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115 results on '"Amandine Le Bourgeois"'

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. Pre-graft vaccination or infection do not decrease COVID-19 infections in recipients of allogeneic stem cell transplantation vaccinated and/or protected by immunotherapy after transplant

Author

Valentin Letailleur, Amandine Le Bourgeois, Thierry Guillaume, Alice Garnier, Pierre Peterlin, Maxime Jullien, Chloe Antier, Marie-Christine Béné, and Patrice Chevallier

Subjects
COVID-19, allogeneic, vaccine, infection, BNT162b2, mRNA-1273, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract

The impact of pre-graft COVID-19 vaccinations in donor or recipient as well as pre-graft infection has been studied in 157 adults having received allogeneic stem cell transplantation (Allo-SCT) for various hematological diseases during the delta/omicron waves. We showed here that pre-Allo-SCT COVID-19 vaccination and/or infection do not provide more protection in patients receiving vaccine, immunotherapy or both after transplant. COVID-19 vaccination is and remains of crucial importance after Allo-SCT, reinforcing the recommendation to start COVID-19 vaccination as soon as the third month following the transplant.

Published
2024
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3. Assessment of monocytic‐myeloid‐derived suppressive cells (M‐MDSC) before and after allogeneic hematopoietic stem cell transplantation in acute leukemia patients

Author

Pierre Peterlin, Marie C. Béné, Maxime Jullien, Thierry Guillaume, Amandine Le Bourgeois, Alice Garnier, Camille Debord, Marion Eveillard, and Patrice Chevallier

Subjects
ALL, Allo‐HSCT, AML, diagnosis, MDSC, monocytes, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract In this monocentric prospective study, the influence on long‐term outcomes of peripheral blood levels of monocytic‐myeloid‐derived suppressive cells (M‐MDSC) was investigated in 56 patients with acute leukemia (myeloid n = 47; lymphoid n = 9) before and after (Days+60/+90) allogeneic hematopoietic stem cell transplantation (Allo‐HSCT). A risk of relapse was found to be associated with a level of pregraft M‐MDSC above 1.4% by ROC curve analysis. In multivariate analysis, this threshold retained a strong statistical significance (HR: 5.94 [2.09–16.87], p = 0.001). Considering only the group of patients who were in complete remission prior to Allo‐HSCT (n = 44), a significant prediction of relapse was found to be associated, in multivariate analysis, with a level of pregraft M‐MDSC above 1.4% (HR: 55.01 [14.95–202.37], p

Published
2023
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4. Successful treatment of congenital erythropoietic porphyria using matched unrelated hematopoietic stem cell transplantation in an adult: A case report

Author

Pierre Peterlin, Julia Bonnelye, Alice Garnier, Amandine Le Bourgeois, Thierry Guillaume, Maxime Jullien, Hervé Dutartre, Marie Le Moigne, Caroline Schmitt, Laurent Gouya, Antoine Poli, Sebastien Barbarot, and Patrice Chevallier

Subjects
Dermatology, RL1-803
Abstract

Abstract Congenital erythropoietic porphyria (CEP), or Gunther disease, is a rare genetic disease responsible for severe dermatologic, hepatic and/or haematological damages related to the deficient activity of the uroporphyrinogen III synthase. Allogeneic stem cell transplantation (Allo‐SCT) represents the only curative treatment and few allotransplanted cases have been reported in children but not in adults. Here we report for the first time the successful cure of a 46‐year old man with CEP with a 5‐year follow‐up after Allo‐SCT.

Published
2024
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5. Tocilizumab in combination with a standard induction chemotherapy in acute myeloid leukaemia patients (TOCILAM study): a single-centre, single-arm, phase 1 trialResearch in context

Author

Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Thierry Guillaume, Yannick Le Bris, Olivier Theisen, Marie C. Béné, Marion Eveillard, Marie Rimbert, Maxime Jullien, Lucie Planche, Joelle Gaschet, and Patrice Chevallier

Subjects
Acute myeloid leukaemia, Induction chemotherapy, IL-6, Tocilizumab, Medicine (General), R5-920
Abstract

Summary: Background: In acute myeloid leukaemia (AML), interleukin-6 (IL-6) promotes chemo-resistance and its levels correlate with poor prognosis. IL-6 blockade may represent a promising therapeutic strategy. We aimed to test, tocilizumab, an anti-IL-6 receptor (R) monoclonal antibody in combination with standard intensive AML induction chemotherapy. Methods: This investigator-initiated single-centre phase 1 trial was conducted at Nantes University Hospital in France. According to a continual reassessment method, three escalating doses were tested of intravenous (IV) tocilizumab (4, 6, and 8 mg/kg) administered at day (d) 8 of a standard AML induction chemotherapy (IV idarubicine 8 mg/m2 d1 to d5 + IV cytarabine 100 mg/m2 d1 to d7). All adults (aged ≥ 18 years) with an Eastern Cooperative Oncology Group performance status of 0–2 and with a newly diagnosed (excluding patients with a favourable risk according to ELN-2017 classification if

Published
2023
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7. 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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8. Efficacy of anti‐severe acute respiratory syndrome coronavirus 2 mRNA vaccines in adults with severe acquired aplastic anemia with or without allogeneic hematopoietic stem cell transplantation

Author

Alice Garnier, Amandine Le Bourgeois, Thierry Guillaume, Pierre Peterlin, Maxime Jullien, Marianne Coste‐Burel, Marie C Béné, and Patrice Chevallier

Subjects
allogeneic, aplastic anemia, BNT162b2, COVID‐19, SARS‐CoV‐2 mRNA, third dose, Diseases of the blood and blood-forming organs, RC633-647.5
Published
2022
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9. Anti‐SARS‐CoV‐2 vaccines in recipient and/or donor before allotransplant

Author

Maxime Jullien, Marianne Coste‐Burel, Beatrice Clemenceau, Valentin Letailleur, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Berthe‐Marie Imbert, Jocelyn Ollier, Audrey Grain, Cyrille Touzeau, Philippe Moreau, Marie C Béné, Henri Vié, and Patrice Chevallier

Subjects
allogeneic, cellular response, COVID‐19, hematological, humoral response, SARS‐CoV‐2 mRNA, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract The impact of pre‐transplant anti‐severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) vaccine in 20 recipients of allogeneic hematopoietic stem cell transplantation (Allo‐HSCT) and/or their donors is reported here, showing that the persistence of anti‐SARS‐CoV‐2 antibodies can be detected in almost all patients, whatever the type of vaccine used, and up to 9 months post transplant. Also, an anti‐SARS‐CoV‐2 spike glycoprotein CD3+ T‐cell response could be detected in six (35%) of 17 evaluable patients. This study provides a rationale to consider anti‐SARS‐CoV‐2 vaccination of both recipients and donors before Allo‐HSCT.

Published
2022
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10. Post‐transplant cyclophosphamide as sole GHVD prophylaxis after matched reduced‐intensity conditioning allotransplant

Author

Amandine Le Bourgeois, Maxime Jullien, Alice Garnier, Pierre Peterlin, Marie C. Béné, Thierry Guillaume, and Patrice Chevallier

Subjects
allogeneic, ATG, clofarabine, GVHD prophylaxis, matched, PTCY, Medicine (General), R5-920
Abstract

