{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:39:44Z","timestamp":1789011584393,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health\u2014Current research IRCSS"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Blinatumomab (Blina) and inotuzumab ozogamicin (InO) has improved the outcome of relapsed\/refractory B-lymphoblastic leukemia (R\/R B-ALL). However, little is known about the outcome after recurrence and re-treatment with immunotherapy. Methods: We describe 71 R\/R B-ALL patients treated for different relapses with Blina and InO. Blina was the first treatment in 57 patients and InO in 14. Twenty-seven patients had a previous allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: In the Blina\/InO group, after Blina, 36 patients (63%) achieved a complete remission (CR), with 42% of negative minimal residual disease (MRD\u2212); after InO, a CR was achieved in 47 patients (82%, 34 MRD\u2212). In the InO\/Blina group, after InO, 13 cases (93%) reached a CR (6 MRD\u2212); after Blina, a CR was re-achieved in 6 cases (43%, 3 MRD\u2212). Twenty-six patients proceeded to allo-HSCT. In the Blina\/InO group, the median overall survival (OS) was 19 months; the disease-free survival (DFS) after Blina was 7.4 months (11.6 vs. 2.7 months in MRD\u2212 vs. MRD+, p = 0.03) and after InO, 5.4 months. In the InO\/Blina group, the median OS was 9.4 months; the median DFS after InO was 5.1 months and 1.5 months after Blina (8.7 vs. 2.5 months in MRD\u2212 vs. MRD+, p = 0.02). With a median follow-up of 16.5 months from the start of immunotherapy, 24 patients (34%) are alive and 16 (22%) are alive in CR. Conclusion: In our series of R\/R B-ALL, Blina and InO treatment demonstrate efficacy for subsequent relapses in terms of MRD response, OS and DFS, and as a bridge to allo-HSCT.<\/jats:p>","DOI":"10.3390\/cancers15184623","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T02:47:52Z","timestamp":1695091672000},"page":"4623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Blinatumomab and Inotuzumab Ozogamicin Sequential Use for the Treatment of Relapsed\/Refractory Acute Lymphoblastic Leukemia: A Real-Life Campus All Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8982-8079","authenticated-orcid":false,"given":"Nicola Stefano","family":"Fracchiolla","sequence":"first","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7958-4966","authenticated-orcid":false,"given":"Mariarita","family":"Scium\u00e8","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Papayannidis","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cL. & A. Ser\u00e0gnoli\u201d, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Vitale","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Chiaretti","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9993-947X","authenticated-orcid":false,"given":"Mario","family":"Annunziata","sequence":"additional","affiliation":[{"name":"Hematology Unit, Azienda Ospedaliera Cardarelli, 11411 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Giglio","sequence":"additional","affiliation":[{"name":"Division of Onco-Hematology, European Institute of Oncology, IRCCS, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prassede","family":"Salutari","sequence":"additional","affiliation":[{"name":"Hematology Unit, Ospedale Civile Santo Spirito, 65100 Pescara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Forghieri","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Section of Hematology, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7568-9656","authenticated-orcid":false,"given":"Davide","family":"Lazzarotto","sequence":"additional","affiliation":[{"name":"Division of Hematology, University Hospital-ASUFC, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monia","family":"Lunghi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine, AOU Maggiore della Carit\u00e0, Universit\u00e0 del Piemonte Orientale, 13100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Imovilli","sequence":"additional","affiliation":[{"name":"Hematology Unit, Azienda Unit\u00e0 Sanitaria Locale-IRCCS, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Scappini","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Experimental and Clinical Medicine, Azienda Ospedaliero-Universitaria Careggi, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0716-1686","authenticated-orcid":false,"given":"Massimiliano","family":"Bonifacio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Hematology, University of Verona, 37129 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelina","family":"Dargenio","sequence":"additional","affiliation":[{"name":"Hematology and Stem Cell Transplantation Unit, Vito Fazzi Hospital, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Gurrieri","sequence":"additional","affiliation":[{"name":"Dipartimento Strutturale Aziendale Medicina, University of Padova, 35122 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Todisco","sequence":"additional","affiliation":[{"name":"Ospedale di Busto Arsizio, ASST Valle Olona, 21052 Busto Arsizio, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Defina","sequence":"additional","affiliation":[{"name":"Hematology Unit, University of