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1. Preclinical in vivo assessment of the activity of AZD7442 anti-SARS-CoV-2 monoclonal antibodies against Omicron sublineages

Author

Jean-Sélim Driouich, Maxime Cochin, Guillaume Lingas, Léa Luciani, Cécile Baronti, Ornéllie Bernadin, Magali Gilles, Paola Mariela Saba Villarroel, Grégory Moureau, Paul-Rémi Petit, Axelle Dupont, Jacques Izopet, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Amandine le Bourgeois, Christophe Richez, Lionel Couzi, Aliénor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Dany Anglicheau, Morgane Cheminant, Stéphanie Nguyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Josephine Tine, Joe Miantezila Basilua, Denis Angoulvant, Coralie Tardivon, Gilles Blancho, Guillaume Martin-Blondel, Yazdan Yazdanpanah, France Mentré, Vincent Lévy, Franck Touret, Jérémie Guedj, Xavier de Lamballerie, and Antoine Nougairède

Subjects
Preclinical animal model, Monoclonal antibody, SARS-CoV-2, Omicron sublineages, AZD7442, Clinical therapeutics, Therapeutics. Pharmacology, RM1-950
Abstract

Therapeutic monoclonal antibodies have been successful in protecting vulnerable populations against SARS-CoV-2. However, their effectiveness has been hampered by the emergence of new variants. To adapt the therapeutic landscape, health authorities have based their recommendations mostly on in vitro neutralization tests. However, these do not provide a reliable understanding of the changes in the dose-effect relationship and how they may translate into clinical efficacy. Taking the example of EvusheldTM (AZD7442), we aimed to investigate how in vivo data can provide critical quantitative results and project clinical effectiveness. We used the Golden Syrian hamster model to estimate 90 % effective concentrations (EC90) of AZD7442 in vivo against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5 variants. While our in vivo results confirmed the partial loss of AZD7442 activity for BA.1 and BA.2, they showed a much greater loss of efficacy against BA.5 than that obtained in vitro. We analyzed in vivo EC90s in perspective with antibody levels measured in a cohort of immunocompromised patients who received 300 mg of AZD7442. We found that a substantial proportion of patients had serum levels of anti-SARS-CoV-2 spike protein IgG above the estimated in vivo EC90 for BA.1 and BA.2 (21 % and 92 % after 1 month, respectively), but not for BA.5. These findings suggest that AZD7442 is likely to retain clinical efficacy against BA.2 and BA.1, but not against BA.5. Overall, the present study illustrates the importance of complementing in vitro investigations by preclinical studies in animal models to help predict the efficacy of monoclonal antibodies in humans.

Published
2024
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2. Bone marrow graft versus peripheral blood graft in haploidentical hematopoietic stem cells transplantation: a retrospective analysis in1344 patients of SFGM-TC registry

Author

Claire Lacan, Jérôme Lambert, Edouard Forcade, Marie Robin, Patrice Chevallier, Sandrine Loron, Claude-Éric Bulabois, Corentin Orvain, Patrice Ceballos, Etienne Daguindau, Amandine Charbonnier, Yves Chalandon, Marc Bernard, Célestine Simand, Marie-Thérèse Rubio, Pascal Turlure, Johan Maertens, Anne Huynh, Michael Loschi, Jacques-Olivier Bay, Gaëlle Guillerm, Mustafa Alani, Cristina Castilla-Llorente, Xavier Poiré, Sylvain Chantepie, Natacha Maillard, Yves Beguin, Ambroise Marçais, Jérôme Cornillon, Jean-Valère Malfuson, Sébastien Maury, Nathalie Meuleman, Alban Villate, Mohammed-Amine Bekadja, Anouk Walter-Petrich, Nathalie Jacque, Micha Srour, Raynier Devillier, and Stéphanie Nguyen

Subjects
Haploidentical hematopoietic stem cell transplantation, Graft source, Bone marrow, Peripheral stem cell, Anti-thymoglobulin, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract The use of peripheral blood (PB) or bone marrow (BM) stem cells graft in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remains controversial. Moreover, the value of adding anti-thymoglobulin (ATG) to PTCy is unknown. A total of 1344 adult patients received an unmanipulated haploidentical transplant at 37 centers from 2012 to 2019 for hematologic malignancy. We compared the outcomes of patients according to the type of graft, using a propensity score analysis. In total population, grade II–IV and III–IV acute GVHD (aGVHD) were lower with BM than with PB. Grade III–IV aGVHD was lower with BM than with PB + ATG. All outcomes were similar in PB and PB + ATG groups. Then, in total population, adding ATG does not benefit the procedure. In acute leukemia, myelodysplastic syndrome and myeloproliferative syndrome (AL-MDS-MPS) subgroup receiving non-myeloablative conditioning, risk of relapse was twice greater with BM than with PB (51 vs. 22%, respectively). Conversely, risk of aGVHD was greater with PB (38% for aGVHD II–IV; 16% for aGVHD III–IV) than with BM (28% for aGVHD II–IV; 8% for aGVHD III–IV). In this subgroup with intensified conditioning regimen, risk of relapse became similar with PB and BM but risk of aGVHD III–IV remained higher with PB than with BM graft (HR = 2.0; range [1.17–3.43], p = 0.012).

Published
2024
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3. On behalf of the SFGM‐TC: Real‐life use of third‐party virus‐specific T‐cell transfer in immunocompromised transplanted patients

Author

Esther Hazane Leroyer, Nadine Petitpain, Stéphane Morisset, Bénédicte Neven, Martin Castelle, Sarah Winter, Laetitia Souchet, Véronique Morel, Marie Le Cann, Mony Fahd, Karima Yacouben, Françoise Mechinaud, Marie Ouachée‐Chardin, Cécile Renard, Hélène Labussière Wallet, Marie Angoso, Charlotte Jubert, Patrice Chevallier, Alexandra Léger, Fanny Rialland, Nathalie Dhedin, Christine Robin, Sébastien Maury, Florence Beckerich, David Beauvais, Thomas Cluzeau, Michaël Loschi, Alina Fernster, Marcelo De Carvalho Bittencourt, Maxime Cravat, Karin Bilger, Laurence Clément, Véronique Decot, Mélanie Gauthier, Anne Legendre, Jérôme Larghero, Amani Ouedrani, Guillaume Martin‐Blondel, Cécile Pochon, Loïc Reppel, Hélène Rouard, Stéphanie Nguyen‐Quoc, Jean‐Hugues Dalle, Maud D'Aveni, and Danièle Bensoussan

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2024
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4. S232: EFFICACY AND TOXICITY OF CAR-T CELLS IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMAS, A NEW REFERENCE: THE FRENCH EXPERIENCE OF THE NATIONAL LOC NETWORK

Author

Sylvain Choquet, Carole Soussain, Magali Legarff-Tavernier, Roberta DI Blasi, Laetitia Souchet, Damien Roos-Weil, Veronique Morel Malek, Madalina Uzunov, Carole Metz, Stéphanie Nguyen-Quoc, Nicolas Gauthier, Lise Willems, Agathe Waultier Rascalou, Celia Salanoubat, Roch Houot, Renata Ursu, Lionel Galicier, Maryline Barrie, Guido Ahle, Blandine Guffroy, Marion Alcantara, Khe Hoang-Xuan, and Caroline Houillier

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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5. Pre-exposure prophylaxis with tixagevimab/cilgavimab (AZD7442) prevents severe SARS-CoV-2 infection in recipients of allogeneic hematopoietic stem cell transplantation during the Omicron wave: a multicentric retrospective study of SFGM-TC

Author

Ludovic Jondreville, Maud D’Aveni, Hélène Labussière-Wallet, Amandine Le Bourgeois, Alban Villate, Ana Berceanu, Silvia-Maria Bezsera, Anne Thiebaut, Marion Boissard-Simonet, Marlène Legrand, Jérôme Cornillon, Marie-Thérèse Rubio, Patrice Chevallier, and Stéphanie Nguyen

Subjects
SARS-CoV-2, Allogeneic stem cell transplantation, Pre-exposure prophylaxis, AZD7442, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Since the emergence of the Omicron variant of SARS-CoV-2, though considered less virulent, hospitalization and death rates among immunocompromised patients remain high, especially for poor responders to vaccination. We conducted a retrospective multicentric study to evaluate pre-exposure prophylaxis with AZD7442 (tixagevimab/cilgavimab) for preventing COVID-19 in adult allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Among the 161 patients of our cohort, 22 (14%) contracted COVID-19 after a median follow-up of 105 days, but no severe form was observed. Only one major adverse event was reported: an acute coronary syndrome, resolved without sequelae. Pending randomized controlled trial results, our data support the use of AZD7442 as pre-exposure prophylaxis for COVID-19 during Omicron wave in allo-HSCT patients who failed to develop humoral immunity to vaccination, to prevent severe and potentially lethal forms of SARS-CoV-2 infection.