Abstract Background Post‐transplant cyclophosphamide (PTCY) alone as graft‐versus‐host disease (GVHD) prophylaxis may avoid/reduce short‐ and mid‐term toxicities of drugs commonly used for GVHD prophylaxis, accelerate immune reconstitution after the graft to decrease infections and facilitate the early integration of adjunct maintenance therapies to prevent relapse. Objective A prospective phase 2 study was designed in order to assess the feasibility and safety of PTCY as a sole GVHD prophylaxis in adult patients receiving a Baltimore‐based reduced‐intensity conditioning (RIC) peripheral blood (PB) allogeneic hematopoietic stem cell transplantation (Allo‐HSCT) with a matched donor. Study design Patients were planned to be included stepwise up to 59 evaluable PTCY recipients, in order to be able to stop the protocol in case of excessive corticosteroid resistant grade 3–4 severe acute GVHD (aGVHD). Because a high incidence of grade 2–4 aGVHD was observed after analysis of the first 27 patients, the protocol was amended to test the addition of 1 day of anti‐thymoglobulin to PTCY. In spite of this, the trial had to be stopped after 38 treated patients, because of an unacceptable rate of grade 3–4 aGVHD. Donors were matched related to 12 patients and unrelated to 26. Results With a median follow‐up of 29.6 months, 2‐year overall, disease‐free and GVHD‐free relapse‐free (GRFS) survivals were respectively 65.4%, 62.1% and 46.9%. Cumulative incidences of grade 2–4 and 3–4 aGVHD at day 100 were 52.6% and 21.1%, respectively, while that of moderate/severe chronic(c) GVHD was 15.7% at 2 years. Addition of ATG to PTCY did influence neither aGVHD, cGVHD nor GRFS. Conclusion Despite paradoxically good survivals, especially GRFS, this study failed to demonstrate that PTCY (± ATG) alone can be used for Baltimore‐based RIC PB Allo‐HSCT with matched donors. Other combinations should be tested to try and avoid long‐term use of immunosuppressive drugs following Allo‐HSCT in this setting.

Published
2023
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11. Impact of allogeneic stem cell transplantation comorbidity indexes after haplotransplant using post‐transplant cyclophosphamide

Author

Maxime Jullien, Corentin Orvain, Ana Berceanu, Marie‐Anne Couturier, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Marion Klemencie, Aline Schmidt, Mathilde Hunault, Etienne Daguindau, Xavier Roussel, Pascal Delepine, Gaelle Guillerm, Aurelien Giltat, Sylvie François, Sylvain Thepot, Steven Le Gouill, Marie‐C Béné, and Patrice Chevallier

Subjects
allogeneic hematopoietic stem cell transplantation, augmented comorbidity/age index, comorbidity/age index, haploidentical, HSCT‐CI, PTCY, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Three different scoring systems have been developed to assess pre‐transplant comorbidity in allogeneic hematopoietic stem cell transplantation (Allo‐HSCT): the Hematopoietic Cell Transplantation‐Specific Comorbidity Index, the Comorbidity/Age index, and the Augmented Comorbidity/Age index. All were devised to predict overall survival (OS) and disease‐free survival (DFS) survivals and non‐relapse mortality (NRM) in patients receiving HLA‐matched Allo‐HSCT, but their performance has scarcely been studied in the haploidentical Allo‐HSCT setting with post‐transplant cyclophosphamide, a procedure in constant expansion worldwide. Methods To address this issue, their impact on survivals and NRM was examined in a cohort of 223 patients treated with haploidentical Allo‐HSCT in four different centers. Results With a median follow‐up of 35.6 months, 3‐year OS, DFS, and NRM were 48.1% ± 4%, 46.3% ± 4%, and 30.0% ± 3%, respectively. No impact was found for any of the three comorbidity scores in univariate analysis. In multivariate analyses, the only three factors associated with lower OS were DRI (p

Published
2021
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12. Safety and immunogenicity of a first dose of SARS‐CoV‐2 mRNA vaccine in allogeneic hematopoietic stem‐cells recipients

Author

Patrice Chevallier, Marianne Coste‐Burel, Amandine Le Bourgeois, Pierre Peterlin, Alice Garnier, Marie C. Béné, Berthe‐Marie Imbert, Thomas Drumel, Steven Le Gouill, Philippe Moreau, Beatrice Mahe, Viviane Dubruille, Nicolas Blin, Anne Lok, Cyrille Touzeau, Thomas Gastinne, Maxime Jullien, Sophie Vanthygem, and Thierry Guillaume

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

Abstract This was a monocentric prospective study testing the efficacy and safety of a first injection of BNT162b2 (Pfizer‐BioNTech) in 112 Allo‐HSCT patients. Antibody response to SARS‐CoV‐2 spike protein receptor‐binding domain was tested at the time of the second injection (Roche Elecsys). The study also included a non‐randomized control arm of 26 healthy controls. This study shows that a first dose of SARS‐CoV‐2 messenger RNA vaccine is safe and provides a 55% rate of seroconversion in allotransplanted patients compared to 100% for the controls (p

Published
2021
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13. A new cytokine‐based dynamic stratification during induction is highly predictive of survivals in acute myeloid leukemia

Author

Pierre Peterlin, Joelle Gaschet, Thierry Guillaume, Alice Garnier, Marion Eveillard, Amandine Le Bourgeois, Michel Cherel, Camille Debord, Yannick Le Bris, Olivier Theisen, Catherine Godon, Béatrice Mahé, Viviane Dubruille, Soraya Wuilleme, Cyrille Touzeau, Thomas Gastinne, Nicolas Blin, Anne Lok, Benoît Tessoulin, Steven Le Gouill, Philippe Moreau, Marie‐C Béné, and Patrice Chevallier

Subjects
acute myeloid leukemia, FLT3 ligand, IL‐6, prognostic biomarker, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract The aim of this study was to assess the potential impact of the kinetics of serum levels of seven cytokines during induction in acute myeloid leukemia (AML) patients. Indeed, the role of cytokines, in the pathophysiology and response to therapy of AML patients, remains under investigation. Here, we report on the impact of peripheral levels of two cytokines, the Fms‐like tyrosine kinase 3 ligand (FL) and interleukin‐6 (IL‐6), evaluated during first‐line intensive induction. A new risk stratification can be proposed, which supersedes the ELN 2017 classification to predict survivals in AML patients by examining the kinetic profile of these cytokines during the induction phase. It segregates three groups of, respectively, high‐risk, characterized by a stagnation of low FL levels, intermediate risk, with dynamic increasing FL levels and high IL‐6 at day 22, and favorable risk with increasing FL levels but low IL‐6 at day 22.

Published
2021
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14. Strong SARS-CoV-2 T-Cell Responses after One or Two COVID-19 Vaccine Boosters in Allogeneic Hematopoietic Stem Cell Recipients

Author

Béatrice Clémenceau, Amandine Le Bourgeois, Thierry Guillaume, Marianne Coste-Burel, Pierre Peterlin, Alice Garnier, Maxime Jullien, Jocelyn Ollier, Audrey Grain, Marie C. Béné, and Patrice Chevallier

Subjects
allogeneic hematopoietic stem cell transplantation, COVID-19, anti-SARS-CoV-2 vaccines, booster, humoral immunity, cellular immunity, Cytology, QH573-671
Abstract

A full exploration of immune responses is deserved after anti-SARS-CoV-2 vaccination and boosters, especially in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although several reports indicate successful humoral responses in such patients, the literature is scarce on cellular specific immunity. Here, both B- (antibodies) and T-cell responses were explored after one (V3 n = 40) or two (V4 n = 12) BNT162b2 mRNA vaccine boosters in 52 allo-HSCT recipients at a median of 755 days post-transplant (n = 9). Results were compared with those of 12 controls who had received only one booster (BNT162b2 n = 6; mRNA-1273 n = 6). All controls developed protective antibody levels (>250 BAU/mL) and anti-spike T-cell responses. Similarly, 81% of the patients developed protective antibody levels, without difference between V3 and V4 (82.5% vs. 75%, p = 0.63), and 85% displayed T-cell responses. The median frequency of anti-spike T cells did not differ either between controls or the whole cohort of patients, although it was significantly lower for V3 (but not V4) patients. COVID-19 infections were solely observed in individuals having received only one booster. These results indicate that four vaccine injections help to achieve a satisfactory level of both humoral and cellular immune protection in allo-HSCT patients.

