiological and socio-economic research projects and provides an opportunity to improve knowledge on factors associated to outcome of lymphoma patients in real life. Trial registration 2018-A01332–53, ClinicalTrials.gov identifier: NCT03869619 .
Published: 2021
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6. Efficacy of Serotherapy on an N501Y Variant of SARS-CoV-2 in a Patient With Chronic Lymphocytic Leukemia

Author: Colin Vercueil, Lauriane Eberst, Catherine Humbrecht, and Luc-Matthieu Fornecker
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2021
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7. Efficacy of a short sandwich protocol, methotrexate, gemcitabine, L‐asparaginase and dexamethasone chemotherapy combined with radiotherapy, in localised newly diagnosed <scp>NK</scp> /T‐cell lymphoma: A French retrospective study

Author: Sammara Chaubard, Amira Marouf, David Lavergne, François Lemonnier, Julien Rossignol, Aline Clavert, Rémy Gressin, Guillaume Cartron, Agathe Waultier‐Rascalou, Jacques Vargaftig, Gilles Salles, Emmanuel Bachy, Hervé Ghesquières, Olivier Tournilhac, Adrien Chauchet, Steven Le Gouill, Gandhi Damaj, Luc‐Matthieu Fornecker, David Sibon, Lucie Obéric, Jean‐Marie Michot, Philippe Gaulard, Olivier Hermine, Lucile Couronné, and Arnaud Jaccard
Subjects: Hematology
Published: 2023
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8. Microenvironment Remodeling and Subsequent Clinical Implications in Diffuse Large B-Cell Histologic Variant of Richter Syndrome

Author: Hélène Augé, Anne-Béatrice Notarantonio, Romain Morizot, Anne Quinquenel, Luc-Matthieu Fornecker, Sébastien Hergalant, Pierre Feugier, and Julien Broséus
Subjects: Richter syndrome, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, genomics, microenvironment, immune checkpoint, Immunologic diseases. Allergy, RC581-607
Abstract: IntroductionRichter Syndrome (RS) is defined as the development of an aggressive lymphoma in the context of Chronic Lymphocytic Leukemia (CLL), with a Diffuse Large B-Cell Lymphoma (DLBCL) histology in 95% cases. RS genomic landscape shares only a few features with de novo DLBCLs and is marked by a wide spectrum of cytogenetic abnormalities. Little is known about RS microenvironment. Therapeutic options and efficacy are limited, leading to a 12 months median overall survival. The new targeted treatments usually effective in CLL fail to obtain long-term remissions in RS.MethodsWe reviewed available PubMed literature about RS genomics, PD-1/PD-L1 (Programmed Death 1/Programmed Death Ligand 1) pathway triggering and subsequent new therapeutic options.ResultsData from about 207 patients from four landmark papers were compiled to build an overview of RS genomic lesions and point mutations. A number of these abnormalities may be involved in tumor microenvironment reshaping. T lymphocyte exhaustion through PD-L1 overexpression by tumor cells and subsequent PD-1/PD-L1 pathway triggering is frequently reported in solid cancers. This immune checkpoint inhibitor is also described in B lymphoid malignancies, particularly CLL: PD-1 expression is reported in a subset of prolymphocytes from the CLL lymph node proliferation centers. However, there is only few data about PD-1/PD-L1 pathway in RS. In RS, PD-1 expression is a hallmark of recently described « Regulatory B-cells », which interact with tumor microenvironment by producing inhibiting cytokines such as TGF-β and IL-10, impairing T lymphocytes anti-tumoral function. Based upon the discovery of high PD-1 expression on tumoral B lymphocyte from RS, immune checkpoint blockade therapies such as anti-PD-1 antibodies have been tested on small RS cohorts and provided heterogeneous but encouraging results.ConclusionRS genetic landscape and immune evasion mechanisms are being progressively unraveled. New protocols using targeted treatments such as checkpoint inhibitors as single agents or in combination with immunochemotherapy are currently being evaluated.
Published: 2020
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9. Diagnosis and Treatment of Chronic Lymphocytic Leukemia: Recommendations of the French CLL Study Group (FILO)

Author: Anne Quinquenel, Thérèse Aurran-Schleinitz, Aline Clavert, Florence Cymbalista, Caroline Dartigeas, Frédéric Davi, Sophie de Guibert, Alain Delmer, Marie-Sarah Dilhuydy, Pierre Feugier, Luc-Matthieu Fornecker, David Ghez, Romain Guieze, Kamel Laribi, Véronique Leblond, Stéphane Leprêtre, Rémi Letestu, Vincent Lévy, Florence Nguyen-Khac, Anne-Sophie Michallet, Cécile Tomowiak, Olivier Tournilhac, Loïc Ysebaert, Xavier Troussard, and on the behalf of the FILO-LLC Group
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Abstract. As a result of significant recent developments, the management of patients with chronic lymphocytic leukemia (CLL) is changing, and new therapeutic options will continue to emerge in the near future. The recommendations of the French Innovative Leukemia Organization (FILO-CLL) group presented here are intended to provide practical recommendations for physicians taking care of CLL patients, taking into account the availability of both biological tests and therapies in daily practice in France at the time of publication. This text details the documented information and guidelines on diagnosis, indications for treatment, infectious complications and therapeutic strategies in frontline and relapsed CLL as well as in particular conditions such as autoimmune cytopenia or Richter syndrome.
Published: 2020
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10. Impact of TP53 mutations in acute myeloid leukemia patients treated with azacitidine.

Author: Pierre Bories, Naïs Prade, Stéphanie Lagarde, Bastien Cabarrou, Laetitia Largeaud, Julien Plenecassagnes, Isabelle Luquet, Véronique De Mas, Thomas Filleron, Manon Cassou, Audrey Sarry, Luc-Matthieu Fornecker, Célestine Simand, Sarah Bertoli, Christian Recher, and Eric Delabesse
Subjects: Medicine, Science
Abstract: Hypomethylating agents are a classical frontline low-intensity therapy for older patients with acute myeloid leukemia. Recently, TP53 gene mutations have been described as a potential predictive biomarker of better outcome in patients treated with a ten-day decitabine regimen., However, functional characteristics of TP53 mutant are heterogeneous, as reflected in multiple functional TP53 classifications and their impact in patients treated with azacitidine is less clear. We analyzed the therapeutic course and outcome of 279 patients treated with azacitidine between 2007 and 2016, prospectively enrolled in our regional healthcare network. By screening 224 of them, we detected TP53 mutations in 55 patients (24.6%), including 53 patients (96.4%) harboring high-risk cytogenetics. The identification of any TP53 mutation was associated with worse overall survival but not with response to azacitidine in the whole cohort and in the subgroup of patients with adverse karyotype. Stratification of patients according to three recent validated functional classifications did not allow the identification of TP53 mutated patients who could benefit from azacitidine. Systematic TP53 mutant classification will deserve further exploration in the setting of patients treated with conventional therapy and in the emerging field of therapies targeting TP53 pathway.
Published: 2020
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11. Tuberculosis and atypical mycobacterial infections in ruxolitinib-treated patients with primary or secondary myelofibrosis or polycythemia vera

Author: Sylvain Lescuyer, Marie-Pierre Ledoux, Simon Gravier, Shanti Natarajan-Amé, Céline Duval, Fréderic Maloisel, Laurent Mauvieux, Elise Toussaint, Luc-Matthieu Fornecker, and Raoul Herbrecht
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Ruxolitinib is a JAK-1/JAK-2 inhibitor indicated for the treatment of polycythemia vera and primary or secondary myelofibrosis. Only one patient (0.2%) was diagnosed with tuberculosis among the 485 patients receiving ruxolitinib in the four pivotal trials. Fourteen cases of tuberculosis have since been reported. We observed two (3%) mycobacterial infections (one due to Mycobacterium tuberculosis and one due to Mycobacterium avium complex) in our cohort of 65 patients receiving ruxolitinib. This observation suggests that the rate of mycobacterial infection might be higher than that observed in the pivotal trials and that atypical mycobacterial infections can also occur. Keywords: Ruxolitinib, Mycobacteria, Tuberculosis, Mycobacterium tuberculosis, Mycobacterium avium complex
Published: 2019
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12. Retrospective analysis of a cohort of 41 de novo B-cell prolymphocytic leukemia patients: impact of genetics and targeted therapies (a FILO study)

Author: Caroline Algrin, Louis Pérol, Elise Chapiro, Lucile Baseggio, Karim Maloum, Catherine Settegrana, Jean-François Lesesve, Justine Siavellis, Alain Delmer, Anne-Sophie Michallet, Emmanuelle Ferrant, Pierre Feugier, Cécile Tomowiak, Annie Brion, David Ghez, Luc-Matthieu Fornecker, Sarah Ivanoff, Stéphanie Struski, Laurent Sutton, Isabelle Radford-Weiss, Virginie Eclache, Christine Lefebvre, Véronique Leblond, Florence Nguyen-Khac, and Damien Roos-Weil
Subjects: Hematology
Published: 2022
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13. Bruton's tyrosine kinase (BTK) gene overexpression is associated with risk of lymphoma in primary Sjögren's syndrome

Author: Pierre‐Marie Duret, Cedric Schleiss, Lou Kawka, Nicolas Meyer, Tao Ye, Alain Saraux, Valérie Devauchelle‐Pensec, Raphaele Seror, Claire Larroche, Aleth Perdriger, Jean Sibilia, Laurent Vallat, Luc‐Matthieu Fornecker, Gaetane Nocturne, Xavier Mariette, and Jacques‐Eric Gottenberg
Subjects: Rheumatology, Immunology, Immunology and Allergy
Published: 2023
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14. Randomized Phase III Trial Evaluating Subcutaneous Rituximab for the First-Line Treatment of Low–Tumor Burden Follicular Lymphoma: Results of a LYSA Study

Author: Guillaume Cartron, Emmanuel Bachy, Hervé Tilly, Nicolas Daguindau, Gian-Matteo Pica, Fontanet Bijou, Christiane Mounier, Aline Clavert, Gandhi Laurent Damaj, Borhane Slama, Olivier Casasnovas, Roch Houot, Krimo Bouabdallah, David Sibon, Olivier Fitoussi, Nadine Morineau, Charles Herbaux, Thomas Gastinne, Luc-Matthieu Fornecker, Corinne Haioun, Vincent Launay, Carla Araujo, Omar Benbrahim, Laurence Sanhes, Remy Gressin, Hugo Gonzalez, Franck Morschhauser, David Ternant, Luc Xerri, Karin Tarte, and Delphine Pranger
Subjects: Cancer Research, Oncology
Abstract: PURPOSE Rituximab improves progression-free survival (PFS) and time to next treatment (TTNT) when compared with the watch and wait strategy for patients with low–tumor burden follicular lymphoma (FL). Prolonged rituximab maintenance did not prolong TTNT, whereas it raises concerns about resources use and patient adhesion. Our aim was then to investigate the use of short rituximab maintenance using the subcutaneous (SC) route in patients with low–tumor burden FL. METHODS Patients with histologically confirmed CD20+ low–tumor burden FL were randomly assigned to receive either rituximab, 375 mg/m2 once daily on D1, D8, D15, and D22, intravenous route (IV, control arm), or rituximab, 375 mg/m2, on day 1 (D1), IV followed by rituximab 1,400 mg total dose, SC once daily on D8, D15, and D22, with maintenance at months 3 (M3), M5, M7, and M9 (experimental arm). The primary end point was PFS. Secondary end points included safety, overall response rates, TTNT, and overall survival (OS). RESULTS Two hundred two patients with low–tumor burden FL were randomly assigned to the experimental (n = 100) or control arm (n = 102). The primary end point was met: the 4-year PFS was 58.1% (95% CI, 47.5 to 67.4) and 41.2% (95% CI, 30.6 to 51.6) in experimental and control arms, respectively (hazard ratio, 0.585 [0.393 to 0.871]; P = .0076). Complete response (CR) rates were 59.0% (95% CI, 48.7 to 68.7) in the experimental arm and 36.3% (95% CI, 27.0 to 46.4) in the control arm ( P = .001). TTNT and OS were not significantly different. CR was associated with longer PFS and TTNT. High rituximab exposure during the first three months was independently associated with higher CR, PFS, and TTNT. CONCLUSION SC rituximab improves PFS for patients with low–tumor burden FL when used in induction followed by short maintenance. High rituximab exposure during the first 3 months after treatment initiation is, however, the only parameter influencing patient outcomes.
Published: 2023
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15. A fixed-duration, immunochemotherapy approach in CLL: 5.5-year results from the phase 2 ICLL-07 FILO trial