Published
2022
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6. CAR T-cell therapy for central nervous system lymphomas: blood and cerebrospinal fluid biology, and outcomes

Author

Claire Lacan, Jonathan Caron, Nadine Tarantino, Baptiste Fouquet, Mustapha Cherai, Christophe Parizot, Véronique Morel, Laetitia Souchet, Madalina Uzunov, Guy Gorochov, Stéphanie Nguyen-Quoc, Elise Sourdeau, Vincent Vieillard, Makoto Miyara, Angélique Vinit, Silvia Solorzano, Carole Soussain, Caroline Houillier, Carole Metz, Brigitte Autran, Elena Litvinova, Magali Le Garff-Tavernier, Françoise Norol, Damien Roos-Weil, Sylvan Choquet, Amélie Guihot, and Marine Baron

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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7. Primary Cancer Matters in Therapy-related Myeloid Neoplasm Patients Receiving Allogeneic Hematopoietic Cell Transplantation: A Study From the Chronic Malignancies Working Party of the EBMT

Author

Marie Robin, Liesbeth C. de Wreede, Thomas Schroeder, Friedrich Stölzel, Nicolaus Kröger, Linda Koster, Uwe Platzbecker, Jürgen Finke, Arnold Ganser, Didier Blaise, Fabio Ciceri, Johan Maertens, Hélène Labussière Wallet, Junfeng Wang, Patrice Chevallier, Jakob Passweg, Jan J Cornelissen, Stéphanie Nguyen, Edouard Forcade, Amandine Charbonnier, Francesca Bonifazi, Patrick Hayden, Donal P. McLornan, and Ibrahim Yakoub-Agha

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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8. Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients

Author

Florent Malard, Anne Vekhoff, Simona Lapusan, Francoise Isnard, Evelyne D’incan-Corda, Jérôme Rey, Colombe Saillard, Xavier Thomas, Sophie Ducastelle-Lepretre, Etienne Paubelle, Marie-Virginie Larcher, Clément Rocher, Christian Recher, Suzanne Tavitian, Sarah Bertoli, Anne-Sophie Michallet, Lila Gilis, Pierre Peterlin, Patrice Chevallier, Stéphanie Nguyen, Emilie Plantamura, Lilia Boucinha, Cyrielle Gasc, Mauricette Michallet, Joel Dore, Ollivier Legrand, and Mohamad Mohty

Subjects
Science
Abstract

The combination of chemotherapy and broad-spectrum antibiotics induces gut microbiota (GM) dysbiosis in acute myeloid leukaemia (AML) leading to additional complications. Here, the authors report the efficacy in GM restoration and safety of autologous faecal microbiota transfer in treated AML patients in a phase II clinical trial.

Published
2021
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9. Role and Modulation of NK Cells in Multiple Myeloma

Author

Marie Thérèse Rubio, Adèle Dhuyser, and Stéphanie Nguyen

Subjects
myeloma, NK cells, immunomodulation, cell therapy, immunotherapy, Medicine
Abstract

Myeloma tumor cells are particularly dependent on their microenvironment and sensitive to cellular antitumor immune response, including natural killer (NK) cells. These later are essential innate lymphocytes implicated in the control of viral infections and cancers. Their cytotoxic activity is regulated by a balance between activating and inhibitory signals resulting from the complex interaction of surface receptors and their respective ligands. Myeloma disease evolution is associated with a progressive alteration of NK cell number, phenotype and cytotoxic functions. We review here the different therapeutic approaches that could restore or enhance NK cell functions in multiple myeloma. First, conventional treatments (immunomodulatory drugs-IMids and proteasome inhibitors) can enhance NK killing of tumor cells by modulating the expression of NK receptors and their corresponding ligands on NK and myeloma cells, respectively. Because of their ability to kill by antibody-dependent cell cytotoxicity, NK cells are important effectors involved in the efficacy of anti-myeloma monoclonal antibodies targeting the tumor antigens CD38, CS1 or BCMA. These complementary mechanisms support the more recent therapeutic combination of IMids or proteasome inhibitors to monoclonal antibodies. We finally discuss the ongoing development of new NK cell-based immunotherapies, such as ex vivo expanded killer cell immunoglobulin-like receptors (KIR)-mismatched NK cells, chimeric antigen receptors (CAR)-NK cells, check point and KIR inhibitors.

Published
2021
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10. Allogeneic stem cell transplantation for peripheral T cell lymphomas: a retrospective study in 285 patients from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Author

Anne-Claire Mamez, Axelle Dupont, Didier Blaise, Patrice Chevallier, Edouard Forcade, Patrice Ceballos, Mohamad Mohty, Felipe Suarez, Yves Beguin, Regis Peffault De Latour, Marie-Thérèse Rubio, Olivier Tournilhac, and Stéphanie Nguyen

Subjects
Allogeneic stem cell transplantation, Peripheral T cell lymphoma, Retrospective analysis, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Peripheral T cell lymphomas form a heterogeneous group with a usually dismal prognostic. The place of allogeneic stem cell transplantation to treat PTCL is debated. Methods We retrospectively analyzed the overall survival (OS), event-free survival (EFS), relapse, and transplant-related mortality (TRM) and associated variables in 285 adults with non-primary cutaneous PTCL (PCTL-NOS (39%), angioimmunoblastic T cell lymphomas (29%), anaplastic T cell lymphomas (15%), and other subtypes (17%)), who received alloSCT in 34 centers between 2006 and 2014. Results AlloSCT was given as part of front-line therapy (n = 138) to 93 patients in first complete response (CR) and 45 in first partial response (PR), and of salvage therapy (n = 147) to 116 patients for second or more CR/PR and 31 for progressive disease. Reduced-intensity conditioning (RIC) was given to 172 patients (62%), while 107 (38%) received myeloablative conditioning (MAC). The median follow-up was 72.4 months. The 2- and 4-year OS were 65% and 59%, respectively, and the cumulative incidence of relapse was 18% after 1 year and 19% after 2 years. TRM was 21% at 1 year, 24% after 2 years, and 28% after 4 years. In multivariate analysis, grade III–IV acute GvHD (HR = 2.57, 95% CI 1.53–4.31; p = 0.00036), low Karnofsky score < 80% (HR = 5.14, 95% CI 2.02–13.06; p = 0.00058), and progressive disease status before transplant (HR = 2.21, 95% CI 1.25–3.89; p = 0.0062) were significantly associated with a reduced OS. Conclusions The data demonstrate in the largest retrospective cohort of non-cutaneous PTCL so far reported that alloSCT after RIC or MAC is an effective strategy, even in chemoresistant patients.

Published
2020
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11. CAR-NK Cells: A Chimeric Hope or a Promising Therapy?

Author

Mohamad Sabbah, Ludovic Jondreville, Claire Lacan, Francoise Norol, Vincent Vieillard, Damien Roos-Weil, and Stéphanie Nguyen

Subjects
natural killer cells, CAR-NK, immunotherapy, leukemia, lymphoma, allogenic CAR, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Immunotherapy with chimeric antigen receptor-engineered T cells (CAR-T) has revolutionized the treatment landscape of relapsed/refractory B-cell malignancies. Nonetheless, the use of autologous T cells has certain limitations, including the variable quality and quantity of collected effector T cells, extended time of cell processing, limited number of available CAR cells, toxicities, and a high cost. Thanks to their powerful cytotoxic capabilities, with proven antitumor effects in both haploidentical hematopoietic stem cell transplantation and adoptive cell therapy against solid tumors and hematological malignancies, Natural Killer cells could be a promising alternative. Different sources of NK cells can be used, including cellular lines, cord blood, peripheral blood, and induced pluripotent stem cells. Their biggest advantage is the possibility of using them in an allogeneic context without major toxic side effects. However, the majority of the reports on CAR-NK cells concern preclinical or early clinical trials. Indeed, NK cells might be more difficult to engineer, and the optimization and standardization of expansion and transfection protocols need to be defined. Furthermore, their short persistence after infusion is also a major setback. However, with recent advances in manufacturing engineered CAR-NK cells exploiting their cytolytic capacities, antibody-dependent cellular cytotoxicity (ADCC), and cytokine production, “off-the-shelf” allogeneic CAR-NK cells can provide a great potential in cancer treatments.

Published
2022
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12. Sexual and Emotional Health after Allogeneic Hematopoietic Cell Transplantation: A Comprehensive Review and Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

Author

Tamim Alsuliman, Ludovic Jondreville, Caroline Baylet, Marie-Pierre Dann, Natacha De Bentzmann, Marie-Laure Fontoura, Carole Genty, Anne Huynh, Diane Ibled, Ibrahim Yakoub-Agha, Lara Mercier, Catherine Poirot, Sophie Porcheron, Catherine Tourette-Turgis, Jean-Paul Vernant, Dominique Vexiau-Robert, and Stéphanie Nguyen

Subjects
sexual life, allogeneic hematopoietic cell transplantation, genital chronic GVHD, SFGM-TC, guidelines, Medicine
Abstract

A person’s sexual and emotional life is greatly impacted after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This topic is not addressed very much by patients and caregivers. Physical, endocrine and genital chronic graft versus host disease (cGVHD)-related disorders are multiple and intertwined with psychological disorders. The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) has issued recommendations for a better gynecological monitoring of female recipients after allo-HCT. A patient booklet was also offered to patients in the form of questions and answers to facilitate discussions between patients and caregivers and to improve the management of sexual and emotional life after transplant.

