{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:46:46Z","timestamp":1784216806100,"version":"3.55.0"},"reference-count":17,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"14","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2017,5,10]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Erythroid response to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients experiencing ESA failure, 653 experienced primary failure and 494 experienced relapse after a response. Primary failure of ESAs was associated with a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS difference. Of 450 patients (39%) who received second-line treatment, 194 received HMAs, 148 received LEN, and 108 received other treatments (MISC), whereas 697 received RBC transfusions only. Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for those receiving HMAs, LEN, and MISC, respectively ( P = .05). Five-year OS for patients receiving HMA, LEN, and MISC was 36.5%, 41.7%, and 51%, respectively ( P = .21). In a multivariable analysis adjusted for age, sex, revised International Prognostic Scoring System score, and progression at ESA failure, there was no significant OS difference among the three groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this large, multicenter, retrospective cohort of patients with non-del(5q) lower-risk MDS treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure of ESAs was associated with a higher risk of AML progression.<\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2016.71.3271","type":"journal-article","created":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T19:55:52Z","timestamp":1490730952000},"page":"1591-1597","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":91,"title":["Outcome of Lower-Risk Patients With Myelodysplastic Syndromes Without 5q Deletion After Failure of Erythropoiesis-Stimulating Agents"],"prefix":"10.1200","volume":"35","author":[{"given":"Sophie","family":"Park","sequence":"first","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Hamel","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Toma","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charikleia","family":"Kelaidi","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Th\u00e9pot","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Diez","family":"Campelo","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Santini","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkael A.","family":"Sekeres","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Balleari","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Kaivers","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Sapena","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"G\u00f6tze","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catharina","family":"M\u00fcller-Thomas","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odile","family":"Beyne-Rauzy","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aspasia","family":"Stamatoullas","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Kotsianidis","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Komrokji","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Steensma","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Fensterl","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail J.","family":"Roboz","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Bernal","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; Rosa Sapena and Pierre Fenaux, CHU Saint Louis, AP-HP, Universit\u00e9 Paris X; Fran\u00e7ois Dreyfus, CHU Cochin, AP-HP,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Ramos","sequence":"additional","affiliation":[{"name":"Sophie Park, Centre Hospitalier Universitaire (CHU) Grenoble Alpes, Universit\u00e9 Grenoble Alpes, Grenoble; Jean-Fran\u00e7ois Hamel and Sylvain Th\u00e9pot, CHU d\u2019Angers; Sylvain Th\u00e9pot, Universit\u00e9 d\u2019Angers, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 1232, and LabEx IGO, Angers; Andrea Toma, CHU Henri Mondor, Assistance Publique H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil; 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