Published
2022
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15. SARS-CoV-2 T-Cell Responses in Allogeneic Hematopoietic Stem Cell Recipients following Two Doses of BNT162b2 mRNA Vaccine

Author

Béatrice Clémenceau, Thierry Guillaume, Marianne Coste-Burel, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Maxime Jullien, Jocelyn Ollier, Audrey Grain, Marie C. Béné, Henri Vié, and Patrice Chevallier

Subjects
COVID 19, vaccine, BNT162b2, SARS-CoV-2 mRNA, allogeneic hematopoietic stem cell transplantation, cellular immunity, Medicine
Abstract

Background: At variance to humoral responses, cellular immunity after anti-SARS-CoV-2 vaccines has been poorly explored in recipients of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT), especially within the first post-transplant years where immunosuppression is more profound and harmful. Methods: SARS-CoV-2 Spike protein-specific T-cell responses were explored after two doses of BNT162b2 mRNA vaccine in 45 Allo-HSCT recipients with a median time from transplant of less than 2 years by using INF-γ ELISPOT assay and flow-cytometry enumeration of CD4+ and CD8+ T lymphocytes with intracellular cytokine production of IFN-γ and TNF-α. Results: A strong TNF-α+ response from SARS-CoV-2-specific CD4+ T-cells was detected in a majority of humoral responders (89%) as well as in a consistent population of non-humoral responders (40%). Conclusions: T-cells are likely to participate in protection against COVID-19 viral infection, even in the absence of detectable antibody response, especially in the first years post-transplant in Allo-HSCT recipients.

Published
2022
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16. Diagnosis and prognosis are supported by integrated assessment of next-generation sequencing in chronic myeloid malignancies. A real-life study

Author

Sophie Vantyghem, Pierre Peterlin, Sylvain Thépot, Audrey Ménard, Viviane Dubruille, Camille Debord, Thierry Guillaume, Alice Garnier, Amandine Le Bourgeois, Soraya Wuilleme, Catherine Godon, Olivier Theisen, Marion Eveillard, Jacques Delaunay, Hervé Maisonneuve, Nadine Morineau, Bruno Villemagne, Stéphane Vigouroux, François Subiger, Elsa Lestang, Marion Loirat, Anne Parcelier, Pascal Godmer, Mélanie Mercier, Adrien Trebouet, Damien Luque Paz, Ronan Le Calloch, Lenaig Le Clech, Céline Bossard, Anne Moreau, Valérie Ugo, Mathilde Hunault, Philippe Moreau, Steven Le Gouill, Patrice Chevallier, Marie C. Béné, and Yannick Le Bris

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

Next-generation sequencing (NGS) is used to investigate the presence of somatic mutations. The utility of incorporating routine sequencing to guide diagnosis and therapeutic decisions remains unclear. We report the findings of an observational, multicenter study that aimed to assess the impact of somatic mutation testing by NGS in a reallife setting of chronic myeloid malignancies. A total of 177 patients were enrolled, partitioned into two overlapping groups. In group A (n=94), the indication was to search for clonal hematopoiesis, in a context of suspected myelodysplastic syndrome or myeloproliferative neoplasia. In group B (n=95), the theranostic impact of somatic mutations was studied. A panel of 34 genes was used on DNA extracted from blood or bone marrow samples. Within group A, the detection of clonal hematopoiesis supported the diagnosis of chronic myeloid malignancies for 31 patients while the absence of clonal hematopoiesis ruled out the suspected diagnosis in 47 patients. Within group B, NGS identified prognostically relevant somatic mutations in 32 patients, which had a therapeutic impact in 18 cases. By determining the presence or absence of somatic mutations, the application of NGS in daily practice was found to be useful for an integrated final diagnosis in 83% of the patients. Moreover, the search for somatic mutations had a prognostic impact that led to treatment modification in 19% of the cases. This study outlines the fact that adequate implementation of new investigations may have a significant positive medico-economic impact by enabling appropriate management of patients.

Published
2020
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17. FLT3 ligand plasma levels in acute myeloid leukemia

Author

Pierre Peterlin, Joelle Gaschet, Thierry Guillaume, Alice Garnier, Marion Eveillard, Amandine Le Bourgeois, Michel Cherel, Camille Debord, Yannick Le Bris, Olivier Theisen, Béatrice Mahé, Viviane Dubruille, Catherine Godon, Nelly Robillard, Soraya Wuilleme, Cyrille Touzeau, Thomas Gastinne, Nicolas Blin, Anne Lok, Antoine Bonnet, Steven Le Gouill, Philippe Moreau, Marie-C Béné, and Patrice Chevallier

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2019
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18. Low to undetectable Omicron BQ.1.1 neutralization by patient’s sera a month after initiation of AZD7442 600 mg

Author

Franck Touret, Guillaume Martin-Blondel, Xavier de Lamballerie, Axelle Dupont, Jacques Izopet, France Mentré, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Christophe Richez, Lionel Couzi, Aliénor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Dany Anglicheau, Morgane Cheminant, Yazdan Yazdanpanah, Stéphanie N’Guyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Sabrina Kali, Denis Angoulvant, Karine Barthélémy, Stéphane Priet, Elif Nurtop, Ventzislava Petrov Sanchez, Coralie Tardivon, Gilles Blancho, Amandine Le Bourgeois, and Vincent Lévy

Subjects
Microbiology (medical), Infectious Diseases
Published
2023

19. Low serum neutralization of Omicron variants a month after AZD7442 prophylaxis initiation

Author

Xavier de Lamballerie, Guillaume Martin-Blondel, Axelle Dupont, Jacques Izopet, France Mentré, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Amandine le Bourgeois, Christophe Richez, Lionel Couzi, Aliénor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Denis Anglicheau, Morgane Cheminant, Yazdan Yazdanpanah, Stéphanie N Guyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Sabrina Kali, Denis Angoulvant, Ventzislava Petrov Sanchez, Coralie Tardivon, Gilles Blancho, Vincent Lévy, 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 Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), 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), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), CHU Strasbourg, Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hematologie [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest (RESO), CHU Bordeaux [Bordeaux], Hopital Saint-Louis [AP-HP] (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Hôpital Cochin [AP-HP], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
Microbiology (medical), Infectious Diseases, [SDV]Life Sciences [q-bio]
Published
2023

20. Peripheral levels of monocytic myeloid‐derived suppressive cells before and after first induction predict relapse and survivals in <scp>AML</scp> patients

Author

Pierre Peterlin, Camille Debord, Marion Eveillard, Alice Garnier, Amandine Le Bourgeois, Thierry Guillaume, Maxime Jullien, Marie C. Béné, and Patrice Chevallier

Subjects
Adult, Leukemia, Myeloid, Acute, Humans, Molecular Medicine, Myeloid Cells, Prospective Studies, Cell Biology, Neoplasm Recurrence, Local, Monocytes
Abstract

Myeloid Derived Suppressive Cells (MDSC) are capable to suppress innate and adaptive immune responses, thus favouring solid cancer progression. However, little is known about the role of MDSC in acute myeloid leukaemia (AML). In this monocentric prospective study, 73 adult AML patients, eligible for first-line intensive chemotherapy, were included with the aim to study the influence on long-term outcomes of peripheral blood (PB) levels of monocytic (M) MDSC (M-MDSC) assessed by flow cytometry. A percentage of peripheral M-MDSC higher than 0.55% of leukocytes at diagnosis and a decrease of M-MDSC% after induction came out both as independent negative prognostic factors for leukaemia-free and overall survival.