Published
2022
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13. Spike Gene Evolution and Immune Escape Mutations in Patients with Mild or Moderate Forms of COVID-19 and Treated with Monoclonal Antibodies Therapies

Author

Aude Jary, Stéphane Marot, Antoine Faycal, Sacha Leon, Sophie Sayon, Karen Zafilaza, Emna Ghidaoui, Stéphanie Nguyen Quoc, Safaa Nemlaghi, Sylvain Choquet, Martin Dres, Valérie Pourcher, Vincent Calvez, Helga Junot, Anne-Geneviève Marcelin, and Cathia Soulié

Subjects
COVID-19, SARS-CoV-2, monoclonal antibodies therapy, spike gene, immune escape mutation, Q493R, Microbiology, QR1-502
Abstract

We explored the molecular evolution of the spike gene after the administration of anti-spike monoclonal antibodies in patients with mild or moderate forms of COVID-19. Four out of the 13 patients acquired a mutation during follow-up; two mutations (G1204E and E406G) appeared as a mixture without clinical impact, while the Q493R mutation emerged in two patients (one receiving bamlanivimab and one receiving bamlanivimab/etesevimab) with fatal outcomes. Careful virological monitoring of patients treated with mAbs should be performed, especially in immunosuppressed patients.

Published
2022
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14. Efficacy of minimal residual disease driven immune-intervention after allogeneic hematopoietic stem cell transplantation for high-risk chronic lymphocytic leukemia: results of a prospective multicenter trial

Author

Olivier Tournilhac, Magali Le Garff-Tavernier, Stéphanie Nguyen Quoc, Edouard Forcade, Patrice Chevallier, Faezeh Legrand-Izadifar, Gandhi Laurent Damaj, David Michonneau, Cécile Tomowiak, Cécile Borel, Corentin Orvain, Pascal Turlure, Rabah Redjou, Gaëlle Guillerm, Laure Vincent, Celestine Simand, Richard Lemal, Claire Quiney, Patricia Combes, Bruno Pereira, Laure Calvet, Aurélie Cabrespine, Jacques-Olivier Bay, Véronique Leblond, Nathalie Dhédin, French Innovative Leukemia Organization (FILO), and Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

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

Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative and useful strategy in high-risk relapsing CLL. Minimal Residual Disease (MRD) assessment at 12 months post-HSCT is predictive of relapse. This phase 2 study aimed to achieve M12 MRD negativity (MRDneg) using MRD-driven immune-intervention (Md-PII) algorithm based on serial flow-cytometry blood MRD, involving cyclosporine tapering followed if failure by donor lymphocytes infusions. Patients had high-risk CLL according to 2006 EBMT consensus, in complete or partial response with lymphadenopathy < 5 cm and comorbidity score ≤ 2. Donors were HLA-matched sibling or matched unrelated (10/10). Forty-two enrolled patients with either 17p deletion (front-line, n=11; relapse n=16) or other high-risk relapse (n=15) received reduced intensity-conditioning regimen before HSCT and were submitted to Md-PII. M12-MRDneg status was achieved in 64% versus 14.2% before HSCT. With a median follow-up of 36 months (range, 19-53), 3-year overall survival, non-relapse mortality and cumulative incidence of relapse are 86.9% (95%CI, 70.8-94.4), 9.5% (95%CI, 3.7-23.4) and 29.6% (95%CI, 17.3-47.7). Incidence of 2-year limited and extensive chronic graft versus host disease (cGVHD) is 38% (95%CI, 23-53) and 23% (95%CI, 10-36) including 2 cases post Md-PII. Fifteen patients converted to MRDneg either after CsA withdrawal (n=12) or after cGVHD (n=3). As a time-dependent variable, MRDneg achievement at any time-point correlates with reduced relapse (HR=0.14 [0.04-0.53], p=0.004) and improvement of both progression free (HR=0.18 [0.06-0.6], p

Published
2020
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15. Hematopoietic stem cell transplantation for patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab: a retrospective study of 21 patients from SFGM-TC centers

Author

Nicolas Vallet, Flore Sicre de Fontbrune, Michaël Loschi, Deborah Desmier, Alban Villate, Fiorenza Barraco, Patrice Chevallier, Louis Terriou, Ibrahim Yakoub-Agha, Annalisa Ruggeri, Mohamad Mohty, Natacha Maillard, Pierre-Simon Rohrlich, Patrice Ceballos, Stéphanie Nguyen, Xavier Poiré, Gaëlle Guillerm, Reza Tabrizi, Jonathan Farhi, Raynier Devillier, Marie-Thérèse Rubio, Gérard Socié, and Régis Peffault de Latour

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2018
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16. Hepatitis E and Allogeneic Hematopoietic Stem Cell Transplantation: A French Nationwide SFGM-TC Retrospective Study

Author

Aliénor Xhaard, Anne-Marie Roque-Afonso, Vincent Mallet, Patricia Ribaud, Stéphanie Nguyen-Quoc, Pierre-Simon Rohrlich, Reza Tabrizi, Johanna Konopacki, Séverine Lissandre, Florence Abravanel, Régis Peffault de Latour, and Anne Huynh

Subjects
allogeneic hematopoietic stem transplantation, hepatitis E, Microbiology, QR1-502
Abstract

Usually self-limited, hepatitis E virus (HEV) infection may evolve to chronicity and cirrhosis in immunosuppressed patients. HEV infection has been described in solid-organ transplantation and hematology patients, but for allogeneic hematopoietic stem cell transplant (alloHSCT) recipients, only small cohorts are available. This retrospective nationwide multi-center series aimed to describe HEV diagnostic practices in alloHSCT French centers, and the course of infection in the context of alloHSCT. Twenty-nine out of 37 centers participated. HEV search in case of liver function tests (LFT) abnormalities was never performed in 24% of centers, occasionally in 55%, and systematically in 21%. Twenty-five cases of active HEV infection were diagnosed in seven centers, all because of LFT abnormalities, by blood nucleic acid testing. HEV infection was diagnosed in three patients before alloHSCT; HEV infection did not influence transplantation planning, and resolved spontaneously before or after alloHSCT. Twenty-two patients were diagnosed a median of 283 days after alloHSCT. Nine patients (41%) had spontaneous viral clearance, mostly after immunosuppressive treatment decrease. Thirteen patients (59%) received ribavirin, with sustained viral clearance in 11/12 evaluable patients. We observed three HEV recurrences but no HEV-related death or liver failure, nor evolution to cirrhosis.

Published
2019
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17. CAR T‐cell therapy induces a high rate of prolonged remission in relapsed primary CNS lymphoma: Real‐life results of the LOC network.

Author

Choquet, Sylvain, Soussain, Carole, Azar, Nabih, Morel, Véronique, Metz, Carole, Ursu, Renata, Waultier‐Rascalou, Agathe, di Blasi, Roberta, Houot, Roch, Souchet, Laetitia, Roos‐Weil, Damien, Uzunov, Madalina, Quoc, Stéphanie Nguyen, Jacque, Nathalie, Boussen, Inès, Gauthier, Nicolas, Ouzegdouh, Maya, Blonski, Marie, Campidelli, Arnaud, and Ahle, Guido

Published
2024
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18. Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party

Author

Schetelig, Johannes, Chevallier, Patrice, van Gelder, Michel, Hoek, Jennifer, Hermine, Olivier, Chakraverty, Ronjon, Browne, Paul, Milpied, Noel, Malagola, Michele, Socié, Gerard, Delgado, Julio, Deconinck, Eric, Damaj, Ghandi, Maury, Sebastian, Beelen, Dietrich, Quoc, Stéphanie Nguyen, Shankara, Paneesha, Brecht, Arne, Mayer, Jiri, Hunault-Berger, Mathilde, Bittenbring, Jörg, Thieblemont, Catherine, Lepretre, Stéphane, Baldauf, Henning, de Wreede, Liesbeth C., Tournilhac, Olivier, Yakoub-Agha, Ibrahim, Kröger, Nicolaus, and Dreger, Peter

Published
2021
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19. 2367. Six-month Humoral Response Following Two Or Three Doses Of Covid-19 Vaccines As Primary Vaccination Followed Or Not By a Booster Dose In Specific Populations – ANRS0001S COV-POPART Cohort Study

Author

LOUBET, Paul, primary, Gilbert, Camille, additional, Laplaud, David, additional, Laville, Martine, additional, Laviolle, Bruno, additional, Lelièvre, Jean-Daniel, additional, Blay, Jean-Yves, additional, Barrou, Benoit, additional, Terrier, Benjamin, additional, Quoc, Stéphanie Nguyen, additional, Barquin, Aude, additional, Moins, Cécile, additional, Tartour, Eric, additional, de Lamballerie, Xavier, additional, Launay, Odile, additional, and Wittkop, L I nda, additional

Published
2023
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20. One-month humoral response following two or three doses of messenger RNA coronavirus disease 2019 vaccines as primary vaccination in specific populations in France: first results from the Agence Nationale Recherche contre le Sida (ANRS)0001S COV-POPART cohort

Author

Loubet, Paul, Wittkop, Linda, Ninove, Laetitia, Chalouni, Mathieu, Barrou, Benoit, Blay, Jean-Yves, Hourmant, Maryvonne, Thouvenot, Eric, Laville, Martine, Laviolle, Bruno, Lelievre, Jean-Daniel, Morel, Jacques, Quoc, Stéphanie Nguyen, Spano, Jean-Philippe, Terrier, Benjamin, Thiebaut, Anne, Viallard, Jean-Francois, Vrtovsnik, François, Circosta, Sophie, Esterle, Laure, Levier, Axel, Vanhems, Philippe, Tartour, Eric, Parfait, Beatrice, de Lamballerie, Xavier, and Launay, Odile

Published
2023
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22. 1087: TBI-based conditioning regimen vs chemotherapy prior to transplant in ALL. A study from the SFGM-TC.