Author: Anne-Sophie Michallet, Rémi Letestu, Magali Le Garff-Tavernier, Lydia Campos, Michel Ticchioni, Marie-Sarah Dilhuydy, Stephane MORISSET, Valerie Rouille, Beatrice Mahe, Kamel Laribi, Bruno Villemagne, Emmanuelle France Ferrant, Olivier Tournilhac, Alain Jacques Delmer, Lysiane Molina, Veronique Leblond, Cécile TOMOWIAK, Sophie De Guibert, Frederique Orsini Piocelle, Anne Banos, Philippe Carassou, Guillaume Cartron, Luc-Matthieu Fornecker, Loïc Ysebaert, Caroline Dartigeas, Malgorzata Truchan-Graczyk, Jean-Pierre Vilque, Thérèse Aurran Schleinitz, Florence Cymbalista, Stéphane Leprêtre, Vincent Lévy, Florence Nguyen-Khac, and Pierre Feugier
Subjects: Hematology
Abstract: In previously untreated, medically fit patients with chronic lymphocytic leukemia, research is focused on developing fixed-duration strategies to improve long-term outcomes whilst sparing patients from serious toxicities. The ICLL-07 trial evaluated a fixed-duration (15-month) immunochemotherapy approach where, following obinutuzumab-ibrutinib induction for 9 months, patients (n=10) in complete remission (CR) with bone marrow (BM) measurable residual disease (MRD)
Published: 2023
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16. Differential Phosphoproteomics Deciphers Physiopathology of High-Risk Mantle Cell Lymphoma

Author: Charline Fuseau, Mathieu Baldacini, Alina Nicolae, Laurent Miguet, Laurent Mauvieux, Laurent Vallat, Claire Domon-Dell, Manuela Tavian, Jean-Noel Freund, Sarah Cianferani, Christine Schaeffer-Reiss, Luc-Matthieu Fornecker, and Delphine C.M. Rolland
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022
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17. Blinatumomab for Patients with Richter Syndrome: Final Results of the Phase 2 Blinart Trial from the Filo Group

Author: Romain Guieze, Loic Ysebaert, Damien Roos-Weil, Luc-Matthieu Fornecker, Emmanuelle Ferrant, Lysiane Molina, Thérèse Aurran-Schleinitz, Aline Clavert, Sophie de Guibert, Anne-Sophie Michallet, Alain Saad, Bernard Drenou, Philippe Quittet, Benedicte Hivert, Kamel Laribi, Julie Gay, Julien Broséus, Valérie Rouille, David Schwartz, Bruno Pereira, Alain Delmer, and Pierre Feugier
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Published: 2022
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18. High-risk stage IIB Hodgkin lymphoma treated in the H10 and AHL2011 trials: total metabolic tumor volume is a useful risk factor to stratify patients at baseline

Author: Cédric Rossi, Marc André, Jehan Dupuis, Franck Morschhauser, Bertrand Joly, Julien Lazarovici, Hervé Ghesquières, Aspasia Stamatoullas, Emmanuelle Nicolas-Virelizier, Pierre Feugier, Anne-Claire Gac, Hannah Moatti, Luc-Matthieu Fornecker, Bénédicte Deau, Clémentine Joubert, Catherine Fortpied, John Raemaekers, Massimo Federico, Salim Kanoun, Michel Meignan, Alexandra Traverse-Glehen, Anne-Ségolène Cottereau, and René-Olivier Casasnova
Subjects: Dacarbazine, Bleomycin, Clinical Trials, Phase III as Topic, Doxorubicin, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, Humans, Hematology, Prognosis, Vinblastine, Hodgkin Disease, Tumor Burden, Randomized Controlled Trials as Topic
Abstract: Stage IIB Hodgkin lymphoma (HL) patients, with a mediastinum-to-thorax (M/T) ratio of ≥0.33 or extranodal localization have a poor prognosis and are treated either as limited or advanced stage. We compared these two approaches in patients included in two randomized phase III trials enrolling previously untreated early (H10) or advanced stage HL (AHL2011). We included HL patients with Ann-Arbor stage IIB with M/T ≥0.33 or extranodal involvement enrolled in the H10 or AHL2011 trials with available positron emission tomography at baseline (PET0) and after two cycles of chemotherapy (PET2). Baseline total metabolic tumor volume (TMTV) was calculated using the 41% SUVmax method. PET2 response assessment used the Deauville score. One hundred and fourty-eight patients were eligible, including 83 enrolled in the AHL2011 trial and 65 in the H10 trial. The median TMTV value was 155.5 mL (range, 8.3-782.9 mL), 165.6 mL in AHL2011 and 147 mL in H10. PET2 positivity rates were 16.9% (n=14) and 9.2% (n=6) in AHL2011 and H10 patients, respectively. With a median follow-up of 4.1 years (95% confidence interval [CI]: 3.9-4.4), overall 4-year PFS was 88.0%, 87.0% in AHL2011 and 89.2% in H10. In univariate and mutivariate analyses, baseline TMTV and PET2 response influenced significantly progression-free survival (hazard ratio [HR]=4.94, HR=3.49 respectively). Notably, among the 16 patients who relapsed, 13 (81%) had a baseline TMTV baseline ≥155 mL. Upfront ABVD plus radiation therapy or upfront escBEACOPP without radiotherapy provide similar patient’s outcome in high-risk stage IIB HL. TMTV is useful to stratify these patients at baseline.
Published: 2022

19. Comparative analysis of rituximab or obinutuzumab combined with CHOP in first-line treatment of follicular lymphoma

Author: Gwladys Claustre, Coralie Boulanger, Frédéric Maloisel, Nelly Etienne-Selloum, Luc-Matthieu Fornecker, Eric Durot, Florian Slimano, and Véronique Graff
Subjects: Cancer Research, Oncology, General Medicine
Abstract: Rituximab (R) or obinutuzumab (G) combined with CHOP chemotherapy are used in previously untreated follicular lymphoma (FL). The aim is to compare in real life setting the efficacy and safety of these therapeutic strategies and assess the economic impact of introducing G.This retrospective study, performed in 3 centers, included data from all patients who received R-CHOP or G-CHOP for previous untreated FL from June 1st, 2016 to December 31st, 2020. Progression-Free Survival (PFS) were estimated according to the Kaplan-Meier method. A budgetary impact model was performed from the French health care system's perspective.N = 124 patients were included (58 G-CHOP; 66 R-CHOP). Fifty-one and 57 patients achieved a complete response at the end of induction in the G-CHOP and R-CHOP group, respectively. PFS was not significantly longer in the G-CHOP group (HR 0.28; 95% CI 0.08-0.97; p value = 0.14). Hematological toxicity occurred more frequently with G-CHOP than R-CHOP during induction treatment (n = 58; 100% vs. n = 61; 92%), including higher severe neutropenia (grade ≥ 3) (n = 26; 45% vs. n = 23; 35%). Infusion-related reactions during the first infusion occurred more frequently with G-CHOP (n = 19; 33% vs. n = 16; 24%). The introduction of a completed G treatment (induction and maintenance) results in an additional cumulative cost per patient estimated at more than €30,000.Similar results were found in the GALLIUM subgroup analysis study, suggesting that at this time there is no absolute benefit to administer G-CHOP instead of R-CHOP in all patients with previously untreated FL and may encourage clinical and economic trials including quality of life data.
Published: 2021

20. Bendamustine-EAM versus R-BEAM after high-dose cytarabine-based induction in newly diagnosed patients with mantle cell lymphoma, a LYSA retrospective study

Author: Domitille Costes-Tertrais, Thomas Hueso, Thomas Gastinne, Catherine Thieblemont, Lucie Oberic, Krimo Bouabdallah, Sylvain Garciaz, Emmanuelle Tchernonog, Caroline Dartigeas, Vincent Ribrag, Patrick Fogarty, René-Olivier Casasnovas, Roch Houot, Caroline Delette, Sandra Malak, Luc-Matthieu Fornecker, Remy Gressin, Gandhi Damaj, Steven Le Gouill, Centre hospitalier universitaire de Nantes (CHU Nantes), Université Sorbonne Paris Nord, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Paris 5 (UPD5), Hopital Saint-Louis [AP-HP] (AP-HP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital Lapeyronie [Montpellier] (CHU), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], The Lymphoma Academic Research Organisation [Lyon] (LYSARC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Amiens-Picardie, Hôpital René HUGUENIN (Saint-Cloud), CHU Strasbourg, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Adult, Transplantation, [SDV]Life Sciences [q-bio], Cytarabine, Hematopoietic Stem Cell Transplantation, Hematology, Lymphoma, Mantle-Cell, Carmustine, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols, Bendamustine Hydrochloride, Humans, Melphalan, Etoposide, Retrospective Studies
Abstract: International audience; Cytarabine-based immuno-chemotherapy followed by autologous stem cell transplantation (ASCT) consolidation is standard of care for fit patients with Mantle Cell Lymphoma (MCL). BEAM (Carmustine, Etoposide, Aracytine, Melphalan) is among the most frequently used conditioning regimen. Studies comparing BEAM with Bendamustine-EAM (BeEAM) have suggested that patients treated with BeEAM have a better progression-free survival (PFS). We performed a cross-study analysis to better evaluate BeEAM. Thirty-five patients from a retrospective study who received R-DHAP/BeEAM were compared to 245 patients from the LyMa trial (NCT00921414) who all received R-DHAP followed by R-BEAM. PFS and Overall Survival (OS) were estimated using Kaplan-Meier methods. At 2 years there was no difference between R-BEAM and BeEAM in either PFS (84.9% versus 87.9%; p = 0.95) or OS (91.8% versus 94.2%; p = 0.30). Analyses were repeated on a propensity score to reduce biases. Each patient from the BeEAM cohort (n = 30) was matched to three patients from the R-BEAM cohort (n = 90) for age, sex, MIPI score, pre-transplant status disease and rituximab maintenance (RM). PFS and OS at 2 years remained similar between R-BEAM and BeEAM with more renal toxicity in BeEAM group. MCL patients who received R-DHAP induction before ASCT have similar outcome after R-BEAM or BeEAM conditioning regimen.
Published: 2021
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21. Efficacy of Serotherapy on an N501Y Variant of SARS-CoV-2 in a Patient With Chronic Lymphocytic Leukemia

Author: Catherine Humbrecht, Lauriane Eberst, Luc-Matthieu Fornecker, and Colin Vercueil
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Chronic lymphocytic leukemia, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Case Report, Hematology, medicine.disease, Virology, Medicine, Diseases of the blood and blood-forming organs, RC633-647.5, business
Published: 2021
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22. Factors associated with coinfections in invasive aspergillosis: a retrospective cohort study