Published
2022

21. Safety and risk of febrile recurrence after early antibiotic discontinuation in high-risk neutropenic patients with haematological malignancies: a multicentre observational study

Author

Raphael Paret, Amandine Le Bourgeois, Gaëlle Guillerm, Benoit Tessoulin, Schéhérazade Rezig, Thomas Gastinne, Marie Anne Couturier, David Boutoille, Raphael Lecomte, Florence Ader, Steven Le Gouill, Séverine Ansart, Jean Philippe Talarmin, and Benjamin Gaborit

Subjects
Pharmacology, Microbiology (medical), Leukemia, Myeloid, Acute, Neutropenia, Infectious Diseases, Hematologic Neoplasms, Neoplasms, Humans, Bacteremia, Pharmacology (medical), Prospective Studies, Fever of Unknown Origin, Anti-Bacterial Agents
Abstract

Background Early antibiotic discontinuation according to the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations is not systematically applied in high-risk neutropenic patients with haematological malignancies. Methods A retrospective multicentre observational study was conducted over 2 years to evaluate the safety of early antibiotic discontinuation for fever of unknown origin (FUO) during neutropenia after induction chemotherapy or HSCT, in comparison with a historical cohort. We used Cox proportional hazards models, censored on neutropenia resolution, to analyse factors associated with febrile recurrence. Results Among 147 included patients in the ECIL-4 cohort, mainly diagnosed with acute leukaemia (n = 104, 71%), antibiotics were discontinued during 170 post-chemotherapy neutropenic episodes. In comparison with the historical cohort of 178 episodes of neutropenia without antibiotic discontinuation, no significant differences were observed regarding febrile recurrences [71.2% (121/170) versus 71.3% (127/178), P = 0.97], admission in ICUs [6.5% (11/170) versus 11.2% (20/178), P = 0.17], septic shock [0.6% (1/170) versus 3.9% (7/178), P = 0.07] and 30 day mortality [1.4% (2/147) versus 2.7% (4/150), P = 0.084]. In the ECIL-4 cohort, the rate of bacteraemia in case of febrile recurrence was higher [27.1% (46/170) versus 11.8% (21/178), P Conclusions After an FUO episode in high-risk neutropenia, compliance with ECIL-4 recommendations for early antibiotic discontinuation appears to be safe and mucosal damage was associated with febrile recurrence and bacteraemia. Prospective interventional studies are warranted to assess this strategy in high-risk neutropenic patients.

Published
2022

23. 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

24. Dramatic Recovery after Etoposide Phosphate Infusion for Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome following Treatment with Tisagenlecleucel in a Young Patient with Relapsed Acute Lymphoblastic Leukemia: A Case Report

Author

Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Maxime Jullien, Amélie Seguin, Marion Eveillard, Marie-Christine Béné, Thierry Guillaume, and Patrice Chevallier

Subjects
Hematology, General Medicine
Abstract

The occurrence of a secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) after CAR T-cell infusion is very rare and mostly fatal. Treatment recommendations for such a complication are not yet established. Here, we report the dramatic recovery of HLH/MAS following tisagenlecleucel infusion in a young patient with relapsed acute lymphoblastic leukemia using etoposide phosphate (EP). We propose that monitoring for the occurrence of HLH/MAS should be part of surveillance after CAR T-cell infusion and that EP treatment appears to be useful to control this severe and rare complication.

Published
2022

25. Assessment of COVID-19 Incidence and Severity Among Recipients of Allogenic Stem Cell Transplant After 1 or 2 mRNA Booster Doses During the Omicron Wave in France

Author

Valentin Letailleur, Amandine Le Bourgeois, Thierry Guillaume, Maxime Jullien, Marianne Coste-Burel, Marie C. Béné, and Patrice Chevallier

Subjects
General Medicine
Abstract

This cohort study assesses the incidence and severity of COVID-19 among vaccinated recipients of allogenic stem cell transplant in a single center after 1 or 2 messenger RNA booster doses during the Omicron wave in France.

Published
2022

26. 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

27. Effectiveness of a third dose of BNT162b2 anti‐SARS‐CoV‐2 mRNA vaccine over a 6‐month follow‐up period in allogenic hematopoietic stem cells recipients

Author

Patrice Chevallier, Maxime Jullien, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Marianne Coste‐Burel, Marie C. Béné, and Thierry Guillaume

Subjects
Cancer Research, Oncology, Hematology, General Medicine
Abstract

This study reports the effectiveness of three injections of BNT162b2 anti-SARS-CoV-2 mRNA vaccine in 141 Allo-HSCT recipients with a median follow-up of 6 months post-third shot. We demonstrate a long-term high protection of Allo-HSCT recipients since only 2 infections and one death related to COVID-19 occurred.

Published
2022

29. CD73-Expressing Microbiota-Reactive DP8α Regulatory T Cells Are Lacking in Acute GvHD Patients and Prevent Disease Development in a Pre-Clinical In Vivo Humanized Mouse Model of GvHD

Author

Emmanuelle Godefroy, Patrice Chevallier, Fabienne Haspot, Caroline Vignes, Véronique Daguin, Sylvia Lambot, Thierry Guillaume, Margaux Verdon, Pierre Peterlin, Alice Garnier, Maxence Mougon, Amandine Le Bourgeois, Maxime Jullien, Francine Jotereau, and Frédéric Altare

Subjects
Immunology, Cell Biology, Hematology, Biochemistry
Published
2022

35. A new cytokine‐based dynamic stratification during induction is highly predictive of survivals in acute myeloid leukemia

Author

Amandine Le Bourgeois, Marion Eveillard, Camille Debord, Joëlle Gaschet, Marie-C. Béné, Cyrille Touzeau, Soraya Wuilleme, Michel Chérel, Thierry Guillaume, Thomas Gastinne, Patrice Chevallier, Philippe Moreau, Catherine Godon, Benoit Tessoulin, Beatrice Mahe, Olivier Theisen, Nicolas Blin, Alice Garnier, Viviane Dubruille, Anne Lok, Pierre Peterlin, Yannick Le Bris, Steven Le Gouill, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), CRLCC René Gauducheau, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), 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), and Bernardo, Elizabeth

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Response to therapy, medicine.medical_treatment, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, prognostic biomarker, Original Research, Potential impact, biology, Myeloid leukemia, Induction Chemotherapy, Middle Aged, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Pathophysiology, 3. Good health, Survival Rate, Leukemia, Myeloid, Acute, Cytokine, 030220 oncology & carcinogenesis, Female, Adult, medicine.medical_specialty, Induction Phase, [SDV.CAN]Life Sciences [q-bio]/Cancer, acute myeloid leukemia, lcsh:RC254-282, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Biomarkers, Tumor, Humans, FLT3 ligand, Radiology, Nuclear Medicine and imaging, Interleukin 6, Aged, IL-6, business.industry, Interleukin-6, Clinical Cancer Research, Membrane Proteins, IL‐6, 030104 developmental biology, biology.protein, business, Intermediate risk, Follow-Up Studies
Abstract

The aim of this study was to assess the potential impact of the kinetics of serum levels of seven cytokines during induction in acute myeloid leukemia (AML) patients. Indeed, the role of cytokines, in the pathophysiology and response to therapy of AML patients, remains under investigation. Here, we report on the impact of peripheral levels of two cytokines, the Fms‐like tyrosine kinase 3 ligand (FL) and interleukin‐6 (IL‐6), evaluated during first‐line intensive induction. A new risk stratification can be proposed, which supersedes the ELN 2017 classification to predict survivals in AML patients by examining the kinetic profile of these cytokines during the induction phase. It segregates three groups of, respectively, high‐risk, characterized by a stagnation of low FL levels, intermediate risk, with dynamic increasing FL levels and high IL‐6 at day 22, and favorable risk with increasing FL levels but low IL‐6 at day 22., Here we report on the impact of the peripheral levels of two cytokines, the Fms‐like tyrosine kinase 3 ligand (FL), and interleukin‐6 (IL‐6), evaluated during first‐line intensive induction. Indeed, a new risk stratification can be proposed, which supersedes the ELN 2017 classification to predict survivals in AML patients by examining their profile during the induction phase.