Author

Belkacemi, Yazid, Debbi, Kamel, To, Nhu Hanh, Coraggio, Gabriele, Cherif, Mohamed Aziz, Tour, Regis Peffault de La, Quero, Laurent, Labussiere-Wallet, Helene, Martel-Lafay, Isabelle, Beauvais, David, Mirabel, Xavier, Fourcade, Edouard, Batard, Stephanie, Devillier, Raynier, Gonzague-Casabianca, Laurence, Chevallier, Patrice, Guimas, Valentine, Mohty, Mohamad, Maertens, Johan, Poire, Xavier, Ceballos, Patrice, Castilla-Llorente, Cristina, Quoc, Stephanie Nguyen, Robin, Marie, and Loganadane, Gokoulakrichenane

Published
2024
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23. Correction to: Idelalisib treatment prior to allogeneic stem cell transplantation for patients with chronic lymphocytic leukemia: a report from the EBMT chronic malignancies working party

Author

Schetelig, Johannes, Chevallier, Patrice, van Gelder, Michel, Hoek, Jennifer, Hermine, Olivier, Chakraverty, Ronjon, Browne, Paul, Milpied, Noel, Malagola, Michele, Socié, Gerard, Delgado, Julio, Deconinck, Eric, Damaj, Ghandi, Maury, Sebastian, Beelen, Dietrich, Quoc, Stéphanie Nguyen, Shankara, Paneesha, Brecht, Arne, Mayer, Jiri, Hunault-Berger, Mathilde, Bittenbring, Jörg, Thieblemont, Catherine, Lepretre, Stéphane, Baldauf, Henning, de Wreede, Liesbeth C., Tournilhac, Olivier, Yakoub-Agha, Ibrahim, Kröger, Nicolaus, and Dreger, Peter

Published
2022
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24. Salvage haploidentical or cord‐blood allogeneic stem cell transplantation after a prior alternative allograft in hematologic malignancies: A retrospective study from the SFGM‐TC

Author

Doriane Cavalieri, Marie‐Thérèse Rubio, Alexandrine Corriger, Bruno Pereira, Aurélie Cabrespine, Marie Robin, Hélène Labussière‐Wallet, Anne Calleja, Edouard Forcade, Patrice Chevallier, Gaelle Guillerm, Ana Berceanu, Claude‐Eric Bulabois, Natacha Maillard, Stéphanie Nguyen, Nicole Raus, Hélène Schoemans, Jacques‐Olivier Bay, and Aurélie Ravinet

Subjects
Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Graft vs Host Disease, Hematology, General Medicine, Neoplasm Recurrence, Local, Allografts, Retrospective Studies
Abstract

Haploidentical (haplo-) donors and cord-blood (CB) stem cells provide alternative transplant options in patients lacking an HLA-matched donor. In case of relapse or graft failure after a first alternative allogeneic hematopoietic stem cell transplant (HSCT), a second alternative HSCT (HSCT2) is rarely considered due to a high risk of toxicity.A retrospective French multicentre study was performed, including patients with hematologic malignancies who underwent two consecutive HSCT from alternative donors. All data were exported from the national ProMISE database between 2000 and 2016.Forty-three patients (61.4%) received a CB-HSCT2 and 27 (38.6%) a haplo-HSCT2. Indications for HSCT were graft failure (51.4%) or disease progression (48.6%). Two-years probabilities of overall survival, progression-free survival and toxicity-related mortality were 18.5%, 17.8% and 55.8%, respectively. In multivariate analysis, complete remission status at HSCT2 and year of HSCT2 ≥ 2012 were significantly associated with a better outcome (with respectively hazard ratio [HR] = 0.42, p = .002 and HR = 0.5, p = .051).Neither the indication of HSCT2 nor the source of stem cell was more advantageous towards overall patient survival. A salvage haploidentical or cord-blood stem cell transplantation is a high-risk procedure, that may be considered for patients achieving a complete remission before receiving the second HSCT.

Published
2022

25. Immune stimulation during chemotherapy increases incidence of acute graft versus host disease in acute myeloid leukemia: A study on behalf of SFGM-TC and ALFA

Author

Wang, Lining, Raffoux, Emmanuel, Thomas, Xavier, Yakoub-Agha, Ibrahim, Bouhris, Jean-Henri, de Botton, Stéphane, Michallet, Mauricette, Quoc, Stéphanie Nguyen, Chantepie, Sylvain, Deconinck, Eric, Caillot, Denis, Turlure, Pascal, Vigouroux, Stéphane, Pigneux, Arnaud, Huynh, Anne, Malfuson, Jean-Valère, Loschi, Michael, Socie, Gerard, Dombret, Hervé, de la Tour, Régis Peffault, and Cluzeau, Thomas

Published
2017
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27. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study

Author

Adèle de Masson, Marie Beylot-Barry, Caroline Ram-Wolff, Jean-Baptiste Mear, Stéphane Dalle, Michel d'Incan, Saskia Ingen-Housz-Oro, Corentin Orvain, Julie Abraham, Olivier Dereure, Amandine Charbonnier, Jérôme Cornillon, Christine Longvert, Stéphane Barete, Serge Boulinguez, Ewa Wierzbicka-Hainaut, François Aubin, Marie-Thérèse Rubio, Marc Bernard, Aline Schmidt-Tanguy, Roch Houot, Anne Pham-Ledard, David Michonneau, Pauline Brice, Hélène Labussière-Wallet, Jean-David Bouaziz, Florent Grange, Hélène Moins-Teisserenc, Katayoun Jondeau, Laurence Michel, Samia Mourah, Maxime Battistella, Etienne Daguindau, Michael Loschi, Alexandra Picard, Nathalie Franck, Natacha Maillard, Anne Huynh, Stéphanie Nguyen, Ambroise Marçais, Guillaume Chaby, Patrice Ceballos, Yannick Le Corre, Sébastien Maury, Jacques-Olivier Bay, Henri Adamski, Emmanuel Bachy, Edouard Forcade, Gérard Socié, Martine Bagot, Sylvie Chevret, and Régis Peffault de Latour

Subjects
General Medicine
Published
2023

28. Allogeneic Hematopoietic Stem Cell Transplantation for Adults with Therapy-Related Acute Myeloid Leukemia: a Retrospective Multicentre Study on behalf of the SFGM-TC

Author

Emmanuelle Tavernier, Gaëlle Rey, Elisabeth Daguenet, Paul Bonjean, Raynier Devillier, Nathalie Fegueux, Edouard Forcade, micha sr, patrice chevalier, marie robin, Felipe Suarez, Jean-Baptiste Micol, helene labussiere, Karin Bilger, Etienne Daguindau, Jacques Olivier Bay, Amandine Fayard, Claude-Eric BULABOIS, Stéphanie Nguyen-Quoc, Alexis Genthon, Corentin Orvain, Pascal TURLURE, Michael Loschi, Xavier Poire, Gaella Guillerm, Yves Beguin, Natacha Maillard, jean-baptiste Mear, Emilie Chalayer, and Jerome Cornillon

Abstract

We report the results from a multicentre retrospective study of 220 adult patients who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT) for therapy-related acute myeloid leukemia (t-AML). Median age at t-AML diagnosis was 56 years, with a prior history of haematological (45%) or gynaecological neoplasia (37%). Median time from cytotoxic exposure to t-AML diagnosis was 54.7 months. At transplant, around 20% of patients had measurable residual disease and 3% of patients were not in complete remission. The median follow-up was 21.4 months (Q1-Q3, 5.9–52.8). At 12 months, overall survival (OS), event-free survival (EFS), and graft-versus-host-disease (GVHD)-free-relapse-free survival (GRFS) were 60.7% (95% CI 54.6–67.5), 52.8% (95% CI 46.5–68.4), and 44.1% (95% CI 37.6–51.8), respectively. At 5 years, OS, EFS, and GRFS were 44.1% (95% CI 37.4–52.1), 40.4% (95% CI 33.9–48.1), and 35.3% (95% CI 28.8–43.3), respectively. At last follow-up, 44% of patients were in complete remission (n = 96) and transplant-related mortality accounted for 39% of all deaths (n = 119). Multivariable analysis revealed that uncontrolled t-AML at transplant was associated with lower EFS (HR 1.94, 95% CI 1.0-3.7, p = 0.041). In conclusion, alloHSCT for t-AML shows encouraging results and offers additional opportunity with the emergence of novel pre-graft therapies.