Author: François Danion, Céline Duval, François Séverac, Philippe Bachellier, Ermanno Candolfi, Vincent Castelain, Raphaël Clere-Jehl, Julie Denis, Laurence Dillenseger, Eric Epailly, Justine Gantzer, Blandine Guffroy, Yves Hansmann, Jean-Etienne Herbrecht, Valérie Letscher-Bru, Pierre Leyendecker, Pauline Le Van Quyen, Pierre-Olivier Ludes, Guillaume Morel, Bruno Moulin, Catherine Paillard, Benjamin Renaud-Picard, Anne-Claude Roche, Marcela Sabou, Francis Schneider, Morgane Solis, Emilie Talagrand-Reboul, Francis Veillon, Marie-Pierre Ledoux, Célestine Simand, Raoul Herbrecht, Pietro Francesco Addeo, Dominique Astruc, Mathieu Baldacini, Karin Bilger, Marie-Pierrette Chenard, Olivier Collange, Tristan Degot, Nadia Dhif, Elise Dicop, Samira Fafi-Kremer, Luc-Matthieu Fornecker, Charline Fuseau, Max Guillot, Mary-Line Harlay, Ralf Janssen-Langenstein, Benoît Jaulhac, Charlotte Kaeuffer, Romain Kessler, Christine Kummerlen, Annegret Laplace, Anne Launoy, Bruno Lioure, Hamid Merdji, Paul-Michel Mertes, Shanti Natarajan-Ame, Gabriel Nisand, Michele Porzio, Julien Pottecher, Maleka Schenck-Dhif, Cécile Sonntag, Elise Toussaint, Anne Zilliox, Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Cancérologie de Strasbourg Europe (ICANS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions Hôte pathogène, Université de Strasbourg (UNISTRA), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Nanomédecine Régénérative (NanoRegMed), Biomatériaux et Bioingénierie (BB), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virulence bactérienne précoce : fonctions cellulaires et contrôle de l'infection aiguë et subaiguë, Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and univOAK, Archive ouverte
Subjects: 0301 basic medicine, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, 030106 microbiology, Coinfections, Computed tomography, Aspergillosis, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Invasive fungal infections, Internal medicine, medicine, Humans, Leukaemia, 030212 general & internal medicine, Mortality, Child, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Aged, Retrospective Studies, Aspergillus species, Aged, 80 and over, medicine.diagnostic_test, business.industry, Coinfection, Hematopoietic Stem Cell Transplantation, Infant, Newborn, Infant, Retrospective cohort study, General Medicine, Middle Aged, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, medicine.disease, 3. Good health, Transplantation, Infectious Diseases, Fungal, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Risk factors, Child, Preschool, Hematologic Neoplasms, business
Abstract: Objectives To describe the coinfections in invasive aspergillosis (IA), to identify factors associated with coinfections, and to evaluate the impact of coinfection on mortality. Patients and methods We conducted a monocentric retrospective study of consecutive putative, probable, or proven IA that occurred between 1997 and 2017. All coinfections, with an onset within 7 days before or after the first sign of aspergillosis, were identified. Factors associated with coinfections and mortality were analysed by multivariable analysis. Results Among the 690 patients with IA included in the study, the median age was 57 years (range 7 days to 90 years). A coinfection was diagnosed in 272/690 patients (39.4%, 95%CI 35.8–43.2). The location of this coinfection was pulmonary only in 131/272 patients (48%), bloodstream only in 66/272 patients (24%) and other/multiple sites in 75/272 patients (28%). Coinfections were bacterial (110/272 patients, 40%), viral (58/272, 21%), fungal (57/272, 21%), parasitic (5/272, 2%) or due to multiple types of pathogens (42/272, 15%). Factors associated with a coinfection in adjusted analysis were: allogeneic haematopoietic stem-cell transplantation (OR 2.3 (1.2–4.4)), other haematological malignancies (OR 2.1 (1.2–3.8)), other underlying diseases (OR 4.3 (1.4–13.6)), lymphopenia (OR 1.7 (1.1-2.5)), C-reactive protein >180 mg/L (OR 1.9 (1.2–3.0)), fever (OR 2.4 (1.5–4.1)), tracheal intubation (OR 2.6 (1.5–4.7)), isolation of two or more different Aspergillus species (OR 2.7 (1.1–6.3)), and the presence of non-nodular lesions on chest computed tomography (OR 2.2 (1.3–3.7) and OR 2.2 (1.2–4.0)). Coinfections were independently associated with a higher mortality at week 12 (adjusted HR 1.5 (1.1–1.9), p Conclusions Coinfections are frequent in IA patients and are associated with higher mortality.
Published: 2021
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23. Intensive chemotherapy followed by autologous stem cell transplantation in primary central nervous system lymphomas (PCNSLs). Therapeutic outcomes in real life-experience of the French Network

Author: Laurence, Schenone, Caroline, Houillier, Marie Laure, Tanguy, Sylvain, Choquet, Kossi, Agbetiafa, Hervé, Ghesquières, Gandhi, Damaj, Anna, Schmitt, Krimo, Bouabdallah, Guido, Ahle, Remy, Gressin, Jérôme, Cornillon, Roch, Houot, Jean-Pierre, Marolleau, Luc-Matthieu, Fornecker, Olivier, Chinot, Frédéric, Peyrade, Reda, Bouabdallah, Cécile, Moluçon-Chabrot, Emmanuel, Gyan, Adrien, Chauchet, Olivier, Casasnovas, Lucie, Oberic, Vincent, Delwail, Julie, Abraham, Virginie, Roland, Agathe, Waultier-Rascalou, Lise, Willems, Franck, Morschhauser, Michel, Fabbro, Renata, Ursu, Catherine, Thieblemont, Fabrice, Jardin, Adrian, Tempescul, Denis, Malaise, Valérie, Touitou, Lucia, Nichelli, Magali, Le Garff-Tavernier, Aurélie, Plessier, Philippe, Bourget, Caroline, Bonmati, Sophie, Wantz-Mézières, Quentin, Giordan, Véronique, Dorvaux, Cyril, Charron, Waliyde, Jabeur, Khê, Hoang-Xuan, Luc, Taillandier, Carole, Soussain, and Thomas, Gastinne
Subjects: Central Nervous System, Lymphoma, Hematopoietic Stem Cell Transplantation, Carmustine, Transplantation, Autologous, Central Nervous System Neoplasms, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols, Humans, Prospective Studies, Neoplasm Recurrence, Local, Busulfan, Cyclophosphamide, Thiotepa, Etoposide
Abstract: We analysed the therapeutic outcomes of all consecutive patients with primary central nervous system lymphoma (PCNSL) registered in the prospective French database for PCNSL and treated with intensive chemotherapy (IC) followed by autologous stem cell transplantation (IC-ASCT) between 2011 and November 2019 (271 patients recruited, 266 analysed). In addition, treatment-related complications of thiotepa-based IC-ASCT were analysed from the source files of 85 patients from 3 centers. Patients had received IC-ASCT either in first-line treatment (n = 147) or at relapse (n = 119). The median age at IC-ASCT was 57 years (range: 22-74). IC consisted of thiotepa-BCNU (n = 64), thiotepa-busulfan (n = 24), BCNU-etoposide-cytarabine-melphalan (BEAM, n = 36) and thiotepa-busulfan-cyclophosphamide (n = 142). In multivariate analysis, BEAM and ASCT beyond the first relapse were adverse prognostic factors for relapse risk. The risk of treatment-related mortality was higher for ASCT performed beyond the first relapse and seemed higher for thiotepa-busulfan-cyclophosphamide. Thiotepa-BCNU tends to result in a higher relapse rate than thiotepa-busulfan-cyclophosphamide and thiotepa-busulfan. This study confirms the role of IC-ASCT in first-line treatment and at first-relapse PCNSL (5-year overall survival rates of 80 and 50%, respectively). The benefit/risk ratio of thiotepa-busulfan/thiotepa-busulfan-cyclophosphamide-ASCT could be improved by considering ASCT earlier in the course of the disease and dose adjustment of the IC.
Published: 2021

24. Outcomes of refractory or relapsed Hodgkin lymphoma patients with post-autologous stem cell transplantation brentuximab vedotin maintenance: a French multicenter observational cohort study

Author: Amira Marouf, Anne Segolene Cottereau, Salim Kanoun, Paul Deschamps, Michel Meignan, Patricia Franchi, David Sibon, Clara Antoine, Thomas Gastinne, Cecile Borel, Mohammad Hammoud, Guillaume Sicard, Romane Gille, Doriane Cavalieri, Aspasia Stamatoullas, Lauriane Filliatre-Clement, Julien Lazarovici, Adrien Chauchet, Luc-Matthieu Fornecker, Sandy Amorin, Mathieu Rocquet, Nicole Raus, Barbara Burroni, Marie Therese Rubio, Didier Bouscary, Philippe Quittet, Rene Olivier Casasnovas, Pauline Brice, Herve Ghesquieres, Jérôme Tamburini, Benedicte Deau, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Lymphoma Academic Research Organisation [Lyon] (LYSARC), National Cystic Fibrosis Reference Center [CHU Necker] (CNR - INSERM U1151), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor [Créteil], Aix Marseille Université (AMU), Centre Léon Bérard [Lyon], CHU Clermont-Ferrand, Service d'hématologie [CRLCC Henri Becquerel], Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Clinique Louis-Pasteur, Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], Service d'Hématologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Hôpital Saint Vincent de Paul de Lille, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), 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 des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Montpellier (UM), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de Genève = University of Geneva (UNIGE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Henri Mondor, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), and Université de Genève (UNIGE)
Subjects: Brentuximab Vedotin, Salvage Therapy, Immunoconjugates, [SDV]Life Sciences [q-bio], Hematopoietic Stem Cell Transplantation, Humans, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematology, Hodgkin Disease, Transplantation, Autologous, ComputingMilieux_MISCELLANEOUS, Stem Cell Transplantation
Abstract: International audience; Not available.
Published: 2021
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25. Sinusoidal obstruction syndrome: a warning about autologous stem cell transplantation preceded by regimens containing oxaliplatin

Author: Frédérique Kuhnowski, Jean Philippe Richardet, Marie-Pierre Moles, Sébastien Mulé, Sylvie Glaisner, Manel Bedoui, Jehane Fadlallah, Julien Calderaro, Luc-Matthieu Fornecker, Pierre-Edouard Debureaux, Daniel Azoulay, Delphine Le Febvre de Nailly, Jerome Tamburini, Jehan Dupuis, Emmanuelle Tavernier, Corinne Haioun, David Sibon, and Vincent Camus
Subjects: Transplantation, medicine.medical_specialty, business.industry, Hematopoietic Stem Cell Transplantation, Hepatic Veno-Occlusive Disease, Hematology, Transplantation, Autologous, Oxaliplatin, Surgery, Autologous stem-cell transplantation, medicine, Humans, business, medicine.drug
Published: 2020
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26. Intravenous high-dose methotrexate based systemic therapy in the treatment of isolated primary vitreoretinal lymphoma: an LOC network study

Author: Gandhi Damaj, Khê Hoang-Xuan, Emmanuel Gyan, Marion Lam, Laurent Meyer, Magali Sampo, Anna Schmitt, Sylvain Choquet, Cécile Moluçon-Chabrot, Remy Gressin, Caroline Houillier, Adrien Chauchet, Jérôme Tamburini-Bonnefoy, Laurent Kodjikian, Marie-Laure Le Lez, Lucie Oberic, Roch Houot, Christelle Schneider, Sarra Gattoussi, Hélène Massé, Béatrice Cochener, Jean-Claude Quintyn, Nathalie Cassoux, Priscille Ollé, Karine Angioi-Duprez, Luc-Matthieu Fornecker, Carole Soussain, Jean-Pierre Marolleau, Guido Ahle, Marie-Pierre Moles, Christophe Chiquet, Claire Schwartz, Marie Blonski, Fabien Croisé, Valérie Touitou, Laurent Ballonzoli, Frédéric Mouriaux, Hervé Ghesquières, Bahram Bodaghi, Adrian Tempescul, Magali Le Garff-Tavernier, Emeline Tabouret, Eve Rousseau, Paul Franciane, Benjamin Jany, Antoine P. Brézin, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Institut Curie [Paris], Université de Paris (UP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Institut Bergonié [Bordeaux], UNICANCER, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU de Bordeaux Pellegrin [Bordeaux], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ophtalmologie [Hôpital de la Timone - APMH], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital pasteur [Colmar], CHU Grenoble, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Clermont-Ferrand, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Strasbourg, Institut de neurosciences translationnelles de Paris (NeurATRIS - IHU-A-ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), None, Université Paris Cité (UPCité), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Chard-Hutchinson, Xavier, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, medicine.medical_specialty, Antimetabolites, Antineoplastic, medicine.medical_treatment, Retinal Neoplasms, [SDV]Life Sciences [q-bio], Population, Disease, Systemic therapy, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Intraocular Lymphoma, Internal medicine, medicine, Humans, education, Aged, Aged, 80 and over, Chemotherapy, education.field_of_study, business.industry, Hematology, Middle Aged, Prognosis, High dose methotrexate, 3. Good health, [SDV] Life Sciences [q-bio], Methotrexate, Treatment Outcome, 030220 oncology & carcinogenesis, Toxicity, 030221 ophthalmology & optometry, Administration, Intravenous, Female, business, medicine.drug, Vitreoretinal lymphoma
Abstract: International audience; The treatment of primary vitreoretinal lymphoma (PVRL) remains controversial regarding the use of local, systemic, or combined treatments. The aim of this study was to analyze the efficacy and toxicity of intravenous high-dose methotrexate (IV HD-MTX) based systemic therapy in a uniformly treated population of PVRL patients. From a nationwide French database, we retrospectively selected 59 patients (median age: 70 years, median Karnofsky Performance Status: 90%) with isolated PVRL at diagnosis who received first-line treatment with HD-MTX between 2011-2018. 8/59 patients also received a local treatment. No deaths or premature discontinuations of MTX due to toxicity were reported. A complete response was obtained in 40/57 patients after chemotherapy. Before treatment, IL-10 was elevated in the aqueous humor (AH) or in the vitreous in 89% of patients. After treatment, AH IL-10 was undetectable in 87% of patients with a CR/uCR/PR and detectable in 92% of patients with PD/SD. After a median follow-up of 61 months, 41/59 (69%) patients had relapsed, including 29 isolated ocular relapses as the first relapse and a total of 22 brain relapses. The median overall survival, progression-free survival, ocular-free survival and brain-free survival were 75, 18, 29 and 73 months, respectively. IV HD-MTX based systemic therapy as a first-line treatment for isolated PVRL is feasible, with acceptable toxicity, even in an elderly population. This strategy seems efficient to prevent brain relapse with prolonged overall survival. However, the ocular relapse rate remains high. New approaches are needed to improve local control of this disease, and ocular assessment could be completed by monitoring AH IL-10.
Published: 2021
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27. The landscape of copy number variations in classical Hodgkin lymphoma: a joint KU Leuven and LYSA study on cell-free DNA