Published
2021

36. Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study

Author

Marie-Therese Rubio, Roberta Di Blasi, Gilles Salles, Miguel A Perales, Kada Klouche, Muriel Picard, Pierre Sesques, Eric Mariotte, Michael Darmon, Boris Böll, Philippe R. Bauer, Sanjay Chawla, Kevin Rakszawski, Nahema Issa, Anne Huynh, Guillaume Cartron, Florence Rabian, Peter Borchmann, Michael Joannidis, Sabine Furst, Sophie de Guibert, Lara Zafrani, Patrice Ceballos, Nicolas Boissel, David Beauvais, Catherine Thieblemont, François-Xavier Gros, Alberto Mussetti, Gabriel Moreno-González, Adel Maamar, Florent Wallet, Faezeh Legrand, Julien Leroy, Quentin Quelven, Djamel Mokart, Valentin Ortiz, Christian Recher, Jakob Rudzki, Laura Platon, Pleun Hemelaar, Benoit Tessoulin, Reuben Benjamin, Sandrine Valade, Pedro Castro, Gennadii Galstian, Amélie Seguin, Peter Schellongowski, Anna Sureda, Alice Gallo De Moraes, Philipp Wohlfarth, Bruno Levy, Andry Van de Louw, Jorge Garcia Borrega, Julio Delgado, Ibrahim Yakoub-Agha, Nathalie Fégueux, Laveena Munshi, Yi Lin, Emmanuel Bachy, Stéphanie Harel, Sara Fernández, Bertrand Arnulf, Thomas Gastinne, Elie Azoulay, Didier Blaise, Amandine Le Bourgeois, Louis Voigt, Cécile Borel, Anne-Sophie Moreau, Christian Chabannon, Ulrich Jäger, Virginie Lemiale, Olga Gavrilina, Victoria Metaxa, Thomas Staudingert, Edouard Forcade, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Barcelona, 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), King's College Hospital (KCH), Mayo Clinic [Rochester], Memorial Sloane Kettering Cancer Center [New York], Weill Medical College of Cornell University [New York], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Hôpital Roger Salengro [Lille], Penn State Health Milton S. Hershey Medical Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Universitätsklinikum Köln (Uniklinik Köln), Hôpital Saint-André, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Radboud University Medical Center [Nijmegen], Universitat de Barcelona (UB), University of Toronto, Medizinische Universität Wien = Medical University of Vienna, Leopold Franzens Universität Innsbruck - University of Innsbruck, 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), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Soins Intensifs [CHRU Nancy], Radboud University Medical Centre [Nijmegen, The Netherlands], University of Innsbruck, and National Research Center for Hematology [Moscow, Russia]

Subjects
Male, MESH: Neurotoxicity Syndromes, MESH: Registries, [SDV]Life Sciences [q-bio], MESH: Multiple Myeloma, Immunotherapy, Adoptive, Severity of Illness Index, law.invention, MESH: Proportional Hazards Models, Medicina intensiva, Clinical trials, 0302 clinical medicine, law, Clinical endpoint, Medicine, Infection control, Registries, MESH: Treatment Outcome, MESH: Middle Aged, Medical record, Hazard ratio, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, MESH: Follow-Up Studies, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Intensive care unit, 3. Good health, Survival Rate, Cytokine release syndrome, Intensive Care Units, Treatment Outcome, 030220 oncology & carcinogenesis, MESH: Immunotherapy, Adoptive, Female, Neurotoxicity Syndromes, Lymphoma, Large B-Cell, Diffuse, Cytokine Release Syndrome, Multiple Myeloma, Care of the sick, Cohort study, Adult, medicine.medical_specialty, Critical Care, MESH: Survival Rate, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], MESH: Cytokine Realease Syndrome, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, MESH: Critical Care, Internal medicine, Intensive care, MESH: Severity of Illness Index, Humans, Cura dels malalts, Critical care medicine, Proportional Hazards Models, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, business.industry, MESH: Lymphomz, Large B-Cell, Diffuse, MESH: Adult, MESH: Intensive care Units, medicine.disease, MESH: Male, business, MESH: Female, Assaigs clínics, 030215 immunology, Follow-Up Studies
Abstract

Summary Background Chimeric antigen receptor (CAR) T-cell therapy can induce side-effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), which often require intensive care unit admission. The aim of this study was to describe management of critically ill CAR T-cell recipients in intensive care. Methods This international, multicentre, observational cohort study was done in 21 intensive care units in France, Spain, the USA, the UK, Russia, Canada, Germany, and Austria. Eligible patients were aged 18 years or older; had received CAR T-cell therapy in the past 30 days; and had been admitted to intensive care for any reason. Investigators retrospectively included patients admitted between Feb 1, 2018, and Feb 1, 2019, and prospectively included patients admitted between March 1, 2019, and Feb 1, 2020. Demographic, clinical, laboratory, treatment, and outcome data were extracted from medical records. The primary endpoint was 90-day mortality. Factors associated with mortality were identified using a Cox proportional hazard model. Findings 942 patients received CAR T-cell therapy, of whom 258 (27%) required admission to intensive care and 241 (26%) were included in the analysis. Admission to intensive care was needed within median 4·5 days (IQR 2·0–7·0) of CAR T-cell infusion. 90-day mortality was 22·4% (95% CI 17·1–27·7; 54 deaths). At initial evaluation on admission, isolated cytokine release syndrome was identified in 101 patients (42%), cytokine release syndrome and ICANS in 93 (39%), and isolated ICANS in seven (3%) patients. Grade 3–4 cytokine release syndrome within 1 day of admission to intensive care was found in 50 (25%) of 200 patients and grade 3–4 ICANS in 38 (35%) of 108 patients. Bacterial infection developed in 30 (12%) patients. Life-saving treatments were used in 75 (31%) patients within 24 h of admission to intensive care, primarily vasoactive drugs in 65 (27%) patients. Factors independently associated with 90-day mortality by multivariable analysis were frailty (hazard ratio 2·51 [95% CI 1·37–4·57]), bacterial infection (2·12 [1·11–4·08]), and lifesaving therapy within 24 h of admission (1·80 [1·05–3·10]). Interpretation Critical care management is an integral part of CAR T-cell therapy and should be standardised. Studies to improve infection prevention and treatment in these high-risk patients are warranted. Funding Groupe de Recherche Respiratoire en Reanimation Onco-Hematologique.

Published
2021

37. Grade 2 acute GVHD is a factor of good prognosis in patients receiving peripheral blood stem cells haplo-transplant with post-transplant cyclophosphamide

Author

Steven Le Gouill, Ana Berceanu, A. Dormoy, Patrice Chevallier, Yohan Desbrosses, Caroline Malugani, Céline Bressollette, Berthe-Marie Imbert, Benoit Tessoulin, Thomas Gastinne, Eric Deconinck, Beatrice Mahe, Nicolas Blin, Philippe Moreau, Thierry Guillaume, Marie C. Béné, Marion Eveillard, Sophie Vantyghem, Amandine Le Bourgeois, Alix Duquesne, Etienne Daguindau, Yannick Le Bris, Alice Garnier, Cyrille Touzeau, Viviane Dubruille, Anne Lok, and Pierre Peterlin

Subjects
Adult, Male, medicine.medical_specialty, Transplantation Conditioning, Post transplant cyclophosphamide, Graft vs Host Disease, Peripheral Blood Stem Cells, Gastroenterology, 030218 nuclear medicine & medical imaging, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Immune system, immune system diseases, Internal medicine, Acute graft versus host disease, medicine, Humans, Clofarabine, Radiology, Nuclear Medicine and imaging, In patient, Cyclophosphamide, Aged, Retrospective Studies, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, General Medicine, Middle Aged, Prognosis, Peripheral blood, surgical procedures, operative, Oncology, 030220 oncology & carcinogenesis, Female, Good prognosis, business, medicine.drug
Abstract

The impact of acute graft versus host disease (GVHD) on survivals for patients receiving a haploidentical allogeneic stem-cell transplant (Allo-SCT) with peripheral blood stem-cells (PBSC) complemented by post-transplant cyclophosphamide (PTCY) is ill-known.This retrospective study included 131 patients who received a PBSC haplograft in order to precise the impact of acute GVHD on outcomes. There were 78 males and 53 females and the median age for the whole cohort was 59 years (range: 20-71). Thirty-five patients were allografted for a lymphoid disease and 96 for a myeloid malignancy, including 67 patients with acute myeloid leukemia (AML).The cumulative incidence (CI) of day 100 grade 2-4 and 3-4 acute GVHD was 43.4 + 4.6% and 16.7 + 3.4%, respectively. The 2-year CI of moderate/severe chronic GVHD was 10.1 + 2.8%. The only factor affecting the occurrence of GVHD was GVHD prophylaxis. Indeed, CI of day 100 grade 2-4 (but not grade 3-4) acute GVHD was significantly reduced when adding anti-thymoglobulin (ATG) to PTCY. However, in multivariate analysis, grade 2 acute GVHD was significantly associated with better disease-free (HR: 0.36; 95%CI: 0.19-0.69,Acute grade 2 GVHD is a factor of good prognosis after PBSC haplotransplant with PTCY. Further and larger studies are needed to clarify the complex question of GVHD prophylaxis in the setting of haplo-transplant, especially that of combining ATG and PTCY.