Published
2023

29. On behalf of the SFGM-TC: prophylactic donor lymphocyte infusion in patients treated with allogeneic stem-cell transplantation for high-risk myelodysplastic syndrome and acute myeloid leukemia

Author

Charles Guisnel, Luciane Schirmer, Stéphane Morisset, Marie Robin, Hélène Labussière-Wallet, Rémy Duléry, Patrice Ceballos, Edouard Forcade, Stéphanie Nguyen, Xavier Poiré, Johan Maertens, Sylvain Chantepie, Patrice Chevallier, Etienne Daguindau, Alban Villate, Amandine Charbonnier, Cristina Castilla-Llorente, Nathalie Contentin, ANNE Huynh, Ibrahim Yakoub-Agha, claude eric bulabois, Marie-Thérèse Rubio, and Maud D'Aveni

Subjects
Hematology, General Medicine
Abstract

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Unfortunately, it is still associated with a significant risk of relapse due to mechanisms of escape from the control of alloreactive T cells. Repetitive adjuvant donor lymphocyte infusions (DLI), termed prophylactic DLI (proDLI), as an effective strategy in preventing relapse is still debated. Methods: We performed a retrospective multicenter study to evaluate the efficacy of proDLI in allografted AML and MDS. We identified 56 patients treated with proDLI (DLI planned in full chimeras without any sign of disease relapse) and matched them to 167 patients in control group, (DLI performed for mixed chimerism or positive minimal residual disease) based on similar age, initial disease, cytogenetic prognosis, and conditioning intensity. Results: In univariate analysis, the incidence of severe aGVHD at 100 days and incidence of all grades of chronic GVHD 1 year after allo-HSCT were similar in the two groups. We also observed a trend of higher 3-year RI (52.61% [95% confidence interval 25.99-79.23]) in the proDLI group versus the control group (29.31% [20.28-38.34], p=0.067). However, 3-year overall survival (p=0.892), progression-free survival (p=0.239), and non-relapse mortality (p=0.343) were similar between the two groups. In multivariate analysis, the only factor influencing overall and progression-free survival was anti-thymocyte globulin administration during the conditioning regimen. Discussion/Conclusion: The proDLI strategy had an acceptable toxicity profile but did not improve patient outcomes compared to the pre-emptive strategy.

Published
2023

31. CAR T-cell therapy in primary central nervous system lymphoma: the clinical experience of the French LOC network

Author

Marion Alcantara, Caroline Houillier, Marie Blonski, Marie-Thérèse Rubio, Lise Willems, Agathe Waultier Rascalou, Magali Le Garff-Tavernier, Karim Maloum, Clotilde Bravetti, Laetitia Souchet, Damien Roos-Weil, Véronique Morel, Madalina Uzunov, Carole Metz, Meriem Dhib-Charfi, Stéphanie Nguyen, Natalia Shor, Dimitri Psimaras, Nicolas Weiss, Nathalie Jacque, Silvia Solorzano, Nicolas Gauthier, Marie Le Cann, Françoise Norol, Carole Soussain, and Sylvain Choquet

Subjects
Central Nervous System, Male, Immunology, Cell Biology, Hematology, Middle Aged, Immunotherapy, Adoptive, Survival Analysis, Biochemistry, Central Nervous System Neoplasms, Cohort Studies, Humans, Female, France, Lymphoma, Large B-Cell, Diffuse, Letter to Blood, Aged
Published
2022

32. Antibody response after 2 and 3 doses of SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic cell transplant recipients

Author

Patrice Chevallier, Cristina Castilla-Llorente, Anne Thiebaut-Bertand, Stéphanie Nguyen, Maud D'Aveni, Rabah Redjoul, Mathieu Leclerc, Magalie Joris, Alexis Maillard, Hélène Labussière-Wallet, Carmen Botella-Garcia, Michael Loschi, Marion Klemencie, Sylvain Chantepie, Ana Berceanu, Amandine Le Bourgeois, Sylvie François, Anne Huynh, Tony Marchand, Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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 hospitalier universitaire de Nantes (CHU Nantes), 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 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), Service d'Hématologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d’Hématologie Clinique [Rennes], CHU Pontchaillou [Rennes], 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, CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Amiens-Picardie, Institut Gustave Roussy (IGR), Département d'hématologie [Gustave Roussy], and Centre Hospitalier Universitaire [Grenoble] (CHU)

Subjects
Male, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Dose-Response Relationship, Immunologic, Immunization, Secondary, Antibodies, Viral, Biochemistry, Immunocompromised Host, Immunogenicity, Vaccine, Humans, Medicine, Letter to Blood, BNT162 Vaccine, Aged, Retrospective Studies, Messenger RNA, Hematopoietic cell, SARS-CoV-2, business.industry, Hematopoietic Stem Cell Transplantation, COVID-19, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Cell Biology, Hematology, Middle Aged, Allografts, Virology, Antibody response, Multivariate Analysis, Female, business, 2019-nCoV Vaccine mRNA-1273
Abstract

International audience; Three reports address the protection of the vulnerable population of patients with hematologic malignancies in the face of the ongoing COVID pandemic. The reports suggest that some patients who fail to mount a B-cell response to vaccine may nevertheless have protective T cell responses. As a group, these reports suggest that patients should continue to be immunized with additional doses to attempt to improve immune response but that they need to maintain the precautions recommended for the unvaccinated.

Published
2022

33. Hematopoietic stem cell transplantation for DLBCL: a report from the European Society for Blood and Marrow Transplantation on more than 40,000 patients over 32 years

Author

Philipp Berning, Mathilde Fekom, Maud Ngoya, Anthony H. Goldstone, Peter Dreger, Silvia Montoto, Hervé Finel, Evgenii Shumilov, Patrice Chevallier, Didier Blaise, Tim Strüssmann, Ben Carpenter, Edouard Forcade, Cristina Castilla-Llorente, Marek Trneny, Hervé Ghesquieres, Saveria Capria, Catherine Thieblemont, Igor Wolfgang Blau, Ellen Meijer, Annoek E. C. Broers, Anne Huynh, Denis Caillot, Wolf Rösler, Stephanie Nguyen Quoc, Jörg Bittenbring, Arnon Nagler, Jacques-Emmanuel Galimard, Bertram Glass, Anna Sureda, and Norbert Schmitz

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990–1994) to 58 years (2015–2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990–1994) to 54 (2015–2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015–2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990–1994) to 70% (2015–2021), p 40,000 transplants, providing insights for evaluating emerging DLBCL therapies.

Published
2024
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34. Immunomonitoring of patients treated with CAR-T cells for hematological malignancy: guidelines from the CARTi group and the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)

Author

Pauline Varlet, Christophe Ferrand, Marie-Thérèse Rubio, Claude Lemarie, Marina Deschamps, Alexis Cuffel, Amélie Guihot, Florence Morin, Ibrahim Yakoub-Agha, Caroline Ballot, Guillaume Martinroche, Vincent Allain, Sophie Servais, Jacques Foguenne, Kathleen Schmit, Federico Simonetta, Anne Huynh, Sophie Caillat Zucman, Edouard Forcade, Jean-Baptiste Latouche, Stéphanie Nguyen, 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), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Etablissement Français du Sang Hauts-de-France - Normandie (EFS Hauts-de-France - Normandie), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Bordeaux [Bordeaux], 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 Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Hôpital de la Conception - APHM] (CIC), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Université de Genève = University of Geneva (UNIGE), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Bone marrow transplantation, business.industry, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Context (language use), Hematology, General Medicine, Immunotherapy, Cell therapy, Clinical trial, Apheresis, Immune system, Internal medicine, Toxicity, medicine, Radiology, Nuclear Medicine and imaging, business, ComputingMilieux_MISCELLANEOUS
Abstract

CAR-T cells represent a new anti-tumor immunotherapy which has shown its clinical efficacy in B-cell malignancies. The results of clinical trials carried out in this context have shown that certain immunological characteristics of patients before (at the time of apheresis) and after the administration of the treatment, or of the CAR-T cells themselves, are correlated with the response to the treatment or to its toxicity. However, to date, there are no recommendations on the immunological monitoring of patients treated in real life. The objectives of this workshop were to determine, based on data from the literature and the experience of the centers, the immunological analyses to be carried out in patients treated with CAR-T cells. The recommendations relate to the characterization of the patient's immune cells at the time of apheresis, the characterization of the injected CAR-T cells, as well as the monitoring of the CAR-T cells and other parameters of immune reconstitution in the patient after administration of the treatment. Harmonization of practices will allow clinical-biological correlation studies to be carried out in patients treated in real life with the aim of identifying factors predictive of response and toxicity. Such data could have a major medico-economic impact by making it possible to identify the patients who will optimally benefit from these expensive treatments.