Author: Joris Vermeesch, Anne-Claire Gac, Iwona Wlodarska, Luc Dehaspe, Marc André, Peter Vandenberghe, Christophe Bonnet, Julien Lazarovici, Lieselot Buedts, Thomas Tousseyn, Luc-Matthieu Fornecker, Daan Dierickx, Lukas Marcelis, Rene-Olivier Casasnovas, Christiane Copie-Bergman, Julio Finalet-Ferreiro, Bettina Fabiani, Kamal Bouabdallah, Olivier Gheysens, UCL - (MGD) Service d'hématologie, and UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie
Subjects: Male, Oncology, medicine.medical_specialty, Lymphoid Neoplasia, DNA Copy Number Variations, Somatic cell, Hematology, Metabolic tumor volume, Biology, medicine.disease, Hodgkin Disease, Lymphoma, medicine.anatomical_structure, Cell-free fetal DNA, Reed–Sternberg cell, Internal medicine, Classical Hodgkin lymphoma, medicine, Humans, Copy-number variation, Neoplasm Recurrence, Local, Reed-Sternberg Cells, Cell-Free Nucleic Acids, Lymph node
Abstract: The low abundance of Hodgkin/Reed-Sternberg (HRS) cells in lymph node biopsies in classical Hodgkin lymphoma (cHL) complicates the analysis of somatic genetic alterations in HRS cells. As circulating cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA) from HRS cells, we prospectively collected cfDNA from 177 patients with newly diagnosed, mostly early-stage cHL in a monocentric study at Leuven, Belgium (n = 59) and the multicentric BREACH study by Lymphoma Study Association (n = 118). To catalog the patterns and frequencies of genomic copy number aberrations (CNAs), cfDNA was sequenced at low coverage (0.26×), and data were analyzed with ichorCNA to yield read depth-based copy number profiles and estimated clonal fractions in cfDNA. At diagnosis, the cfDNA concentration, estimated clonal fraction, and ctDNA concentration were significantly higher in cHL cases than controls. More than 90% of patients exhibited CNAs in cfDNA. The most frequent gains encompassed 2p16 (69%), 5p14 (50%), 12q13 (50%), 9p24 (50%), 5q (44%), 17q (43%), 2q (41%). Losses mostly affected 13q (57%), 6q25-q27 (55%), 4q35 (50%), 11q23 (44%), 8p21 (43%). In addition, we identified loss of 3p13-p26 and of 12q21-q24 and gain of 15q21-q26 as novel recurrent CNAs in cHL. At diagnosis, ctDNA concentration was associated with advanced disease, male sex, extensive nodal disease, elevated erythrocyte sedimentation rate, metabolic tumor volume, and HRS cell burden. CNAs and ctDNA rapidly diminished upon treatment initiation, and persistence of CNAs was associated with increased probability of relapse. This study endorses the development of ctDNA as gateway to the HRS genome and substrate for early disease response evaluation. ispartof: BLOOD ADVANCES vol:5 issue:7 pages:1991-2002 ispartof: location:United States status: published
Published: 2021

28. Rituximab-Lenalidomide-Ibrutinib Combination for Relapsed/Refractory Primary CNS Lymphoma: A Case Series of the LOC Network

Author: Luc-Matthieu Fornecker, Cécile Chabrot, Marie-Pierre Moles-Moreau, Guido Ahle, Lise Willems, Agathe Waultier-Rascalou, Caroline Houillier, Khê Hoang-Xuan, and Carole Soussain
Subjects: Oncology, Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Central Nervous System Neoplasms, chemistry.chemical_compound, Autologous stem-cell transplantation, Refractory, Piperidines, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Lenalidomide, Aged, Retrospective Studies, Chemotherapy, Series (stratigraphy), business.industry, Adenine, Middle Aged, chemistry, Ibrutinib, Toxicity, Rituximab, Female, Neurology (clinical), Lymphoma, Large B-Cell, Diffuse, Neoplasm Recurrence, Local, business, medicine.drug
Abstract: Background and ObjectivesTo evaluate the efficacy and tolerance of the association rituximab-lenalidomide-ibrutinib (R2I) in relapsed/refractory (R/R) primary CNS lymphoma (PCNSL).MethodsR/R PCNSL patients treated with R2I were retrospectively selected and analyzed from the French LOC database.ResultsFourteen patients (median age: 63 years, median Karnofsky Performance Status: 75%) received R2I, administered after a median of 2 previous lines of chemotherapy, including autologous stem cell transplantation (ASCT) in 5 cases. The best response was complete response in 4/14 patients and partial response in 4/14 patients, achieved in a median of 2.5 months. Three responder patients received consolidation treatment (WBRT: N = 2, ASCT: N = 1) after R2I, and R2I served as a bridge before CAR-T cell therapy for one patient. R2I was discontinued due to toxicity in 3/14 patients. There were no toxicity-related deaths.DiscussionThe R2I combination resulted in a high rate of response of rapid-onset in heavily pretreated patients with poor prognosis, with manageable toxicity, and allowed 3 patients to proceed to consolidation. Although preliminary, these results support the use of R2I for R/R PCNSL failing conventional chemotherapies.Classification of EvidenceThis study provides Class IV evidence that combination of rituximab-lenalidomide-ibrutinib induces a high rate of response in heavily pretreated R/R PCNSL.
Published: 2021

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

Author: Roch Houot, Emmanuelle Nicolas Virelizier, Jehan Dupuis, Magda Alexis, Virginie De Wilde, Luc-Matthieu Fornecker, Julien Lazarovici, Marc André, Franck Morschhauser, David Sibon, Judith Racapé, Hervé Ghesquières, Anne-Claire Gac, Delphine Pranger, Hannah Moatti, Isabelle Demeestere, Hervé Maisonneuve, Julie Dechene, Adrian Tempescul, René-Olivier Casasnovas, Mohamed Touati, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - (MGD) Service d'hématologie
Subjects: Oncology, Adult, Anti-Mullerian Hormone, Male, Cancer Research, medicine.medical_specialty, endocrine system, Dacarbazine, Bleomycin, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Testis, medicine, Humans, Doxorubicin, In patient, Prospective Studies, Etoposide, 030219 obstetrics & reproductive medicine, business.industry, Ovary, Recovery of Function, Hodgkin Disease, Vinblastine, Regimen, chemistry, ABVD, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Female, business, medicine.drug
Abstract: PURPOSE The prospective, randomized AHL2011 trial demonstrated that the use of the doxorubicin, bleomycin, vinblastine, and dacarbazine regimen (ABVD) after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) in early responders on the basis of a positron emission tomography (PET)–driven strategy was safe and minimized toxicity compared with standard 6 BEACOPPescalated cycles. This substudy investigated the benefit of this strategy in gonadal function and fertility in patients under 45 years old. METHODS Ovarian function was assessed by serum measurement of follicle-stimulating hormone (FSH), estradiol, and anti-müllerian hormone in women, and semen analysis, FSH, and testosterone levels were used to evaluate testicular function in men at baseline, end of treatment, and during 5 years of follow-up. RESULTS A total of 145 women and 424 men, enrolled between May 19, 2011, and April 29, 2014, were included. The risk of premature ovarian insufficiency (FSH > 24 IU/L) and of having a low ovarian reserve (anti-müllerian hormone < 0.5 ng/mL) was reduced after treatment in the PET-driven group (odds ratio [OR], 0.20; 95% CI, 0.08 to 0.50; P = .001 and OR, 0.15; 95% CI, 0.04 to 0.56, P = .005, respectively). Both parameters were correlated with age and dose of alkylating agents. However, no significant differences were observed in terms of pregnancy rates. Men in the PET-driven group had a higher recovery rate of sperm parameters after treatment compared with the standard BEACOPPescalated group, as well as a lower risk of severe testicular damage (OR, 0.26; 95% CI, 0.13 to 0.5; P < .0001) and a higher likelihood of achieving pregnancy (OR, 3.7; 95% CI, 1.4 to 9.3; P = .004). CONCLUSION Although both treatments affected ovarian reserve and spermatogenesis, the PET-driven strategy decreased the risk of gonadal dysfunction and infertility in advanced Hodgkin lymphoma.
Published: 2021

30. Additional file 1 of A French multicentric prospective prognostic cohort with epidemiological, clinical, biological and treatment information to improve knowledge on lymphoma patients: study protocol of the 'REal world dAta in LYmphoma and survival in adults' (REALYSA) cohort

Author: Ghesquières, Hervé, Rossi, Cédric, Cherblanc, Fanny, Guyader-Peyrou, Sandra Le, Fontanet Bijou, Sujobert, Pierre, Fabbro-Peray, Pascale, Bernier, Adeline, Belot, Aurélien, Loic Chartier, Luc-Matthieu Fornecker, Baldi, Isabelle, Krimo Bouabdallah, Laurent, Camille, Oberic, Lucie, Morineau, Nadine, Gouill, Steven Le, Morschhauser, Franck, Haioun, Corinne, Gandhi Damaj, Guidez, Stéphanie, Labouré, Gaëlle, Fitoussi, Olivier, Lebras, Laure, Gressin, Rémy, Salles, Gilles, Ysebaert, Loïc, and Monnereau, Alain
Subjects: immune system diseases, hemic and lymphatic diseases
Abstract: Additional file 1. Lymphoma subtypes included and excluded in the study, according to the 2016 WHO classification. Detailed list of lymphoma subtypes included and excluded of the study.
Published: 2021
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31. Comparison of Short- and Long-Term Mortality in Patients with or without Cancer Admitted to the ICU for Septic Shock: A Retrospective Observational Study

Author: Pierrick Le Borgne, Léa Feuillassier, Maleka Schenck, Jean-Etienne Herbrecht, Ralf Janssen-Langenstein, Celestine Simand, Justine Gantzer, Simon Nannini, Luc-Matthieu Fornecker, Karine Alamé, François Lefebvre, Vincent Castelain, Francis Schneider, Raphaël Clere-Jehl, Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital de Hautepierre [Strasbourg], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Cancérologie de Strasbourg Europe (ICANS), Immuno-Rhumatologie Moléculaire, and univOAK, Archive ouverte
Subjects: critical care, Cancer Research, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, septic shock, neoplasms, immunocompromised host, treatment outcome, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sciences du Vivant [q-bio]/Cancer
Abstract: Introduction: Cancer patients are at high risk of developing septic shock (SSh) and are increasingly admitted to ICU given their improved long-term prognosis. We, therefore, compared the prognosis of cancer and non-cancer patients with SSh. Methods: We conducted a monocentric, retrospective cohort study (2013-2019) on patients admitted to ICU for SSh. We compared the clinical characteristics and management and studied short- and long-term mortality with ICU and in-hospital mortality and 1-year survival according to cancer status. Results: We analyzed 239 ICU stays in 210 patients, 59.5% of whom were men (n = 125), with a median age of 66.5 (IQR 56.3-77.0). Of the 121 cancer patients (57.6% of all patients), 70 had solid tumors (33.3%), and 51 had hematological malignancies (24.3%). When comparing ICU stays of patients with versus without cancer (n = 148 vs. n = 91 stays, respectively), mortality reached 30.4% (n = 45) vs. 30.0% (n = 27) in the ICU (p = 0.95), and 41.6% (n = 59) vs. 35.6% (n = 32) in hospital (p = 0.36), respectively. ICU length of stay (LOS) was 5.0 (2.0-11.3) vs. 6.0 (3.0-15.0) days (p = 0.27), whereas in-hospital LOS was 25.5 (13.8-42.0) vs. 19.5 (10.8-41.0) days (p = 0.33). Upon multivariate analysis, renal replacement therapy (OR = 2.29, CI95%: 1.06-4.93, p = 0.03), disseminated intravascular coagulation (OR = 5.89, CI95%: 2.49-13.92, p < 0.01), and mechanical ventilation (OR = 7.85, CI95%: 2.90-21.20, p < 0.01) were associated with ICU mortality, whereas malignancy, hematological, or solid tumors were not (OR = 1.41, CI95%: 0.65-3.04; p = 0.38). Similarly, overall cancer status was not associated with in-hospital mortality (OR = 1.99, CI95%: 0.98-4.03, p = 0.06); however, solid cancers were associated with increased in-hospital mortality (OR = 2.52, CI95%: 1.12-5.67, p = 0.03). Lastly, mortality was not significantly different at 365-day follow-up between patients with and without cancer. Conclusions: In-hospital and ICU mortality, as well as LOS, were not different in SSh patients with and without cancer, suggesting that malignancies should no longer be considered a barrier to ICU admission. Keywords: critical care; immunocompromised host; neoplasms; septic shock; treatment outcome.
Published: 2022
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32. Caractérisation du profil protéomique du Syndrome de Richter