Published
2020

38. Sequential allogeneic hematopoietic stem cell transplantation for active refractory/relapsed myeloid malignancies: results of a reduced-intensity conditioning preceded by clofarabine and cytosine arabinoside, a retrospective study on behalf of the SFGM-TC

Author

Natacha Maillard, Sylvain Chantepie, Tony Marchand, Myriam Labopin, Régis Peffault de Latour, Ibrahim Yakoub-Agha, Karin Bilger, Didier Blaise, Pascal Turlure, Marie C. Béné, Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Mohamad Mohty, Marie-Thérèse Rubio, Patrice Chevallier, Stéphanie Nguyen, Edouard Forcade, Patrice Ceballos, Anne Huynh, Amandine Charbonnier, Ambroise Marçais, Amandine Le Bourgeois, Thierry Guillaume, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pathologies biliaires, fibrose et cancer du foie [CRSA], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pitié-Salpêtrière [AP-HP], Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Bordeaux [Bordeaux], 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), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), CHU Amiens-Picardie, CHU Limoges, 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), 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), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], 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)-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), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Toulouse [Toulouse], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and 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)

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Transplantation Conditioning, Adolescent, Cyclophosphamide, medicine.medical_treatment, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Clofarabine, education, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Chemotherapy, education.field_of_study, business.industry, Cytarabine, Hematopoietic Stem Cell Transplantation, Hematology, General Medicine, Middle Aged, Allografts, 3. Good health, Survival Rate, Transplantation, Leukemia, Myeloid, Acute, Regimen, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Busulfan, 030215 immunology, medicine.drug
Abstract

Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern.

Published
2020

39. Azacitidine in patients older than 80 years with acute myeloid leukaemia or myelodysplastic syndromes: a report on 115 patients

Author

Steven Le Gouill, Anne‐Marie Ngo Nloga, Cecile Bally, Thierry Guillaume, Thomas Cluzeau, Anne Calleja, Patrice Chevallier, Pierre Fenaux, Eurydice Angeli, Maxime Jullien, Alice Garnier, Pierre Peterlin, Lionel Ades, and Amandine Le Bourgeois

Subjects
Oncology, medicine.medical_specialty, business.industry, Myelodysplastic syndromes, Azacitidine, MEDLINE, Hematology, medicine.disease, Internal medicine, medicine, In patient, Myeloid leukaemia, business, medicine.drug
Published
2020

40. Absence of influence of peripheral blood CD34+ and CD3+ graft cell counts on outcomes after reduced-intensity conditioning transplantation using post-transplant cyclophosphamide

Author

Beatrice Mahe, Nicolas Blin, Alix Duquesne, Alice Garnier, Anne Lok, Pierre Peterlin, Marie C. Béné, Marion Eveillard, Amandine Le Bourgeois, Thomas Gastinne, Thierry Guillaume, Viviane Dubruille, Cyrille Touzeau, Philippe Moreau, Steven Le Gouill, Patrice Chevallier, and Benoit Tessoulin

Subjects
Adult, Male, medicine.medical_specialty, Transplantation Conditioning, CD3 Complex, Cyclophosphamide, Antigens, CD34, Context (language use), Gastroenterology, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Clofarabine, Aged, Retrospective Studies, Hematology, business.industry, Incidence (epidemiology), Graft Survival, Hematopoietic Stem Cell Transplantation, General Medicine, Middle Aged, Fludarabine, Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, Cohort, Female, business, Immunosuppressive Agents, Follow-Up Studies, 030215 immunology, medicine.drug
Abstract

The influence of peripheral blood stem cell (PBSC) graft cell contents after transplant with post-transplant cyclophosphamide (PTCY) remains unclear. Here, we retrospectively report on a cohort of 77 adults who received a Baltimore-based reduced-intensity conditioning regimen either with fludarabine (n = 40) or clofarabine (n = 37) and PTCY. With a median follow-up of 29.2 months, [2-]year overall (OS), disease-free (DFS), and GVHD/relapse-free survival (GRFS) rates were 62.8%, 51%, and 36.7%, respectively. The incidence of grades [2–]4 acute GVHD was significantly higher in patients transplanted with a haplodonor (n = 56), at 57.1% vs 19% (p = 0.006). PBSC graft cell contents (CD45+, CD34+, and CD3+ cells) had no impact on any outcome. Considering immune reconstitution until 1 year, only monocytes were above the normal range (as early as day + 30) during the first year post-transplant. In multivariate analysis, an older donor (> 45 years) and a high/very high disease risk index were independently associated with lower OS. A higher monocyte count (> median) at day + 90 was also associated with better OS, DFS, and GRFS. Donor/recipient CMV status matching was independently associated with GRFS. In conclusion, our data support the fact that there is no need to manipulate the graft before infusion in the particular context of PBSC/PTCY Baltimore-based allotransplant.

Published
2020

41. Impact on outcomes of mixed chimerism of bone marrow CD34+ sorted cells after matched or haploidentical allogeneic stem cell transplantation for myeloid malignancies

Author

Yannick Le Bris, Domitille Costes, Raphaël Bourgade, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Amandine Le Bourgeois, Patrice Chevallier, and Marie C. Béné

Subjects
Transplantation, Bone Marrow, Recurrence, Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Antigens, CD34, Hematology, Chimerism, Bone Marrow Transplantation
Abstract

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT), proposed to patients with high-risk myeloid malignancies, may ultimately fail because of disease relapse. Bone marrow (BM) CD34

Published
2022

42. B Cell Aplasia Is the Most Powerful Predictive Marker for Poor Humoral Response after BNT162b2 mRNA SARS-CoV-2 Vaccination in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

Author

Maxime Jullien, Amandine Le Bourgeois, Marianne Coste-Burel, Pierre Peterlin, Alice Garnier, Marie Rimbert, Berthe-Marie Imbert, Steven Le Gouill, Philippe Moreau, Beatrice Mahe, Viviane Dubruille, Nicolas Blin, Anne Lok, Cyrille Touzeau, Thomas Gastinne, Benoit Tessoulin, Sophie Vantyghem, Marie C. Béné, Thierry Guillaume, and Patrice Chevallier

Subjects
Transplantation, COVID-19 Vaccines, SARS-CoV-2, Vaccination, Hematopoietic Stem Cell Transplantation, COVID-19, Cell Biology, Hematology, CD8-Positive T-Lymphocytes, Molecular Medicine, Immunology and Allergy, Humans, RNA, Messenger, BNT162 Vaccine, Biomarkers
Abstract

Little is known about the immune response to SARS-CoV-2 vaccination in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, several studies have reported that adequate protection could be provided to this population. The purpose of this study was to evaluate which factors can predict the efficacy of SARS-CoV-2 vaccination in these specifically immunosuppressed patients. Specific anti-Spike (S) antibody responses were assessed in a cohort of 117 allo-HSCT recipients after 2 injections of BNT162b2 mRNA SARS-CoV-2 vaccine (V1 and V2). Factors considered liable to influence the antibody response and analyzed in this series were the interval between allo-HSCT and V1, donor source, recipient and donor age, current immunosuppressive/chemotherapy (I/C) treatment, and levels of CD4

Published
2021

43. Safety and antibody response after one and/or two doses of BNT162b2 Anti‐SARS‐CoV‐2 mRNA vaccine in patients treated by CAR T cells therapy

Author

Anne Lok, Pierre Peterlin, Viviane Dubruille, Steven Le Gouill, Sophie Vanthygem, Marianne Coste-Burel, Patrice Chevallier, Benoit Tessoulin, Berthe-Marie Imbert, Marie C. Béné, Nicolas Blin, Philippe Moreau, Thomas Drumel, Alice Garnier, Thierry Guillaume, Amandine Le Bourgeois, Beatrice Mahe, Maxime Jullien, Thomas Gastinne, Cyrille Touzeau, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), 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), Bernardo, Elizabeth, 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), and 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)