Published
2021

35. Pulmonary Alveolar Proteinosis After Allogeneic Hematopoietic Stem-Cell Transplantation in Adults

Author

Jean-François Bernaudin, Hélène Salvator, Natacha Maillard, Marie-Thérèse Rubio, Sarah Guenounou, Simona Sestili, Colas Tcherakian, Louise Bondeelle, Laetitia Souchet, Emilie Catherinot, Céline Goyard, Véronique Meignin, Solène Evrard, Elisabeth Longchampt, Marie-Laure Chabi-Charvillat, Eolia Brissot, Anne Fajac, Stéphanie Nguyen, Serge Milin, Anne Bergeron, Louis-Jean Couderc, Claire Givel, Alexandre Chabrol, and Marie Robin

Subjects
Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, business.industry, medicine.medical_treatment, medicine, Hematopoietic stem cell transplantation, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine, Pulmonary alveolar proteinosis, medicine.disease, business
Published
2021

36. DESCAR-T, le registre national des patients traités par CAR-T Cells

Author

Florence Broussais, Jacques Olivier Bay, Nicolas Boissel, André Baruchel, Bertrand Arnulf, Franck Morschhauser, Marie Robin, Gabrielle Roth Guepin, Philippe Moreau, Virginie Gandemer, Salomon Manier, Thibaut Leguay, Stéphanie Nguyen Quoc, Alexia Schwartzmann, Roch Houot, and Steven Le Gouill

Subjects
Cancer Research, Oncology, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine
Published
2021

39. One-month humoral response following two or three doses of mRNA Covid-19 vaccines as primary vaccination in specific populations in France: first results from the ANRS0001S COV-POPART cohort

Author

Loubet, Paul, Wittkop, Linda, Ninove, Laetitia, Chalouni, Mathieu, Barrou, Benoit, Blay, Jean-Yves, Hourmant, Maryvonne, Thouvenot, Eric, Laville, Martine, Laviolle, Bruno, Lelievre, Jean-Daniel, Morel, Jacques, Quoc, Stéphanie Nguyen, Spano, Jean-Philippe, Terrier, Benjamin, Thiebaut, Anne, Viallard, Jean-Francois, Vrtovsnik, François, Circosta, Sophie, Esterle, Laure, Levier, Axel, Vanhems, Philippe, Tartour, Eric, Parfait, Beatrice, de Lamballerie, Xavier, Launay, Odile, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Virulence Bactérienne et Infections Chroniques (VBIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- 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)-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), 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 Bordeaux [Bordeaux], CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre Léon Bérard [Lyon], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, UNICANCER, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Grenoble, Hôpital Haut-Lévêque [CHU Bordeaux], Université de Bordeaux (UB), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Fédération Île-de-France de Recherche sur l'Environnement (FIRE), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-AgroParisTech-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris Cité (UPCité), Essais Thérapeutiques et Maladies Infectieuses, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS - Maladies infectieuses émergentes (ANRS - MIE), Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Edouard Herriot [CHU - HCL], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), ANRS0001S COV-POPART study group, MORNET, Dominique, Association Francaise d'Etudes et de Recherches sur l'Obesite, Partenaires INRAE, ANRS|Maladies infectieuses émergentes (ANRS|MIE), Vaccine Research Institute [Créteil, France] (VRI), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV] Life Sciences [q-bio], Efficacy, Specific populations, [SDV]Life Sciences [q-bio], COVID-19, Humoral, Immunocompromised, Immunogenicity
Abstract

International audience; Objectives - We aimed to investigate the 1-month humoral response to two or three doses of a messenger RNA coronavirus disease 2019 (COVID-19) vaccine as a primary vaccination regimen in specific populations compared with that in healthy adults. Methods - Agence Nationale Recherche contre le Sida (ANRS)0001S-COV-POPART (NCT04824651) is a French nation-wide, multi-centre, prospective, observational cohort study assessing the immune response to COVID-19 vaccines routinely administered to 11 sub-groups of patients with chronic conditions and two control groups. Patients and controls who received at least two vaccine doses and whose results 1 month after the second dose were available were included. The humoral response was assessed 1 month after the first, second and third doses (if applicable) based on the percentage of responders (positive for anti-Spike severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] IgG antibodies), geometric means of anti-Spike SARS-CoV-2 IgG antibodies (enzyme-linked immunosorbent assay) and proportion of participants with anti-SARS-CoV-2-specific neutralizing antibodies (in vitro neutralization assay for the original SARS-CoV-2 strain). All analyses were centralized. Results - We included 4091 participants in this analysis: 2979 participants from specific sub-populations and 1112 controls. Only 522 (17.5%) participants from the specific populations received three doses as a primary vaccination regimen. Patients living with human immunodeficiency virus, cancer and diabetes had high percentages of responders after two doses, whereas patients with solid organ transplants, allogeneic hematopoietic stem cell transplants and hypogammaglobulinaemia had the lowest percentage of responders (35.9% [95% CI, 29.2-43.0], 57.4% [95% CI, 48.1-66.3] and 77.1% [95% CI, 65.6-86.3], respectively). In those who received the third dose, the percentage of responders reached 54.2% (95% CI, 42.9-65.2) (vs. 32.3% [95% CI, 16.7-51.4] after 2 doses) among those with solid organ transplants and 73.9% (95% CI, 58.9-85.7) (vs. 56.1% [95% CI, 46.2-65.7] after 2 doses) among those with hematopoietic stem cell transplants. Similar results were found with anti-SARS-CoV-2-specific neutralizing antibodies. Conclusions - A lower humoral response to COVID-19 vaccines was observed in the specific populations compared with that in the controls. The third dose of this vaccine in the primary regimen had a positive effect on the percentages of patients who developed anti-Spike IgG antibodies and specific neutralizing antibodies.

Published
2022

40. Outcomes after allogeneic hematopoietic stem cell transplantation for adults with primary mediastinal B cell lymphoma: a SFGM-TC and LYSA study

Author

Baptiste Le Calvez, Benoit Tessoullin, Loïc Renaud, Carmen Botella-Garcia, Micha Srour, Steven Le Gouill, Gaelle Guillerm, Rémy Gressin, Stéphanie Nguyen Quoc, Sabine Furst, Adrien Chauchet, David Sibon, Philippe Lewalle, Xavier Poiré, Natacha Maillard, Alban Villate, Michael Loschi, Jérôme Paillassa, Yves Beguin, Rémy Dulery, Jean-Jacques Tudesq, Amandine Fayard, Marie C. Béné, Vincent Camus, Patrice Chevallier, Amandine Le Bourgeois, Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez [Lille], CHU Lille, Université de Lille, Institut Curie [Paris], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Jules Bordet [Bruxelles], Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Université libre de Bruxelles (ULB), Cliniques universitaires St Luc [Bruxelles], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Universitaire de Liège (CHU-Liège), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Fédérations hospitalo-universitaires Grand Ouest Acute Leukemia [Angers] (FHU GOAL), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Laboratoire d'Hematologie [CHU Nantes], and Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)

Subjects
Adult, Lymphoma, B-Cell, Oncology, Recurrence, [SDV]Life Sciences [q-bio], Remission Induction, Hematopoietic Stem Cell Transplantation, Humans, Graft vs Host Disease, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine, Retrospective Studies
Abstract

Background: Despite therapeutic progress, 10 to 30% of adult patients with primary mediastinal B cell lymphoma (PMBCL) are primary refractory or experience early relapse (R/R). Allogeneic stem cell transplantation (allo-HSCT) thus remains a potentially curative option in this setting. Material and Methods: In this multicenter retrospective study, the outcomes of 33 French and Belgian adult patients allo-transplanted for R/R PMBCL between January 1999 and December 2018, were examined. Results: At allo-HSCT time, patients had received a median of 3 treatment lines, 50% of them were in complete response, 40% in partial response and 10% had a progressive disease. Forty-two percent of the donors were siblings and 39% matched related. The median follow-up for alive patients was 78 months (3.5-157). Considering the whole cohort, 2-year overall survival (OS), progression free survival (PFS) and graft-versus-host disease-free/relapse-free survival (GRFS) were 48% (95%CI: 33-70), 47% (95%CI: 33-68) and 38.5% (95%CI: 25-60) respectively. Cumulative incidence of relapse and non-relapse mortality rates were respectively 34% (95%CI: 18-50) and 18% (95%CI: 7-34). Disease status at transplant was the only factor predicting survivals, patients with progressive disease showing significant lower 2-year PFS (HR: 6.12, 95%CI: 1.32-28.31, p = 0.02) and OS (HR: 7.04, 95%CI: 1.52-32.75, p = 0.013). A plateau was observed for OS and PFS after 4 years with 10 patients alive after this date, suggesting that almost one third of the patients effectively salvaged and undergoing allo-SCT could be cured. Conclusion: This study indicates that allo-HSCT is a valid therapeutic option for R/R PMBCL, providing durable remissions.