Author: Romain Piucco, Romain Morizot, Luc-Matthieu Fornecker, Pierre Feugier, Sébastien Hergalant, Julien Broséus, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Strasbourg, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Proteomics, Protéome, Diffuse Large B-cell Lymphoma, Syndrome de Richter, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Leucémie Lymphoïde Chronique, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Chronic Lymphocytic Leukemia, Lymphome B Diffus à Grandes Cellules, Richter syndrome, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: National audience; Le Syndrome de Richter (SR) correspond au développement d’un lymphome secondaire agressif chez les patients présentant une Leucémie Lymphoïde Chronique (LLC). Il possède un phénotype Lymphome B Diffus à Grandes Cellules (LBDGC) dans 90-95 % des cas et se caractérise par une morphologie semblable aux LBDGC primaires avec un phénotype immunohistochimique non-GC dans 90 % des cas. Du fait de sa complexité et de sa chimiorésistance, le pronostic du SR reste sombre. Le protéome est constitué par l’ensemble des protéines. C’est une unité complexe et dynamique qui va varier en fonction des conditions biologiques. Les analyses du domaine protéomique se sont popularisées ces dernières années avec le développement de la spectrométrie de masse en tandem (SDM MS/MS) permettant l’acquisition d’un jeu de données conséquent mais impliquant une multitude de biais (grande hétérogénéité, valeurs manquantes, seuils de détection) à intégrer dans les analyses, avec l’aide de la bioinformatique.Pour la première fois, une étude protéomique a été réalisée par SDM couplée à la chromatographie en phase liquide (LC-MS/MS) en stratégie « bottom-up » de tumeurs ganglionnaires de 21 patients atteints du SR, 9 atteints de Lymphomes B Diffus à Grandes Cellules (LBDGC) primaires chimioréfractaires, 19 LBDGC primaires chimiosensibles et 10 LBDGC secondaires hors SR. Un protocole bioinformatique permettant une reconstruction efficace et une analyse statistique du protéome tant au niveau peptidique que protéique a été mis en place. Cette approche a permis la quantification fine de 1772 protéines et 11385 peptides dans les 59 échantillons. Les analyses statistiques ont mis en lumière 206 protéines et 1437 peptides (correspondant à 271 protéines) différentielles (FDR < 0,05) dans le SR comparativement aux autres LBDGC. L’exploration de ces données a permis de mettre en évidence des protéines impliquées dans la signalisation liée au B-Cell Receptor (BCR), à la mort cellulaire, la matrice extracellulaire et l’inflammation. L’existence de deux profils protéomiques du SR différents est également décrite.Cette étude contribue ainsi à une meilleure compréhension des mécanismes physiopathologiques du SR, permettant l’ouverture de potentielles nouvelles voies thérapeutiques tout en apportant de nouvelles données distinguant le SR des LBDGC primitifs chimioréfractaires et des LBDGC secondaires.
Published: 2020

33. Bendamustine-EAM versus BEAM regimen in patients with mantle cell lymphoma undergoing autologous stem cell transplantation in the frontline setting: a multicenter retrospective study from Lymphoma Study Association (LYSA) centers

Author: Olivier Tournilhac, Krimo Bouabdallah, Sylvain Garciaz, Reda Bouabdallah, Remy Gressin, Frederic Peyrade, Sandra Malak, Sylvain Chantepie, Steven Le Gouill, Baptiste Delapierre, Rémy Morello, René-Olivier Casasnovas, Thomas Gastinne, Emmanuelle Tchernonog, Luc-Matthieu Fornecker, Gandhi Damaj, Benoit Tessoulin, Julie Abraham, Emmanuel Gyan, Richard Lemal, Caroline Delette, Roch Houot, Ahmad Ibrahim, Cécile Borel, Thomas Hueso, Eric Durot, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Plate-forme CytoCell [Nantes] (CRCINA – Unité Inserm U1232), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-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), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Amiens-Picardie, Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Pontchaillou [Rennes], Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Clermont-Ferrand, Hôpital René HUGUENIN (Saint-Cloud), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Toulouse School of Economics (TSE), Université Toulouse 1 Capitole (UT1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Strasbourg, Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Centre Antoine Lacassagne de Nice, CHU Grenoble, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Makassed General Hospital [Beirut, Lebanon], Plateforme CYTOCELL Nantes (CRCINA-CYTOCELL), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Toulouse School of Economics (TSE-R), Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Adult, Melphalan, Bendamustine, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Lymphoma, Mantle-Cell, Transplantation, Autologous, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Bendamustine Hydrochloride, Humans, Medicine, Prospective Studies, Etoposide, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Transplantation, Carmustine, business.industry, Cytarabine, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, 3. Good health, Regimen, 030220 oncology & carcinogenesis, Mantle cell lymphoma, business, 030215 immunology, medicine.drug
Abstract: The combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) as conditioning regimen prior to autologous stem-cell transplantation (ASCT) remains the standard of care for patients with mantle cell lymphoma (MCL) who are eligible for transplantation. The replacement of carmustine with bendamustine (BeEAM) was described as a promising alternative in non-Hodgkin lymphoma. The aim of this retrospective study was to compare the BeEAM with the BEAM regimen in MCL patients in the frontline setting. Sixty and 108 patients were included in the BeEAM and the BEAM groups, respectively. At 3 years, progression-free survival (PFS) was significantly higher in the BeEAM than in the BEAM group (84% [73-96] vs. 63% [51-79], p = 0.03). The overall survival was not statistically different between the two groups (p = 0.2). In multivariable analysis, BeEAM regimen remained associated with higher PFS (HR = 0.377, 95% CI, 0.146-0.970; p = 0.043). Subgroup analyses in patients treated with prior rituximab-aracytine induction alone showed that BeEAM improved the PFS compared with BEAM regimen (p = 0.04). Despite the high rate of acute renal failure KDIGO III (32%), treatment-related mortality was not increased with the BeEAM regimen. A prospective randomized trial will be necessary to confirm the beneficial effect of the BeEAM regimen in MCL patients undergoing ASCT.
Published: 2020
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34. Impact of TP53 mutations in acute myeloid leukemia patients treated with azacitidine

Author: Laetitia Largeaud, Audrey Sarry, Naïs Prade, Bastien Cabarrou, Sarah Bertoli, Eric Delabesse, Julien Plenecassagnes, Célestine Simand, Manon Cassou, Stéphanie Lagarde, Luc-Matthieu Fornecker, Isabelle Luquet, Véronique De Mas, Thomas Filleron, Pierre Bories, and Christian Recher
Subjects: Oncology, Male, endocrine system diseases, Epidemiology, Cancer Treatment, Gene Identification and Analysis, Kaplan-Meier Estimate, Gene mutation, Hematologic Cancers and Related Disorders, 0302 clinical medicine, Medicine and Health Sciences, Prospective Studies, Registries, Frameshift Mutation, Aged, 80 and over, Multidisciplinary, Leukemia, Cancer Risk Factors, Myeloid leukemia, Hematology, Middle Aged, Myeloid Leukemia, Prognosis, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Cohort, Azacitidine, Medicine, Female, France, Karyotypes, medicine.drug, Research Article, Acute Myeloid Leukemia, medicine.medical_specialty, Antimetabolites, Antineoplastic, Science, Decitabine, Frameshift mutation, 03 medical and health sciences, Cytogenetics, Diagnostic Medicine, Internal medicine, medicine, Genetics, Biomarkers, Tumor, Humans, Mutation Detection, neoplasms, Aged, business.industry, Biology and Life Sciences, Cancers and Neoplasms, Genes, p53, Regimen, Medical Risk Factors, Mutation, Tumor Suppressor Protein p53, business, 030215 immunology
Abstract: Hypomethylating agents are a classical frontline low-intensity therapy for older patients with acute myeloid leukemia. Recently, TP53 gene mutations have been described as a potential predictive biomarker of better outcome in patients treated with a ten-day decitabine regimen., However, functional characteristics of TP53 mutant are heterogeneous, as reflected in multiple functional TP53 classifications and their impact in patients treated with azacitidine is less clear. We analyzed the therapeutic course and outcome of 279 patients treated with azacitidine between 2007 and 2016, prospectively enrolled in our regional healthcare network. By screening 224 of them, we detected TP53 mutations in 55 patients (24.6%), including 53 patients (96.4%) harboring high-risk cytogenetics. The identification of any TP53 mutation was associated with worse overall survival but not with response to azacitidine in the whole cohort and in the subgroup of patients with adverse karyotype. Stratification of patients according to three recent validated functional classifications did not allow the identification of TP53 mutated patients who could benefit from azacitidine. Systematic TP53 mutant classification will deserve further exploration in the setting of patients treated with conventional therapy and in the emerging field of therapies targeting TP53 pathway.
Published: 2020

35. Tuberculosis and atypical mycobacterial infections in ruxolitinib-treated patients with primary or secondary myelofibrosis or polycythemia vera

Author: Elise Toussaint, Luc-Matthieu Fornecker, S. Lescuyer, Raoul Herbrecht, Marie-Pierre Ledoux, Laurent Mauvieux, Céline Duval, Simon Gravier, Frédéric Maloisel, and Shanti Natarajan-Amé
Subjects: 0301 basic medicine, Microbiology (medical), Male, medicine.medical_specialty, Ruxolitinib, Polycythaemia, Tuberculosis, 030106 microbiology, Mycobacterium Infections, Nontuberculous, Gastroenterology, lcsh:Infectious and parasitic diseases, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Polycythemia vera, Internal medicine, Secondary Myelofibrosis, Nitriles, medicine, Humans, Mycobacterium avium complex, lcsh:RC109-216, 030212 general & internal medicine, Polycythemia Vera, Protein Kinase Inhibitors, Aged, biology, business.industry, General Medicine, medicine.disease, biology.organism_classification, Infectious Diseases, Pyrimidines, Primary Myelofibrosis, Cohort, Pyrazoles, Female, business, medicine.drug, Mycobacterium avium
Abstract: Ruxolitinib is a JAK-1/JAK-2 inhibitor indicated for the treatment of polycythemia vera and primary or secondary myelofibrosis. Only one patient (0.2%) was diagnosed with tuberculosis among the 485 patients receiving ruxolitinib in the four pivotal trials. Fourteen cases of tuberculosis have since been reported. We observed two (3%) mycobacterial infections (one due to Mycobacterium tuberculosis and one due to Mycobacterium avium complex) in our cohort of 65 patients receiving ruxolitinib. This observation suggests that the rate of mycobacterial infection might be higher than that observed in the pivotal trials and that atypical mycobacterial infections can also occur. Keywords: Ruxolitinib, Mycobacteria, Tuberculosis, Mycobacterium tuberculosis, Mycobacterium avium complex
Published: 2019

36. The Contribution of CD148, CD180 and CD200 Combination in the Diagnosis of Chronic B-Cell Lymphoproliferative Disorders