Subjects
Male, Antibodies, Viral, Immunotherapy, Adoptive, Immunogenicity, Vaccine, 0302 clinical medicine, vaccine, Antineoplastic Combined Chemotherapy Protocols, Medicine, CAR‐T cells, 030212 general & internal medicine, Antigens, Viral, ComputingMilieux_MISCELLANEOUS, Receptors, Chimeric Antigen, Lymphoma, Non-Hodgkin, Vaccination, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, SARS-CoV-2 mRNA, Combined Modality Therapy, 3. Good health, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, Female, Car t cells, COVID 19, Adult, 2019-20 coronavirus outbreak, Fever, Coronavirus disease 2019 (COVID-19), CAR-T cells, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunization, Secondary, Receptors, Antigen, T-Cell, Pain, [SDV.CAN]Life Sciences [q-bio]/Cancer, SARS‐CoV‐2 mRNA, Immunocompromised Host, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Correspondence, Humans, In patient, BNT162 Vaccine, Aged, Biological Products, Messenger RNA, SARS-CoV-2, business.industry, COVID-19, Virology, Antibody response, Immunoglobulin G, BNT162b2, business
Abstract

International audience; No abstract available

Published
2021

44. Safety and immunogenicity of a first dose of SARS‐CoV‐2 mRNA vaccine in allogeneic hematopoietic stem‐cells recipients

Author

Marie C. Béné, Philippe Moreau, Thomas Drumel, Sophie Vanthygem, Thomas Gastinne, Maxime Jullien, Amandine Le Bourgeois, Thierry Guillaume, Viviane Dubruille, Berthe-Marie Imbert, Cyrille Touzeau, Steven Le Gouill, Alice Garnier, Marianne Coste-Burel, Anne Lok, Pierre Peterlin, Patrice Chevallier, Beatrice Mahe, and Nicolas Blin

Subjects
Chemotherapy, business.industry, Immunogenicity, medicine.medical_treatment, Short Report, Transplantation, Vaccination, Haematopoiesis, Immunology, Medicine, Seroconversion, Stem cell, business, Prospective cohort study
Abstract

This was a monocentric prospective study testing the efficacy and safety of a first injection of BNT162b2 (Pfizer‐BioNTech) in 112 Allo‐HSCT patients. Antibody response to SARS‐CoV‐2 spike protein receptor‐binding domain was tested at the time of the second injection (Roche Elecsys). The study also included a non‐randomized control arm of 26 healthy controls. This study shows that a first dose of SARS‐CoV‐2 messenger RNA vaccine is safe and provides a 55% rate of seroconversion in allotransplanted patients compared to 100% for the controls (p

Published
2021

45. Impact of KIR/HLA Incompatibilities on NK Cell Reconstitution and Clinical Outcome after T Cell–Replete Haploidentical Hematopoietic Stem Cell Transplantation with Posttransplant Cyclophosphamide

Author

Dhon Roméo Makanga, Catherine Willem, Marie C. Béné, Alice Garnier, Thierry Guillaume, Katia Gagne, Anne Cesbron, Nolwenn Legrand, Christelle Retière, Bercelin Maniangou, Amandine Le Bourgeois, Patrice Chevallier, Pierre Peterlin, Bernardo, Elizabeth, Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), 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), Etablissement Français du Sang [Nantes], LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Service d'Hématologie Biologique [CHU Nantes], 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), and LabEx IGO 'Immunotherapy, Graft, Oncology' [Nantes]

Subjects
Adult, Male, Cyclophosphamide, medicine.medical_treatment, Immunology, Cell, Graft vs Leukemia Effect, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), Human leukocyte antigen, Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, Receptors, KIR, [SDV.CAN] Life Sciences [q-bio]/Cancer, HLA Antigens, medicine, Humans, Immunology and Allergy, Receptor, Aged, business.industry, Donor selection, Hematopoietic Stem Cell Transplantation, Middle Aged, 3. Good health, Killer Cells, Natural, Transplantation, Treatment Outcome, medicine.anatomical_structure, Blood Group Incompatibility, Transplantation, Haploidentical, Female, business, Immunosuppressive Agents, 030215 immunology, medicine.drug
Abstract

P.C. and C.R. have equally contributed to this work; International audience; Little is known regarding the effect of KIR/HLA incompatibilities (inc.) in the setting of T-replete haploidentical allogeneic he-matopoietic stem cell transplantation using posttransplant cyclophosphamide (PTCy). In this retrospective study, the impact of KIR/HLA inc. on clinical outcomes and NK cell reconstitution was studied in a cohort of 51 consecutive patients receiving a T cell-replete haploidentical allogeneic hematopoietic stem cell transplantation after a reduced-intensity conditioning using peripheral blood stem cells as the source of the graft and PTCy as graft-versus-host disease (GvHD) prophylaxis. The NK cell repertoire reconstitution was examined by multiparameter flow cytometry in 34 of these 51 patients from day 0 to day 100 post-transplant. Genetic KIR2DL/HLA inc. were found to be significantly associated with more GvHD (81.2 versus 45.7%, p = 0.01) and less relapse (6.2 versus 42.8%, p = 0.008) in this context. GvHD is associated with increased levels of differentiated and activated NK cells. A significant loss of KIR2DL2/3 + NK cells was observed at day 30 in patients with inhibitory KIR/HLA inc., suggesting that responsive KIR NK cells are particularly targeted by the immunosuppressive PTCy treatment. Further investigations are needed from a larger cohort with an identical clinical approach to consolidate these results and to identify the NK cell subsets that may be beneficial for the graft-versus-leukemia effect observed. Because many haploidentical donors can be identified in a family, the prediction of KIR NK cell alloreactivity could be of crucial importance for donor selection and patient outcome.

Published
2019

46. Gestion des toxicités des lymphocytes T exprimant un récepteur à l’antigène chimérique (CAR-T cells)

Author

Amandine Le Bourgeois, Service d'hématologie clinique, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)

Subjects
0301 basic medicine, Gynecology, Cancer Research, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], Hematology, General Medicine, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Medicine, Radiology, Nuclear Medicine and imaging, Car t cells, business
Abstract

Resume Les lymphocytes T exprimant un recepteur a l’antigene chimerique (CAR T-cells) representent une therapeutique innovante chez les patients atteints d’hemopathies malignes ou de cancers solides, avec de nombreux essais cliniques en cours. Les principales complications observees, apres leur injection, sont des syndromes de relargage cytokinique (SRC) et des complications neurologiques. Ces effets secondaires sont generalement reversibles, mais peuvent se compliquer et entrainer le deces du patient. L’objectif de cette revue est de decrire les manifestations clinico-biologiques observees apres l’injection de CAR T-cells, leur physiopathologie, ainsi que leur prise en charge. Cette derniere, ainsi que le traitement des complications viennent de faire l’objet de recommandations americaines au sein du groupe CARTOX (CAR T-cell-therapy-associated TOXicity working group), decrites dans cet article.

Published
2018

47. Allogreffe : nouveautés et perspectives

Author

Amandine Le Bourgeois

Subjects
03 medical and health sciences, Medical Laboratory Technology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Biochemistry (medical), 030215 immunology, Analytical Chemistry
Abstract

Resume Des recentes avancees dans le domaine de l’allogreffe de cellules souches hematopoietiques (allo-CSH) ont vu le jour, avec notamment le developpement des greffes a partir de donneurs familiaux semi-compatibles ou haplo-identiques. En effet, depuis quelques annees, les greffes haplo-identiques sont en pleine expansion grâce a l’utilisation de fortes doses d’en- doxan post-allogreffe permettant de favoriser la prise de greffe tout en reduisant les risques de reaction du greffon contre l’hote (GVH). Par ailleurs, l’amelioration des connaissances de la physiologie de la GVH ainsi que l’apparition de nouveaux traitements anti-infectieux, ont permis de reduire les risques de complications post-allogreffe. Malheureusement, la principale cause de mortalite apres allo-CSH reste le deces lie a la rechute de l’hemopathie initiale. La encore, des strategies d’immunotherapie preventive de la rechute sont mises en place depuis quelques annees avec des resultats tres encourageants. Nous evoquerons egalement le developpement de l’immunotherapie cellulaire avec les CAR T-cells, therapeutique qui pourrait challenger la place de l’allo-CSH dans le futur.