Published
2022

41. Faecal microbiota transplantation to prevent complications after allogeneic stem cell transplantation for haematological malignancies: a study protocol for a randomised controlled phase-II trial (the FMT-allo study)

Author

Aurore Dougé, Aurélie Ravinet, Alexandrine Corriger, Aurélie Cabrespine, Mathieu Wasiak, Bruno Pereira, Harry Sokol, Stéphanie Nguyen, and Jacques-Olivier Bay

Subjects
General Medicine
Abstract

IntroductionAllogeneic haematopoietic stem-cell transplantation (allo-HSCT) is a major treatment for many haematological malignancies. The procedure has a good success rate but high transplant-related toxicity (TRM). TRM is mostly related to graft-versus-host disease (GvHD) and infectious complications. Alterations of the intestinal microbiota plays a major role in the development of allo-HSCT complications. The gut microbiota could be restored by faecal microbiota transplantation (FMT). However, there are no published randomised studies assessing the efficacy of FMT for GvHD prophylaxis.Methods and analysisThis prospective, open-label, multi-centre, parallel-group, randomised phase-II clinical trial has been designed to assess the effect of FMT on toxicity in patients treated with myeloablative allo-HSCT for haematological malignancy. Based on Fleming’s single-stage sample size estimation procedure, the design plans to include 60 male and female patients aged 18 or over per arm, to be randomly assigned to two groups, one with and one without (control group) FMT. The primary endpoint is GvHD-free relapse-free survival rate at 1 year after allo-HSCT. Secondary endpoints are outcome measures of the impact of FMT on allo-HSCT-related morbidity and mortality (overall survival and progression-free survival at 1 and 2 years, haematological parameters, infectious complications, tolerance and safety of FMT). The primary endpoint will be evaluated according to assumptions of the single-stage Fleming design, compared between groups by a log-rank test and further investigated in a multivariate marginal structural Cox model taking into account centre effect. The proportional-hazard hypothesis will be verified using Schoenfeld’s test and by plotting residuals.Ethics and disseminationThe local institutional review board (CPP Sud-Est II, France) issued approval on 27 January 2021. The French national authorities issued approval on 15 April 2021. The outcome of the study will be disseminated via peer-reviewed publications and at congresses.Trial registration numberNCT04935684.

Published
2023

42. Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients

Author

Xavier Thomas, Lilia Boucinha, Christian Recher, Anne-Sophie Michallet, Sophie Ducastelle-Lepretre, Mauricette Michallet, Stéphanie Nguyen, Clément Rocher, Pierre Peterlin, Etienne Paubelle, Florent Malard, Suzanne Tavitian, Colombe Saillard, Marie-Virginie Larcher, Sarah Bertoli, Evelyne D'incan-Corda, Ollivier Legrand, Patrice Chevallier, Emilie Plantamura, Joël Doré, Anne Vekhoff, Simona Lapusan, Jerome Rey, Lila Gilis, Mohamad Mohty, Cyrielle Gasc, Françoise Isnard, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), 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), Centre Léon Bérard [Lyon], Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), MaaT Pharma [Lyon], MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Project: 788191,Homo.symbiosus, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Antibiotics, General Physics and Astronomy, Gut flora, Feces, 0302 clinical medicine, fluids and secretions, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, education.field_of_study, Multidisciplinary, biology, Myeloid leukemia, Fecal Microbiota Transplantation, Middle Aged, Anti-Bacterial Agents, 3. Good health, Leukemia, Treatment Outcome, Leukemia, Myeloid, 030220 oncology & carcinogenesis, Acute Disease, Female, Adult, medicine.drug_class, Science, Population, Transplantation, Autologous, digestive system, Article, Phase II trials, Acute myeloid leukaemia, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, medicine, Humans, education, Aged, Bacteria, business.industry, Induction chemotherapy, General Chemistry, biology.organism_classification, medicine.disease, Gastrointestinal Microbiome, Transplantation, 030104 developmental biology, Immunology, Dysbiosis, business
Abstract

Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523). The co-primary outcomes of the study are to evaluate the efficacy of AFMT in dysbiosis correction and multidrug-resistant bacteria eradication. The main secondary outcomes are to define a dysbiosis biosignature, to evaluate the effect of dysbiosis correction on patient clinical status, to assess the short and mid-term safety of AFMT in this immunocompromised population, and to evaluate the feasibility of the AFMT procedure and acceptability by the patient. Intensive induction chemotherapy induces a dramatic decrease of α-diversity indices, and a microbial dysbiosis with a significant shift of the microbial communities and domination of pro-inflammatory families. After AFMT treatment, α-diversity indices return to their initial mean levels and the similarity index shows the restoration of microbial communities. The trial meets pre-specified endpoints. AFMT appears to be safe and may be effective for gut microbiota restoration in AML patients receiving intensive chemotherapy and antibiotics, with an excellent gut microbiota reconstruction based on both richness and diversity indices at the species level., The combination of chemotherapy and broad-spectrum antibiotics induces gut microbiota (GM) dysbiosis in acute myeloid leukaemia (AML) leading to additional complications. Here, the authors report the efficacy in GM restoration and safety of autologous faecal microbiota transfer in treated AML patients in a phase II clinical trial.

Published
2021

43. Role and Modulation of NK Cells in Multiple Myeloma

Author

Stéphanie Nguyen, Adele Dhuyser, and Marie-Thérèse Rubio

Subjects
medicine.drug_class, medicine.medical_treatment, lcsh:R, lcsh:Medicine, NK cells, Immunotherapy, CD38, Biology, immunomodulation, Monoclonal antibody, Chimeric antigen receptor, 03 medical and health sciences, myeloma, 0302 clinical medicine, Immune system, Antigen, 030220 oncology & carcinogenesis, Cancer research, medicine, Cytotoxic T cell, immunotherapy, cell therapy, Receptor, 030215 immunology
Abstract

Myeloma tumor cells are particularly dependent on their microenvironment and sensitive to cellular antitumor immune response, including natural killer (NK) cells. These later are essential innate lymphocytes implicated in the control of viral infections and cancers. Their cytotoxic activity is regulated by a balance between activating and inhibitory signals resulting from the complex interaction of surface receptors and their respective ligands. Myeloma disease evolution is associated with a progressive alteration of NK cell number, phenotype and cytotoxic functions. We review here the different therapeutic approaches that could restore or enhance NK cell functions in multiple myeloma. First, conventional treatments (immunomodulatory drugs-IMids and proteasome inhibitors) can enhance NK killing of tumor cells by modulating the expression of NK receptors and their corresponding ligands on NK and myeloma cells, respectively. Because of their ability to kill by antibody-dependent cell cytotoxicity, NK cells are important effectors involved in the efficacy of anti-myeloma monoclonal antibodies targeting the tumor antigens CD38, CS1 or BCMA. These complementary mechanisms support the more recent therapeutic combination of IMids or proteasome inhibitors to monoclonal antibodies. We finally discuss the ongoing development of new NK cell-based immunotherapies, such as ex vivo expanded killer cell immunoglobulin-like receptors (KIR)-mismatched NK cells, chimeric antigen receptors (CAR)-NK cells, check point and KIR inhibitors.

Published
2021

44. Hemi-Nikaidoh: Partial Aortic Root Translocation and Posterior Left Ventricular Outflow Tract Plasty

Author

Emile Bacha, MD, Stephanie Nguyen, MD, David Blitzer, MD, and Maroun Yammine, MD

Subjects
Surgery, RD1-811, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Among repairs for ventriculoarterial discordance, ventricular septal defect, and pulmonary stenosis, aortic root translocation (Nikaidoh operation) offers the most anatomic result. With a diminutive pulmonary annulus or hypoplastic left ventricular outflow tract, the distance gained posteriorly with aortic translocation is negligible. We developed the “hemi-Nikaidoh” procedure as an alternative. Geometric shift is achieved by mobilizing the anterior two-thirds of the aortic root, and posterior aortic translocation is performed by plicating the left ventricular outflow tract without dividing the conus. The right ventricular outflow tract is reconstructed with an orthotopic conduit. Herein, we describe the hemi-Nikaidoh operation.

Published
2024
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45. One-month humoral response following two or three doses of messenger RNA coronavirus disease 2019 vaccines as primary vaccination in specific populations in France: first results from the Agence Nationale Recherche contre le Sida (ANRS)0001S COV-POPART cohort

Author

Paul Loubet, Linda Wittkop, Laetitia Ninove, Mathieu Chalouni, Benoit Barrou, Jean-Yves Blay, Maryvonne Hourmant, Eric Thouvenot, Martine Laville, Bruno Laviolle, Jean-Daniel Lelievre, Jacques Morel, Stéphanie Nguyen Quoc, Jean-Philippe Spano, Benjamin Terrier, Anne Thiebaut, Jean-Francois Viallard, François Vrtovsnik, Sophie Circosta, Laure Esterle, Axel Levier, Philippe Vanhems, Eric Tartour, Beatrice Parfait, Xavier de Lamballerie, and Odile Launay

Subjects
Microbiology (medical), Infectious Diseases, General Medicine
Abstract

We aimed to investigate the 1-month humoral response to two or three doses of a messenger RNA coronavirus disease 2019 (COVID-19) vaccine as a primary vaccination regimen in specific populations compared with that in healthy adults.Agence Nationale Recherche contre le Sida (ANRS)0001S-COV-POPART (NCT04824651) is a French nation-wide, multi-centre, prospective, observational cohort study assessing the immune response to COVID-19 vaccines routinely administered to 11 sub-groups of patients with chronic conditions and two control groups. Patients and controls who received at least two vaccine doses and whose results 1 month after the second dose were available were included. The humoral response was assessed 1 month after the first, second and third doses (if applicable) based on the percentage of responders (positive for anti-Spike severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] IgG antibodies), geometric means of anti-Spike SARS-CoV-2 IgG antibodies (enzyme-linked immunosorbent assay) and proportion of participants with anti-SARS-CoV-2-specific neutralizing antibodies (in vitro neutralization assay for the original SARS-CoV-2 strain). All analyses were centralized.We included 4091 participants in this analysis: 2979 participants from specific sub-populations and 1112 controls. Only 522 (17.5%) participants from the specific populations received three doses as a primary vaccination regimen. Patients living with human immunodeficiency virus, cancer and diabetes had high percentages of responders after two doses, whereas patients with solid organ transplants, allogeneic hematopoietic stem cell transplants and hypogammaglobulinaemia had the lowest percentage of responders (35.9% [95% CI, 29.2-43.0], 57.4% [95% CI, 48.1-66.3] and 77.1% [95% CI, 65.6-86.3], respectively). In those who received the third dose, the percentage of responders reached 54.2% (95% CI, 42.9-65.2) (vs. 32.3% [95% CI, 16.7-51.4] after 2 doses) among those with solid organ transplants and 73.9% (95% CI, 58.9-85.7) (vs. 56.1% [95% CI, 46.2-65.7] after 2 doses) among those with hematopoietic stem cell transplants. Similar results were found with anti-SARS-CoV-2-specific neutralizing antibodies.A lower humoral response to COVID-19 vaccines was observed in the specific populations compared with that in the controls. The third dose of this vaccine in the primary regimen had a positive effect on the percentages of patients who developed anti-Spike IgG antibodies and specific neutralizing antibodies.