Author: Alice Eischen, Caroline Mayeur-Rousse, Anne-Cécile Galoisy, Delphine Rolland, Eric Jeandidier, Thibaut Fabacher, Luc-Matthieu Fornecker, Laurent Mauvieux, Carine Gervais, Raoul Herbrecht, Laurent Miguet, and Razvan Bizoi
Subjects: medicine.anatomical_structure, business.industry, Immunology, medicine, Lymphoproliferative disorders, Cell Biology, Hematology, medicine.disease, business, Biochemistry, B cell
Abstract: Introduction: B-cell immunophenotype could be swiftly assessed by flow cytometry on blood samples or bone marrow aspirate specimens. It provides crucial information later refined with histologic, genetic and molecular features to assert accurate diagnosis of chronic B-cell lymphoproliferative disorders (B-CLPD). Besides Matutes score we identified additional useful markers, i.e. CD148 and CD180 to classify mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), respectively. Furthermore, CD200 is known to be highly expressed in chronic lymphoid leukemia (CLL) while absent in MCL. Hypothesis: The determination of CD148, CD180 and CD200 expression on B-cells by flow cytometry on blood samples and/or bone marrow aspirates could be a potent tool to accurately identify B-CLPD. We postulated the existence of the following specific expression patterns in B-CLPD: CD148 dim/CD180 dim/CD200 bright for CLL, CD148 dim/CD180 dim/CD200 dim for lymphoplasmocytic lymphoma (LPL), CD148 bright/CD180 dim/CD200 neg/dim for MCL and CD148 dim/CD180 bright/CD200 dim for MZL . Methods: In a prospective study we investigated the expression of CD148/CD180/CD200 on B-cells from 673 patients at the time of B-CLPD diagnosis in our hospital from 2014 to 2020. We analyzed 440 blood and 233 bone marrow aspirate specimens using a BD FACSCanto II flow cytometry instrument. Based solely on CD148/CD180/CD200 specific expression patterns we postulated a diagnosis of CLL, LPL, MCL or MZL. These postulated diagnoses were later confronted to the final diagnoses when all histologic, genetic and molecular features were finalized. Sensitivity, specificity, positive and negative predictive values of the expression profiles were determined. In addition, to investigate the relative importance of these three CD markers we then normalized their mean fluorescence intensities (MFI) and applied several supervised machine learning algorithms including Logistic Regression, Random Forest and Light Gradient Boosting Machine (LightGBM). Results: Out of the 673 clinical samples the CD148/CD180/CD200 expression patterns classified 212 specimens as CLL/SLL (30.8%), 160 as LPL (23.8%), 76 as MCL (11.28%) and 169 as MZL (25%). These diagnosis hypotheses were retrospectively compared to the final diagnoses based on all histologic, genetic and molecular features These diagnosis hypotheses of CLL, LPL, MCL and MZL were consistent with the final diagnosis in 583 out of the 617 corresponding cases (94%) with high positive and negative predictive values. The characteristics of the diagnosis accuracy are detailed in the table below. HCL and FL were not further investigated as their immunophenotype usually do not overlap with those of other B-CLPD. Seventeen out of 617 patients (17/617, 5.3%) did not displayed a clear CD148/CD180/CD200 pattern: 9 LPL, 4 CLL and 4 MZL. In sixteen patients (16/617, 5.0%) the diagnosis hypothesis based on this strategy was not confirmed after completion of the exploration including karyotype, MYD88 L265P mutational status, CCND1 overexpression and pathology explorations. We next investigated the relative importance of these 3 markers. We focused on MFI values of CD148, CD180 and CD200 and three categorical "positive or negative" markers (CD5, CD23, FMC7) that were assembled into a composite marker. After Cox-box normalization of CD148, CD180 and CD200 MFIs, a set of supervised machine learning algorithms including Logistic Regression, Random Forest and Light Gradient Boosting Machine (LightGBM) were applied to the cohort of CLL, LPL, MCL and MZL. We established that the highest diagnosis weights were obtained for CD200 in CLL, CD200 and CD148 in MCL (negatively and positively, respectively), CD180 in MZL. In LPL, CD148, CD180 and CD200 had the highest weights using LightGBM and Random Forest algorithms, while Logistic Regression determined that CD5 and CD23 had the highest (negative) weights. In conclusion, the determination of CD148/CD180/CD200 surface expression patterns by flow cytometry, along with morphology, allowed to assert an accurate diagnosis hypothesis in CLL, MCL, LPL and MZL with high positive and negative predictive values. Machine learning algorithms allowed to measure the relative importance of these markers, that could be of great help in case of discordant expression of the main diagnosis markers. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
Published: 2021
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37. Deep-Learning Assessed Muscular Hypodensity Independently Predicts Mortality in DLBCL Patients Younger Than 60 Years

Author: Franck Morschhauser, Clément Bailly, Corinne Haioun, Benoit Tessoulin, Hervé Tilly, Vincent Ribrag, Marc André, Steven Le Gouill, Catherine Thieblemont, Bruno Villemagne, Thierry Lamy, Lucie Oberic, René-Olivier Casasnovas, Luc-Matthieu Fornecker, Kamal Bouabdallah, Remy Gressin, Maxime Jullien, Pierre Feugier, Guillaume Cartron, Jean-Marc Schiano de Colella, Olivier Hermine, Hervé Ghesquières, Gandhi Damaj, Christophe Bonnet, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service d'hématologie, Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Lille, Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Institut Gustave Roussy (IGR), Université Paris-Saclay, Département d'hématologie [Gustave Roussy], CHU Pontchaillou [Rennes], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Bordeaux [Bordeaux], Hôpital Henri Mondor, Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Institut de Cancérologie de Strasbourg Europe (ICANS), CHU Strasbourg, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Necker - Enfants Malades [AP-HP], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Liège (CHU-Liège), Université de Liège, CHU UCL Namur, Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Bernardo, Elizabeth
Subjects: Cancer Research, medicine.medical_specialty, diffuse large B-cell lymphoma, convolutional neural network, [SDV.CAN]Life Sciences [q-bio]/Cancer, muscle depletion, Gastroenterology, Article, sarcopenia, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Hounsfield scale, medicine, Progression-free survival, Risk factor, RC254-282, Predictive marker, muscle hypodensity, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Skeletal muscle, medicine.disease, U-NET, medicine.anatomical_structure, Oncology, Sarcopenia, Cohort, business, Diffuse large B-cell lymphoma
Abstract: Background. Muscle depletion (MD) assessed by computed tomography (CT) has been shown to be a predictive marker in solid tumors, but has not been assessed in non-Hodgkin’s lymphomas. Despite software improvements, MD measurement remains highly time-consuming and cannot be used in clinical practice. Methods. This study reports the development of a Deep-Learning automatic segmentation algorithm (DLASA) to measure MD, and investigate its predictive value in a cohort of 656 diffuse large B cell lymphoma (DLBCL) patients included in the GAINED phase III prospective trial (NCT01659099). Results. After training on a series of 190 patients, the DLASA achieved a Dice coefficient of 0.97 ± 0.03. In the cohort, the median skeletal muscle index was 50.2 cm2/m2 and median muscle attenuation (MA) was 36.1 Hounsfield units (HU). No impact of sarcopenia was found on either progression free survival (PFS) or overall survival (OS). Muscular hypodensity, defined as MA below the tenth percentile according to sex, was associated with a lower OS and PFS, respectively (HR = 2.80 (95% CI 1.58–4.95), p &lt, 0.001, and HR = 2.22 (95% CI 1.43–3.45), p &lt, 0.001). Muscular hypodensity appears to be an independent risk factor for mortality in DLBCL and because of DLASA can be estimated in routine practice.
Published: 2021
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38. Clinical pharmacokinetics of methotrexate in oncology

Author: Catherine Paillard, Luc-Matthieu Fornecker, Guillaume Becker, Elise Toussaint, and Dominique Levêque
Subjects: Drug, Oncology, medicine.medical_specialty, business.industry, media_common.quotation_subject, Pharmacology, 030226 pharmacology & pharmacy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacokinetics, chemistry, 030220 oncology & carcinogenesis, Pharmacodynamics, Internal medicine, Toxicity, Antifolate, medicine, Methotrexate, Dosing, business, Pharmacogenetics, media_common, medicine.drug
Abstract: Methotrexate is an antifolate agent used in the treatment of autoimmune diseases and various types of cancers. It is a unique antiproliferative agent because it can be administered by multiple routes with a wide variation of dosing. Methotrexate pharmacokinetics have generated numerous papers focusing on descriptive data and pharmacodynamics. Methotrexate is one of the rare anticancer agents which pharmacokinetics are routinely monitoring to control excessive toxicity when administrated at high dose (>1 g/m2). The identification of transporters involved in its disposition has permitted the understanding and the prevention of most drug interactions. Pharmacogenetic factors affecting the expression of MRP2 and OATP1B1 partly explain the interindividual variability of methotrexate clearance. The remaining challenge in methotrexate pharmacokinetics is to further understand unexplained delayed renal elimination despite the implementation of preventive measures.
Published: 2017
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39. Prevalence of BTK and PLCG2 mutations in a real-life CLL cohort still on ibrutinib after 3 years: a FILO group study

Author: Vincent Levy, Marie-Sarah Dilhuydy, Gregory Lazarian, Anne Quinquenel, Rémi Letestu, Carole Fleury, Delphine Nollet, Florence Cymbalista, Luc-Matthieu Fornecker, Damien Roos-Weil, Alain Delmer, Katia Hormigos, Lise Willems, Romain Guieze, Anne-Sophie Michallet, Loic Ysebaert, Pierre Feugier, Fanny Baran-Marszak, Centre Hospitalier Universitaire de Reims (CHU Reims), Université de Reims Champagne-Ardenne (URCA), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Les Hôpitaux Universitaires de Strasbourg (HUS), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Groupe Hospitalier Universitaire Paris Seine-Saint-Denis (GHUPSSD), Adaptateurs de signalisation en hématologie (ASIH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Universités (COMUE), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Léon Bérard [Lyon], Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Faculté des Sciences Fondamentales et Biomédicales (UPD5 Sciences), Université Paris Descartes - Paris 5 (UPD5), CHADEYRON, DOMINIQUE, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Lymphocytosis, Chronic lymphocytic leukemia, Immunology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Internal medicine, medicine, Bruton's tyrosine kinase, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, medicine.disease, 3. Good health, Leukemia, chemistry, Specimen collection, 030220 oncology & carcinogenesis, Ibrutinib, Cohort, biology.protein, Sample collection, medicine.symptom, business
Abstract: Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase (BTK) and/or phospholipase Cγ2 (PLCG2) genes. Mutational information for patients still on ibrutinib is limited. We report a study aimed to provide a “snapshot” of the prevalence of mutations in a real-life CLL cohort still on ibrutinib after at least 3 years of treatment. Of 204 patients who initiated ibrutinib via an early-access program at 29 French Innovative Leukemia Organization (FILO) centers, 63 (31%) were still on ibrutinib after 3 years and 57 provided a fresh blood sample. Thirty patients had a CLL clone ≥0.5 × 109/L, enabling next-generation sequencing (NGS); BTK and PLCG2 mutations were detected in 57% and 13% of the NGS samples, respectively. After median follow-up of 8.5 months from sample collection, the presence of a BTK mutation was significantly associated with subsequent CLL progression (P = .0005 vs no BTK mutation). Our findings support that mutational analysis should be considered in patients receiving ibrutinib who have residual clonal lymphocytosis, and that clinical trials are needed to evaluate whether patients with a BTK mutation may benefit from an early switch to another treatment.
Published: 2019
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40. High‐dose therapy with autologous stem cells transplantation in Bing‐Neel syndrome: A retrospective analysis of 14 cases

Author: Luc-Matthieu Fornecker, Véronique Leblond, Laurence Simon, Olivier Tournilhac, Richard Lemal, CHU Strasbourg, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Oncology, medicine.medical_specialty, business.industry, medicine.medical_treatment, MEDLINE, Retrospective cohort study, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Hematopoietic stem cell transplantation, 3. Good health, Transplantation, 03 medical and health sciences, 0302 clinical medicine, Text mining, High dose therapy, 030220 oncology & carcinogenesis, Internal medicine, medicine, Stem cell, business, ComputingMilieux_MISCELLANEOUS, 030215 immunology, Bing–Neel syndrome
Abstract: International audience
Published: 2019
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41. Management and outcome of primary CNS lymphoma in the modern era: An LOC network study