Siena, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3958-0669","authenticated-orcid":false,"given":"Maria Ilaria","family":"Del Principe","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Biomedicina and Prevention, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Zappasodi","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology, Division of Hematology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-3100","authenticated-orcid":false,"given":"Marco","family":"Cerrano","sequence":"additional","affiliation":[{"name":"Division of Hematology, A.O.U. Citt\u00e0 della Salute e della Scienza, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Santoro","sequence":"additional","affiliation":[{"name":"Struttura Complessa di Ematologia e Trapianto Emopoietico, A.O.S.G. Moscati, 83100 Avellino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tagliaferri","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4085-5225","authenticated-orcid":false,"given":"Enrico","family":"Barozzi","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"De Roberto","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Canzi","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3478-5083","authenticated-orcid":false,"given":"Elisa","family":"Buzzatti","sequence":"additional","affiliation":[{"name":"Hematology Unit, Department of Biomedicina and Prevention, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2356-5691","authenticated-orcid":false,"given":"Chiara","family":"Sartor","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cL. & A. Ser\u00e0gnoli\u201d, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-5289","authenticated-orcid":false,"given":"Francesco","family":"Passamonti","sequence":"additional","affiliation":[{"name":"Hematology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Fo\u00e0","sequence":"additional","affiliation":[{"name":"Hematology, Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Curti","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cL. & A. Ser\u00e0gnoli\u201d, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"key":"ref_1","unstructured":"National Cancer Institute (2023, March 15). Cancer Stat Facts: Leukemia\u2014Acute Lymphocytic Leukemia (ALL), Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/alyl.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1200\/JCO.2017.77.3648","article-title":"New approaches to the management of adult acute lymphoblastic leukemia","volume":"36","author":"Bassan","year":"2018","journal-title":"J. Clin. 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Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1182\/blood.V126.23.679.679","article-title":"Complete molecular and hematologic response in adult patients with relapsed\/refractory (R\/R) Philadelphia chromosome\u2013positive B-precursor acute lymphoblastic leukemia (ALL) following treatment with blinatumomab: Results from a phase 2 single-arm, multicenter study (ALCANTARA)","volume":"126","author":"Martinelli","year":"2015","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.2217\/imt.15.108","article-title":"Role of inotuzumab ozogamicin in the treatment of relapsed\/refractory acute lymphoblastic leukemia","volume":"8","author":"George","year":"2016","journal-title":"Immunotherapy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6119","DOI":"10.1182\/blood-2022-157937","article-title":"Gimema ALL2418: Interim Analysis of a Phase IIa Study of Feasibility and Effectiveness of Inotuzumab Ozogamicin in Adult Patients with B-Cell Acute Lymphoblastic Leukemia with Positive Minimal Residual Disease before Any Hematopoietic Stem Cell Transplantation","volume":"140","author":"Marconi","year":"2022","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S101","DOI":"10.1016\/j.bbmt.2019.12.604","article-title":"Clinical outcome with allogeneic hematopoietic stem cell transplantation after blinatumomab or inotuzumab ozogamicin in patients with B-cell acute lymphoblastic leukemia: Real world experience","volume":"26","author":"Badar","year":"2020","journal-title":"Biol. Blood Marrow. Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.clml.2020.03.004","article-title":"Real world outcomes of adult B-cell acute lymphocytic leukemia patients treated with inotuzumab ozogamicin","volume":"20","author":"Badar","year":"2020","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13045-023-01444-2","article-title":"Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia","volume":"16","author":"Kantarjian","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13045-023-01409-5","article-title":"The evolution of acute lymphoblastic leukemia research and therapy at MD Anderson over four decades","volume":"16","author":"Jabbour","year":"2023","journal-title":"J. Hematol. 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Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/18\/4623\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:53:22Z","timestamp":1760129602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/18\/4623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,19]]},"references-count":31,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cancers15184623"],"URL":"https:\/\/doi.org\/10.3390\/cancers15184623","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,19]]}}}