Published
2023

46. Identification of Prognostic Factors in Post-Transplant Lymphoproliferative Disorders

Author

Choquet, Sylvain, Bruneel, Marie-France Mamzer, Hermine, Olivier, Porcher, Raphaël, Quoc, Stephanie Nguyen, Davi, Frédéric, Charlotte, Frédéric, Dorent, Richard, Barrou, Benoit, Vernant, Jean-Paul, Raphael, Martine, Levy, Vincent, Leblond, Véronique, Schlag, P. M., editor, Senn, H.-J., editor, Diehl, V., editor, Parkin, D. M., editor, Rajewsky, M. F., editor, Rubens, R., editor, Wannenmacher, M., editor, Rentchnik, P., editor, Oertel, Stephan H., editor, and Riess, Hanno, editor

Published
2002
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47. Venoarterial Extracorporeal Membrane Oxygenation Support Rescue of Obstructive Shock Caused by Bulky Compressive Mediastinal Cancer

Author

Matthieu Schmidt, Nicolas Bréchot, Alain Combes, Stéphanie Nguyen, Guillaume Hékimian, Patricia Villie, Guillaume Lebreton, Simon Bourcier, Charles-Edouard Luyt, and Pierre Demondion

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Adolescent, Critical Illness, medicine.medical_treatment, Treatment outcome, Shock, Cardiogenic, Critical Care and Intensive Care Medicine, Mediastinal Neoplasms, Risk Assessment, Sampling Studies, Young Adult, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Internal medicine, Extracorporeal membrane oxygenation, medicine, Humans, Retrospective Studies, business.industry, Follow up studies, Cancer, 030208 emergency & critical care medicine, medicine.disease, Airway Obstruction, Survival Rate, Intensive Care Units, Treatment Outcome, 030228 respiratory system, Obstructive shock, Shock (circulatory), Cardiology, Female, medicine.symptom, Tomography, X-Ray Computed, business, Follow-Up Studies
Published
2020

48. Hematopoietic stem cell transplantation for acute lymphoblastic leukemia: why do adolescents and young adults outcomes differ from those of children? A retrospective study on behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)

Author

Audrey Grain, Fanny Rialland, Patrice Chevallier, Nicolas Blin, Jean-Hugues Dalle, Gérard Michel, Nathalie Dhédin, Régis Peffault de Latour, Cécile Pochon, Ibrahim Yakoub-Agha, Yves Bertrand, Anne Sirvent, Charlotte Jubert, Edouard Forcade, Ana Berceanu, Virginie Gandemer, Pascale Schneider, Jacques-Olivier Bay, Pierre-Simon Rohrlich, Eolia Brissot, Catherine Paillard, Dominique Plantaz, Stéphanie Nguyen Quoc, Fanny Gonzales, Natacha Maillard, Lucie Planche, Andre Baruchel, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Robert Debré, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and None

Subjects
MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Adolescent, Cancer Research, MESH: Humans, MESH: Child, Preschool, MESH: Graft vs Host Disease, Hematopoietic stem cell transplantation, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Acute lymphoblastic leukemia, Graft versus host disease, MESH: Infant, humanities, Adolescents and young adults, Oncology, MESH: Young Adult, hemic and lymphatic diseases, MESH: Child, MESH: Hematopoietic Stem Cell Transplantation
Abstract

International audience; Purpose: In the acute lymphoblastic leukemia (ALL) landscape, adolescents and young adults (AYA) often present high-risk diseases and increased chemotherapy-related toxicity. Studies analyzing the outcomes of AYA after hematopoietic stem cell transplantation (HSCT) are scarce. Our study aimed to compare the outcomes of children and AYA with ALL after HSCT and to determine the factors influencing potential differences.Method: 891 patients, from the SFGM-TC registry, aged between 1 and 25 years who received HSCT between 2005 and 2012 were included. The outcomes of AYA were compared to the ones of their younger counterparts.Results: Five-year OS and GRFS were lower in AYA: 53.1% versus 64% and 36% versus 47% (p = 0.0012 and p = 0.007, respectively). WhileCIR was similar in both groups, 5 year-treatment related mortality was higher in AYA: 19% versus 13% (p = 0.04). The lower GRFS in AYA was mainly explained by a higher chronic graft versus host disease (cGvHD) incidence: 32% versus 19% (p < 0.001). Use of peripheral blood stem cells and use of anti-thymoglobulin appeared to be the main factors impacting cGvHD occurrence in AYA.Conclusion: AYA have worse outcomes than children after HSCT for ALL because of a greater risk of TRM due to cGvHD. HSCT practices should be questioned in this population.Keywords: Acute lymphoblastic leukemia; Adolescents and young adults; Graft versus host disease; Hematopoietic stem cell transplantation.

Published
2022

49. Transgender health and medicine - Are radiological devices prepared?

Author

Simon Matoori, Ricardo Donners, David Garcia Nuñez, Stéphanie Nguyen-Duong, Corine Riopel, Melanie Baumgartner, Elisabeth Sartoretti, Thomas Sartoretti, Sabine Sartoretti-Schefer, Tanja Volm, Johannes M. Fröhlich, Rosemarie Forstner, Dow-Mu Koh, and Andreas Gutzeit

Subjects
Male, Radiography, Surveys and Questionnaires, Gender Identity, Humans, Radiology, Nuclear Medicine and imaging, Female, General Medicine, Radiology, Transgender Persons
Abstract

To determine if radiological hard- and software offers options beyond the binary female / male classification.We surveyed thirteen radiological hardware and six radiological software vendors about the options to enter patient gender.Six of thirteen hardware and five of six software vendors replied to our inquiry. All vendors except one offered a third option in addition to male / female.We found that most hard- and software systems provide with a third option for patient gender. These systems allow radiology personnel to accurately document patient gender in the medical record and contribute to an inclusive patient experience in the radiology department. Registering the biological sex in addition to gender may further improve medical care.

Published
2022

50. Reduced intensity versus non-myeloablative conditioning regimen for haploidentical transplantation and post-transplantation cyclophosphamide in complete remission acute myeloid leukemia: a study from the ALWP of the EBMT

Author

Raynier Devillier, Jacques-Emmanuel Galimard, Myriam Labopin, Didier Blaise, Anna Maria Raiola, Jiri Pavlu, Luca Castagna, Gerard Socié, Yves Chalandon, Massimo Martino, Friedrich Stölzel, Gesine Bug, Benedetto Bruno, Radovan Vrhovac, Amandine Charbonnier, Attilio Olivieri, Jacques-Olivier Bay, Herrera Arroyo, Ibrahim Yakoub-Agha, Daniele Avenoso, Andreas Neubauer, Stéphanie Nguyen, Edouard Forcade, Eolia Brissot, Bipin Savani, Arnon Nagler, and Mohamad Mohty

Subjects
Myeloid, Transplantation, Aged, Busulfan, Cyclophosphamide, Humans, Recurrence, Retrospective Studies, Transplantation Conditioning, Transplantation, Haploidentical, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute, Leukemia, reduced intensity, non-myeloablative, conditioning, acute myeloid leukemia, Hematology, Acute, Haploidentical
Abstract

The optimal conditioning regimen prior haploidentical stem cell transplantation (Haplo-SCT) with post transplantation cyclophosphamide (PT-Cy) for acute myeloid leukemia (AML) remains unknown. A non-myeloablative conditioning (NMAC) regimen (cyclophosphamide + fludarabine + TBI 2 Gy [CyFluTBI]) is a safe approach, but relapse incidence remains high in this setting. Alternatively, a reduced intensity conditioning (RIC) regimen combining thiotepa and reduced-dose busulfan with fludarabine (TBF) may decrease AML relapse. However, an excess of toxicity may counterbalance this potential benefit. We retrospectively compared CyFluTBI vs. TBF in CR AML patients who underwent Haplo-SCT with PT-Cy, in two different populations based on age. We analyzed 490 patients. In patients aged

Published
2022

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