Author: Daniel Delgadillo, Carole Soussain, Bachir Aidaoui, Eileen M Boyle, Philippe Agapé, Vincent Delwail, Agusti Alentorn, Adrien Chauchet, Olivier Casasnovas, Hassen Douzane, Franck Morschhauser, Magali Le Garff-Tavernier, Marie Blonski, Olivier Chinot, Luc Taillandier, Matthieu Peyre, Myrto Costopoulos, Chantal Campello, Fabrice Jardin, Jerome Tamburini, Aurélie Kas, Alexandra Amiel, Frédéric Charlotte, Michel Fabbro, Karima Mokhtari, Emeline Tabouret, Caroline Houillier, Valérie Touitou, Agathe Waultier, Jacques-Olivier Bay, Gandhi Damaj, Nadine Martin-Duverneuil, Lucie Oberic, Julie Abraham, Roch Houot, Hervé Ghesquières, Marie-Pierre Moles-Moreau, Remy Gressin, Corinne Haioun, Adrian Tempescul, Diane Genet, Thierry Lamy, Safia Chebrek, Philippe Colin, Anna Schmitt, Sylvain Choquet, Cécile Moluçon-Chabrot, Jean-Pierre Marolleau, Guido Ahle, Loïc Feuvret, Luc-Matthieu Fornecker, Khê Hoang-Xuan, Emmanuel Gyan, Kamel Laribi, Bertrand Mathon, Caroline Serrier, Pierre Soubeyran, Nathalie Cassoux, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de neurophysiopathologie (INP), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], 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), Institut Curie [Paris], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Adult, medicine.medical_specialty, Antimetabolites, Antineoplastic, Palliative care, Adolescent, Databases, Factual, Lymphoma, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Transplantation, Autologous, Article, Central Nervous System Neoplasms, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Antineoplastic Agents, Immunological, Internal medicine, hemic and lymphatic diseases, Outcome Assessment, Health Care, medicine, Humans, Progression-free survival, Young adult, education, Aged, Retrospective Studies, education.field_of_study, business.industry, Age Factors, Retrospective cohort study, Middle Aged, Combined Modality Therapy, Progression-Free Survival, 3. Good health, Transplantation, Clinical trial, Methotrexate, 030220 oncology & carcinogenesis, Rituximab, Neurology (clinical), France, Cranial Irradiation, business, 030217 neurology & neurosurgery, medicine.drug, Stem Cell Transplantation
Abstract: ObjectiveReal-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL.MethodsThe French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed.ResultsWe identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients 60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis.ConclusionsOur study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment.
Published: 2019
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42. Prevalence of

Author: Anne, Quinquenel, Luc-Matthieu, Fornecker, Rémi, Letestu, Loïc, Ysebaert, Carole, Fleury, Grégory, Lazarian, Marie-Sarah, Dilhuydy, Delphine, Nollet, Romain, Guieze, Pierre, Feugier, Damien, Roos-Weil, Lise, Willems, Anne-Sophie, Michallet, Alain, Delmer, Katia, Hormigos, Vincent, Levy, Florence, Cymbalista, and Fanny, Baran-Marszak
Subjects: Aged, 80 and over, Male, Phospholipase C gamma, Adenine, Middle Aged, Leukemia, Lymphocytic, Chronic, B-Cell, Pyrimidines, Piperidines, Mutation, Agammaglobulinaemia Tyrosine Kinase, Disease Progression, Humans, Pyrazoles, Female, Protein Kinase Inhibitors, Aged, Follow-Up Studies
Abstract: Mutational analyses performed following acquired ibrutinib resistance have suggested that chronic lymphocytic leukemia (CLL) progression on ibrutinib is linked to mutations in Bruton tyrosine kinase (
Published: 2019

43. PET-guided, BEACOPP

Author: René-Olivier, Casasnovas, Reda, Bouabdallah, Pauline, Brice, Julien, Lazarovici, Hervé, Ghesquieres, Aspasia, Stamatoullas, Alina, Berriolo-Riedinger, Luc-Matthieu, Fornecker, Marc, André, and Michel, Meignan
Subjects: Vincristine, Positron-Emission Tomography, Procarbazine, Humans, Cyclophosphamide, Hodgkin Disease
Published: 2019

44. Multi-omics dataset to decipher the complexity of drug resistance in diffuse large B-cell lymphoma

Author: Frédéric Bertrand, Nicodème Paul, Raoul Herbrecht, Leslie Muller, Luc-Matthieu Fornecker, Marie-Pierre Chenard, Raphael Carapito, Laurent Vallat, Sarah Cianférani, Angélique Pichot, Seiamak Bahram, Laurent Mauvieux, Christine Carapito, Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Mathématique Avancée (IRMA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)
Subjects: Adult, Male, Proteomics, 0301 basic medicine, Hexokinase 3, Adolescent, Quantitative proteomics, lcsh:Medicine, Biology, Article, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Tumor Microenvironment, medicine, [CHIM]Chemical Sciences, Humans, Metabolomics, lcsh:Science, education, Aged, Neoplasm Staging, education.field_of_study, Tumor microenvironment, Multidisciplinary, Gene Expression Profiling, lcsh:R, Computational Biology, Genomics, Middle Aged, medicine.disease, 3. Good health, Lymphoma, Gene expression profiling, Gene Ontology, Treatment Outcome, 030104 developmental biology, Drug Resistance, Neoplasm, Retreatment, Cancer cell, Cancer research, Biomarker (medicine), Female, lcsh:Q, Lymphoma, Large B-Cell, Diffuse, Diffuse large B-cell lymphoma, 030217 neurology & neurosurgery
Abstract: The prognosis of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains unsatisfactory and, despite major advances in genomic studies, the biological mechanisms underlying chemoresistance are still poorly understood. We conducted for the first time a large-scale differential multi-omics investigation on DLBCL patient’s samples in order to identify new biomarkers that could early identify patients at risk of R/R disease and to identify new targets that could determine chemorefractoriness. We compared a well-characterized cohort of R/R versus chemosensitive DLBCL patients by combining label-free quantitative proteomics and targeted RNA sequencing performed on the same tissues samples. The cross-section of both data levels allowed extracting a sub-list of 22 transcripts/proteins pairs whose expression levels significantly differed between the two groups of patients. In particular, we identified significant targets related to tumor metabolism (Hexokinase 3), microenvironment (IDO1, CXCL13), cancer cells proliferation, migration and invasion (S100 proteins) or BCR signaling pathway (CD79B). Overall, this study revealed several extremely promising biomarker candidates related to DLBCL chemorefractoriness and highlighted some new potential therapeutic drug targets. The complete datasets have been made publically available and should constitute a valuable resource for the future research.
Published: 2019
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45. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study

Author: Richard Delarue, Emmanuelle Nicolas-Virelizier, Reda Bouabdallah, Veronique Edeline, Bertrand Joly, Adrian Tempescul, Hassan Farhat, Luc-Matthieu Fornecker, Peggy Dartigues, René-Olivier Casasnovas, Laurent Martin, Franck Morschhauser, Aspasia Stamatoullas, Pauline Brice, Marc André, Alain Delmer, Michel Meignan, Nicolas Mounier, Hervé Ghesquières, Jehan Dupuis, Philippe Quittet, Krimo Bouabdallah, Julien Lazarovici, Alina Berriolo-Riedinger, Anne-Claire Gac, Alexandra Traverse-Glehen, Pierre Feugier, Thierry Lamy, Thomas Gastinne, Hervé Maisonneuve, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Université Paris-Saclay, Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Hôpital Henri Mondor, Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Sud Francilien, CHU Bordeaux [Bordeaux], Centre Léon Bérard [Lyon], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Recherche translationelle relations hôte-pathogènes, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier de Versailles André Mignot (CHV), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital René HUGUENIN (Saint-Cloud), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Reims (CHU Reims), Département de biologie et pathologie médicales [Gustave Roussy], Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Hospitalier Universitaire de Nice (CHU Nice), LYSA Imaging (Créteil) (LYSA-IM), CHU Henri Mondor, CHU Dijon, Département d'Hematologie, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CRLCC 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'Hématologie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie [Nantes], Hôpital Sud-Fancilien, CH Sud-Fancilien, Service d'hématologie, Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie Hôpital Mignot, Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CH La Roche-sur-Yon, Service d’Hématologie Clinique [CHU Pontchaillou, Rennes], Service d'hématologie et immunologie pédiatrique, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Dinant-Godinne UCL Namur, Service de cancérologie, 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 médecine nucléaire [Créteil], Université Grenoble Alpes (UGA), Département Hématologie (FNCLCC), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Groupe Régional d'Etudes sur le CANcer (GRECAN), IFR146-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse )-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Département d'Hématologie Clinique [CHU Nantes], Université Mohamed Boudiaf de M'sila, Service d’Hématologie Clinique [CHRU Nancy], Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut d'Electronique et de Télécommunications de Rennes (IETR), Université de Nantes (UN)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre hospitalier La Roche-Sur-Yon, Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'hématologie [Reims], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologie morphologique, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service de Pathologie [CHU de Dijon], Service de Médecine Interne Clermont Ferrand (MéDECINE INTERNE - CLERMONT-FERRAND), Hopital, Hôpital Archet 2 [Nice] (CHU), Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud, CH Evry-Corbeil, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, CCSD, Accord Elsevier, Service d'Hématologie Clinique (CHU de Dijon), Institut Universitaire d'Hématologie [Hôpital Saint-Louis - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d’Hématologie [Rouen], CHU Rouen, Service hématologie Créteil, CHU, Laboratoire d'Hématologie Biologique [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Service d'hématologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], 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), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Département de médecine nucléaire (Institut Curie, Saint-Cloud), Institut Curie [Paris], Hématologie clinique [CH La Roche-sur-Yon], service hématologie Strasbourg, CHU Strasbourg, Service d’Hématologie Clinique [Rennes], Service hématologie Nice, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (MGD) Service d'hématologie, CHU Henri Mondor [Créteil], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: Adult, Male, medicine.medical_specialty, Vincristine, Dacarbazine, [SDV]Life Sciences [q-bio], Salvage therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Procarbazine, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, Neoplasm Staging, business.industry, Standard treatment, medicine.disease, Hodgkin Disease, 3. Good health, Vinblastine, Drug Therapy, Computer-Assisted, [SDV] Life Sciences [q-bio], Oncology, ABVD, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Female, business, Febrile neutropenia, 030215 immunology, medicine.drug
Abstract: International audience; Background: Increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated) improves progression-free survival in patients with advanced Hodgkin lymphoma compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), but is associated with increased risks of haematological toxicity, secondary myelodysplasia or leukaemia, and infertility. We investigated whether PET monitoring during treatment could allow dose de-escalation by switching regimen (BEACOPPescalated to ABVD) in early responders without loss of disease control compared with standard treatment without PET monitoring.Methods: AHL2011 is a randomised, non-inferiority, phase 3 study done in 90 centres across Belgium and France. Eligible patients were aged 16-60 years and had newly diagnosed Hodgkin lymphoma, excluding nodular lymphocyte predominant subtype, an Eastern Cooperative Oncology Group performance status score less than 3, a life expectancy of at least 3 months, an Ann Arbor disease stage III, IV, or IIB with mediastinum-to-thorax ratio of 0·33 or greater than or extranodal localisation, and had received no previous treatment for Hodgkin lymphoma. Randomisation was unmasked and done centrally by the permuted block method. Patients were randomly assigned to standard treatment (BEACOPPescalated given every 21 days for six cycles) or PET-driven treatment. All patients received two cycles of upfront BEACOPPescalated, after which PET assessment was done (PET2). In the standard treatment group, PET2 patients completed two additional cycles of BEACOPPescalated induction therapy irrespective of PET2 findings. In the PET-driven treatment group, patients with positive PET2 scans received the further two cycles of BEACOPPescalated and those with a negative PET2 scan switched to two cycles of ABVD for the remaining induction therapy. In both treatment groups, PET at the end of induction therapy was used to decide whether to continue with consolidation therapy in those with negative scans or start salvage therapy in patients with positive scans (either two cycles of ABVD in PET2-negative patients in the PET-driven arm or two cycles of BEACOPPescalated). BEACOPPescalated consisted of bleomycin 10 mg/m2 and vincristine 1·4 mg/m2 intravenously on day 8, etoposide 200 mg/m2 intravenously on days 1-3, doxorubicin 35 mg/m2 and cyclophosphamide 1250 mg/m2 intravenously on day 1, 100 mg/m2 oral procarbazine on days 1-7, and 40 mg/m2 oral prednisone on days 1-14. ABVD was given every 28 days (doxorubicin 25 mg/m2, bleomycin 10 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2 intravenously on days 1 and 15). The primary endpoint was investigator-assessed progression-free survival. Non-inferiority analyses were done by intention to treat and per protocol. The study had a non-inferiority margin of 10%, to show non-inferiority of PET-guided treatment versus standard care with 80% power and an alpha of 2·5% (one-sided). This study is registered with ClinicalTrials.gov, number NCT01358747.Findings: From May 19, 2011, to April 29, 2014, 823 patients were enrolled-413 in the standard care group and 410 in the PET-driven group. 346 (84%) of 410 patients in the PET-driven treatment group were assigned to receive ABVD and 51 (12%) to continue receiving BEACOPPescalated after PET2. With a median follow-up of 50·4 months (IQR 42·9-59·3), 5-year progression-free survival by intention to treat was 86·2%, 95% CI 81·6-89·8 in the standard treatment group versus 85·7%, 81·4-89·1 in the PET-driven treatment group (hazard ratio [HR] 1·084, 95% CI 0·737-1·596; p=0·65) and per protocol the values were 86·7%, 95% CI 81·9-90·3 and 85·4%, 80·7-89·0, respectively (HR 1·144, 0·758-1·726; p=0·74). The most common grade 3-4 adverse events were leucopenia (381 [92%] in the standard treatment group and 387 [95%] in the PET-driven treatment group), neutropenia (359 [87%] and 366 [90%]), anaemia (286 [69%] vs 114 [28%]), thrombocytopenia (271 [66%] and 163 [40%]), febrile neutropenia (145 [35%] and 93 [23%]), infections (88 [22%] and 47 [11%]), and gastrointestinal disorders (49 [11%] and 48 [11%]). Serious adverse events related to treatment were reported in 192 (47%) patients in the standard treatment group and 114 (28%) in the PET-driven treatment group, including infections (84 [20%] of 412 vs 50 [12%] of 407) and febrile neutropenia (21 [5%] vs 23 [6%]). Six (1%) patients in the standard care group died from treatment-related causes (two from septic shock, two from pneumopathy, one from heart failure, and one from acute myeloblastic leukaemia), as did two (
Published: 2019
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46. Evaluation of the effects of chemotherapy on brain glucose metabolism in children with Hodgkin's lymphoma