Published
2018

48. A novel complete blood count‐based score to screen for myelodysplastic syndrome in cytopenic patients

Author

Marie C. Béné, Marion Eveillard, Olivier Theisen, Camille Debord, Pierre Peterlin, Patrice Chevallier, Uwe Platzbecker, Amandine Le Bourgeois, Thierry Guillaume, Catherine Godon, Philippe Moreau, Yannick Le Bris, Frank Kroschinsky, Marouane Boubaya, Alice Garnier, Katja Sockel, and Robin Boutault

Subjects
Male, medicine.medical_specialty, Neutropenia, Pancytopenia, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, hemic and lymphatic diseases, Internal medicine, parasitic diseases, Overall survival, Humans, Medicine, In patient, Prospective Studies, Prospective cohort study, Mean corpuscular volume, Aged, Aged, 80 and over, Cytopenia, medicine.diagnostic_test, business.industry, Myelodysplastic syndromes, Complete blood count, Hematology, Middle Aged, medicine.disease, Thrombocytopenia, Blood Cell Count, Early Diagnosis, Case-Control Studies, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, Absolute neutrophil count, Female, business, 030215 immunology
Abstract

The diagnosis of myelodysplastic syndromes (MDS) is often challenging, time- and resource-consuming. A thorough analysis of complete blood count (CBC) parameters could, however, help to screen for MDS among other causes of cytopenia. To test this hypothesis, 109 newly-diagnosed MDS patients and 399 cytopenic patients older than 50 years with confirmed absence of MDS were enrolled in a prospective study. Multiparametric analysis highlighted three CBC parameters that were significantly different between the two cohorts: mean corpuscular volume, absolute neutrophil count and median neutrophil complexity and width of dispersion of the events measured (Ne-WX), which were used to define an MDS-CBC score. This score enables the prediction of MDS with 86% sensitivity and 88% specificity. The MDS-CBC score excluded MDS in 89% of cytopenic controls. Moreover, high score values at MDS diagnosis significantly correlated with decreased event-free (P = 0·02) and overall survival (P = 0·01). The power of this score was confirmed in an independent validation cohort (MDS n = 34, cytopenic controls n = 28). The MDS-CBC score is an easy and fast tool to exclude or suspect MDS in unselected patients with cytopenia of unknown reasons at the time of analysis, by prompting blood smear examination. It may thus improve allocation of further MDS-specific work-up in patients with cytopenia at the time of CBC assessment.

Published
2018

49. Interest of a third dose of BNT162b2 anti‐SARS‐CoV‐2 messenger RNA vaccine after allotransplant

Author

Philippe Moreau, Berthe-Marie Imbert, Thierry Guillaume, Steven Le Gouill, Marianne Coste-Burel, Thomas Gastinne, Amandine Le Bourgeois, Alice Garnier, Cyrille Touzeau, Maxime Jullien, Thomas Drumel, Nicolas Blin, Sophie Vantyghem, Benoit Tessoulin, Beatrice Mahe, Marie C. Béné, Anne Lok, Pierre Peterlin, Patrice Chevallier, Viviane Dubruille, Centre hospitalier universitaire de Nantes (CHU Nantes), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), 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), and Bernardo, Elizabeth

Subjects
Adult, Male, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV.CAN]Life Sciences [q-bio]/Cancer, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) mRNA, Antibodies, Viral, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, vaccine, Correspondence, Medicine, Humans, Transplantation, Homologous, BNT162 Vaccine, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, Messenger RNA, business.industry, SARS-CoV-2, COVID-19, allogeneic haematopoietic stem cell transplantation, Hematology, Organ Transplantation, Middle Aged, Allografts, Virology, Antibody Formation, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA, third dose, coronavirus disease 2019 (COVID-19), Female, BNT162b2, coronavirus disease 2019 (COVID‐19), business, Stem Cell Transplantation
Abstract

International audience; No abstract available

Published
2021

50. Diagnosis and prognosis are comforted by integrated assessment of next-generation sequencing in chronic myeloid malignancies. A real-life study

Author

Olivier Theisen, Pierre Peterlin, Viviane Dubruille, Patrice Chevallier, Pascal Godmer, Amandine Le Bourgeois, Sylvain Thepot, Anne Parcelier, Marion Loirat, Steven Le Gouill, Adrien Trebouet, Damien Luque Paz, Mélanie Mercier, S. Vigouroux, Mathilde Hunault, Céline Bossard, Marie C. Béné, Marion Eveillard, Audrey Ménard, Alice Garnier, Nadine Morineau, Camille Debord, Hervé Maisonneuve, François Subiger, Catherine Godon, Yannick Le Bris, Elsa Lestang, Jacques Delaunay, Sophie Vantyghem, Soraya Wuilleme, Anne Moreau, Ronan Le Calloch, Philippe Moreau, Lenaïg Le Clech, Thierry Guillaume, Bruno Villemagne, Valérie Ugo, Service d'Hématologie Clinique [CHU Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département d'Hématologie Clinique [CHU d'Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Hématologie Biologique [CHU Nantes], Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Hôpital privé du Confluent [Nantes], Hématologie clinique [CH La Roche-sur-Yon], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Laboratoire de Biologie [CHD Vendée, La Roche sur Yon], CHD Vendee (La Roche Sur Yon), Centre hospitalier de Saint-Nazaire, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Université de Bretagne Sud - Lorient (UBS Lorient), Université de Bretagne Sud (UBS), Laboratoire d'Hématologie Biologique (Hémato - ANGERS), Centre Hospitalier Intercommunal de Cornouaille [Quimper] (CHI Cornouaille [Quimper]), Département de Pathologie [CHU Nantes], Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), 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 Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), and Bernardo, Elizabeth

Subjects
Oncology, medicine.medical_specialty, Myeloid, Somatic cell, diagnosis, theranostic, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Group B, DNA sequencing, Article, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Neoplasms, medicine, Humans, 030304 developmental biology, 0303 health sciences, Myeloproliferative Disorders, business.industry, Myelodysplastic syndromes, Editorials, High-Throughput Nucleotide Sequencing, Hematology, Chronic Myeloproliferative Disorders, medicine.disease, Prognosis, somatic mutation by NGS, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Myelodysplastic Syndromes, Mutation, Bone marrow, business
Abstract

Next-generation sequencing (NGS) is used to investigate the presence of somatic mutations. The utility of incorporating routine sequencing to guide diagnosis and therapeutic decisions remains unclear. We report the findings of an observational, multicenter study that aimed to assess the impact of somatic mutation testing by NGS in a reallife setting of chronic myeloid malignancies. A total of 177 patients were enrolled, partitioned into two overlapping groups. In group A (n=94), the indication was to search for clonal hematopoiesis, in a context of suspected myelodysplastic syndrome or myeloproliferative neoplasia. In group B (n=95), the theranostic impact of somatic mutations was studied. A panel of 34 genes was used on DNA extracted from blood or bone marrow samples. Within group A, the detection of clonal hematopoiesis supported the diagnosis of chronic myeloid malignancies for 31 patients while the absence of clonal hematopoiesis ruled out the suspected diagnosis in 47 patients. Within group B, NGS identified prognostically relevant somatic mutations in 32 patients, which had a therapeutic impact in 18 cases. By determining the presence or absence of somatic mutations, the application of NGS in daily practice was found to be useful for an integrated final diagnosis in 83% of the patients. Moreover, the search for somatic mutations had a prognostic impact that led to treatment modification in 19% of the cases. This study outlines the fact that adequate implementation of new investigations may have a significant positive medico-economic impact by enabling appropriate management of patients.

Published
2021

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