Author: Izzie Jacques Namer, Luc-Matthieu Fornecker, Alban Tauty, Catherine Paillard, Vincent Noblet, and Caroline Bund
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Population, Antineoplastic Agents, Carbohydrate metabolism, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Fluorodeoxyglucose F18, Internal medicine, Positron Emission Tomography Computed Tomography, medicine, Humans, Radiology, Nuclear Medicine and imaging, education, Child, Pathological, Aged, Retrospective Studies, education.field_of_study, Chemotherapy, medicine.diagnostic_test, business.industry, Brain, Retrospective cohort study, General Medicine, Neuropsychological test, Middle Aged, medicine.disease, Hodgkin's lymphoma, Hodgkin Disease, Lymphoma, Glucose, 030220 oncology & carcinogenesis, Female, business
Abstract: Chemobrain is a recently proposed pathological entity. 18F-FDG PET/CT can show objective abnormalities to explain brain disorders caused by chemotherapy, although no study has investigated these phenomena in children to date. The main objective of the present study was to examine quantitatively the effects of chemotherapy on brain metabolism in a homogeneous population of children treated for Hodgkin's lymphoma using 18F-FDG PET/CT. In this retrospective study, we included 20 children, newly diagnosed with Hodgkin’s lymphoma, who underwent 18F-FDG PET/CT at initial staging and at least one PET/CT in follow-up. The SPM12 software provided t-maps to show the difference in metabolism between these PET/CTs. The statistical maps were analyzed with xjView software to identify the brain regions associated with the clusters detected. Altered glucose metabolism was found in the frontal, cingular, and temporoinsular regions after two cycles of chemotherapy. Results in children were compared to a group of 35 adults. For the same statistical threshold, the extent and depth of the metabolic alterations were less in the adult group than in children. 18F-FDG PET/CT is useful in providing objective data to explain brain disorders caused by chemotherapy. This could lead to better care and should be compared to neuropsychological test results.
Published: 2018

47. Tandem haematopoietic stem cell transplantation for High Risk relapsed/refractory Hodgkin Lymphoma: a LYSA study

Author: Philippe Quittet, Jerome Tamburini, Luc-Matthieu Fornecker, Pauline Brice, Isabelle Chaillol, Sandy Amorim, Marie Robin, Aurore Perrot, Olivier Tournilhac, Katell Le Du, Jean Pierre Marolleau, Bénédicte Deau, Driss Chaoui, Lucie Oberic, Jérôme Cornillon, Anne Sophie Veillard, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Immunoconjugates, Adolescent, Population, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Refractory, Recurrence, Risk Factors, Internal medicine, medicine, Refractory Hodgkin Lymphoma, Humans, Autografts, Brentuximab vedotin, education, Survival rate, ComputingMilieux_MISCELLANEOUS, Brentuximab Vedotin, education.field_of_study, business.industry, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Allografts, Hodgkin Disease, Confidence interval, 3. Good health, Survival Rate, Transplantation, surgical procedures, operative, 030220 oncology & carcinogenesis, Female, Stem cell, business, Follow-Up Studies, 030215 immunology, medicine.drug
Abstract: Tandem stem cell transplantation (SCT) is an option for high-risk relapsed/refractory Hodgkin Lymphoma (HL) patients. We evaluated the tolerance/efficacy of double autologous or autologous SCT (ASCT) followed by allogenic SCT (alloSCT) in 120 HL patients prospectively registered on a French nationwide database. Median age was 26 (14-56) years. Complete remission rate was 60%, including 33% after a single line, and another 27% after two or more salvage regimens. Partial response rate was 32%, and 8% suffered treatment failure. Overall, 115 (96%) patients underwent a first ASCT, and 73 (61%) had a tandem SCT, including alloSCT in 44 (60%) and ASCT in 29 (40%). The median follow-up was 43 months (4.8-73.7 months). The two-year progression-free survival rate for the whole population and for patients receiving tandem transplant was 56% (95% confidence interval [CI]: 46-65%) and 71% (95% CI: 49-84%), respectively. Among tandem transplants, we observed 20 deaths (17%), 10 of which were transplant-related (6 alloSCT and 4 ASCT). We suggest that tandem SCT is efficient in high-risk relapsed/refractory HL patients, although transplant-related mortality remains high. The benefit of tandem SCT should be balanced with the efficacy of Brentuximab vedotin-based post-transplant consolidative strategies in high-risk relapsed/refractory HL patients.
Published: 2018
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48. BCR-associated factors driving chronic lymphocytic leukemia cells proliferation ex vivo

Author: Cédric Schleiss, Wassila Ilias, Ouria Tahar, Yonca Güler, Laurent Miguet, Caroline Mayeur-Rousse, Laurent Mauvieux, Luc-Matthieu Fornecker, Elise Toussaint, Raoul Herbrecht, Frédéric Bertrand, Myriam Maumy-Bertrand, Thierry Martin, Sylvie Fournel, Philippe Georgel, Seiamak Bahram, Laurent Vallat, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Institut de Recherche en Mathématiques, Interactions et Applications (Labex_IRMIA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche Mathématique Avancée (IRMA), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Immunologie cellulaire et tissulaire, and Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, lcsh:Medicine, Receptors, Antigen, B-Cell, Apoptosis, Article, Cohort Studies, hemic and lymphatic diseases, Tumor Cells, Cultured, Humans, Syk Kinase, Phosphorylation, lcsh:Science, Aged, Cell Proliferation, Aged, 80 and over, B-Lymphocytes, ZAP-70 Protein-Tyrosine Kinase, lcsh:R, Middle Aged, Leukemia, Lymphocytic, Chronic, B-Cell, Case-Control Studies, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:Q, Female, STAT6 Transcription Factor, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; A chronic antigenic stimulation is believed to sustain the leukemogenic development of chronic lymphocytic leukemia (CLL) and most of lymphoproliferative malignancies developed from mature B cells. Reproducing a proliferative stimulation ex vivo is critical to decipher the mechanisms of leukemogenesis in these malignancies. However, functional studies of CLL cells remains limited since current ex vivo B cell receptor (BCR) stimulation protocols are not sufficient to induce the proliferation of these cells, pointing out the need of mandatory BCR co-factors in this process. Here, we investigated benefits of several BCR co-stimulatory molecules (IL-2, IL-4, IL-15, IL-21 and CD40 ligand) in multiple culture conditions. Our results demonstrated that BCR engagement (anti-IgM ligation) concomitant to CD40 ligand, IL-4 and IL-21 stimulation allowed CLL cells proliferation ex vivo. In addition, we established a proliferative advantage for ZAP70 positive CLL cells, associated to an increased phosphorylation of ZAP70/SYK and STAT6. Moreover, the use of a tri-dimensional matrix of methylcellulose and the addition of TLR9 agonists further increased this proliferative response. This ex vivo model of BCR stimulation with T-derived cytokines is a relevant and efficient model for functional studies of CLL as well as lymphoproliferative malignancies. Like in most mature lymphoproliferative malignancies, an antigenic stimulation is believed to drive the leukemo-genic process in chronic lymphocytic leukemia (CLL) 1-3. A restricted use of IGHV genes and the existence of ste-reotypic B cell receptor (BCR) on CLL cells 4-6 provides evidence in favor of antigenic stimulation where different microbial antigens, as well as auto-antigens, have been suspected as actors of this chronic stimulation 7. In addition , a chronic BCR self-activation has been shown in subtypes of CLL cells 8. Moreover, several signaling aberrations have been described downstream of the BCR, notably in aggressive CLL with unmutated IGHV (UM-CLL), in which the expression of ZAP70 reinforces BCR responsiveness 9-12. BCR activation, which is essential for the physiological development of lymphocytes 13 would also be indispensable for the survival and proliferation of CLL cells in vivo 2. Accordingly, withdrawal of this stimulation is believed to be responsible for the rapid spontaneous apoptosis of CLL cells ex vivo 14. The cellular consequences of this BCR activation has been extensively studied and
Published: 2018
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49. Imaging spectrum of Bing-Neel syndrome: how can a radiologist recognise this rare neurological complication of Waldenström's macroglobulinemia?

Author: Patrick Vermersch, Christine Lebrun-Frenay, Jean-Philippe Cottier, Jean-Pierre Pruvo, Laurence Simon, Aikaterini Fitsiori, C. Clerc, Damien Galanaud, Luc-Matthieu Fornecker, Jean-Louis Dietemann, F. Lafitte, Olivier Outteryck, Emmanuel Gerardin, Alexandros Karentzos, Stéphane Kremer, Jérôme De Seze, Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (BMNST), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Prevalence, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Bing–Neel syndrome, Neuroradiology, Aged, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, business.industry, Medical record, Meninges, Macroglobulinemia, Brain, Reproducibility of Results, Interventional radiology, Magnetic resonance imaging, Neurodegenerative Diseases, General Medicine, Syndrome, Middle Aged, Magnetic Resonance Imaging, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Radiological weapon, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Radiology, France, Waldenstrom Macroglobulinemia, business
Abstract: Bing–Neel syndrome (BNS) is a rare neurological complication of Waldenstrom’s macroglobulinemia. The aim of this study is to describe the spectrum of radiological manifestations of this syndrome and their prevalence in order to facilitate its early diagnosis. Twenty-four patients with BNS were diagnosed between 1994 and 2016 in eight centres in France. We retrospectively examined the medical records of these patients as well as the corresponding literature, focusing on imaging studies. Recorded data were statistically analysed and radiological findings described. The mean age of our patients was 62.4 years (35–80 years). The vast majority of patients were men, with a male to female ratio of 9:1. Findings included parenchymal or meningeal involvement or both. The most common finding was leptomeningeal infiltration, either intracranial or spinal, with a prevalence reaching 70.8%. Dural involvement was present in 37.5% of patients. In 41.7% (10/24) of patients, there was parenchymal involvement with a higher prevalence of brain comparing to medullar involvement (33.3% and 23.1% respectively). High T2 signal of the parenchyma was identified in 41.7% of patients and high signal in diffusion was evident in 25% of them. Intraorbital or periorbital involvement was also detected in four cases. A proposition regarding the appropriate imaging protocol completed our study. BNS’s diagnosis remains challenging. Central nervous system MRI findings in the setting of known or suspected Waldenstrom’s macroglobulinemia appear to be highly suggestive of BNS and appropriate imaging protocols should be implemented for their depiction. • Diagnosis of Bing–Neel syndrome (BNS) remains challenging and recent expert recommendations include MRI in the diagnostic criteria for the syndrome. • The most common radiological manifestations of BNS are leptomeningeal/dural infiltration or parenchymal involvement of brain or spinal cord, but many atypical forms may exist with various presentations. • Appropriate imaging protocol for BNS should include enhanced MRI studies of both brain and spine.
Published: 2018
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50. Should Adolescents with Hodgkin Lymphoma Be Treated as Old Children or Young Adults?

Author: Judith Landman-Parker, Odile Oberlin, Patrice Carde, Christophe Fermé, Berthe M. P. Aleman, Thierry Leblanc, John M. M. Raemaekers, Catherine Sebban, Evert M. Noordijk, Luc-Matthieu Fornecker, Houchingue Eghbali, Josette Brière, and Michel Henry-Amar
Published: 2018
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