{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T09:47:09Z","timestamp":1756460829486,"version":"3.41.2"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Mixed phenotype acute leukemia (MPAL) accounts for 2-5% of leukemia in children. MPAL are at higher risk of induction failure. Lineage switch (B to M or vice versa) or persistence of only the lymphoid or myeloid clone is frequently observed in biphenotypic\/bilineal cases, highlighting their lineage plasticity. The prognosis of MPAL remains bleak, with an event-free survival (EFS) of less than 50% in children. A lymphoid-type therapeutic approach appears to be more effective but failures to achieve complete remission (CR) remain significant. KMT2A fusions account for 75-80% of leukemia in infants under one year of age and remains a major pejorative prognostic factor in the Interfant-06 protocol with a 6 years EFS of only 36%. The search for other therapeutic approaches, in particular immunotherapies that are able to eradicate all MPAL clones, is a major issue. We describe here the feasibility and tolerance of the combination of two targeted immunotherapies, blinatumomab and Gemtuzumab Ozogamicin, in a 4-year-old infant with a primary refractory KTM2A-rearranged MPAL. Our main concern was to determine how to associate these two immunotherapies and we describe how we decided to do it with the parents\u2019 agreement. The good MRD response on the two clones made it possible to continue the curative intent with a hematopoietic stem cell transplant at 9 months of age. Despite a relapse at M11 post-transplant because of the recurrence of a pro-B clone retaining the initial lymphoid phenotype, the child is now 36 months old, in persistent negative MRD CR2 for 12 months after a salvage chemotherapy and an autologous CAR T cells infusion, with no known sequelae to date. This case study can thus lead to the idea of a sequential combination of two immunotherapies targeting two distinct leukemic subclones (or even a single biphenotypic clone), as a potential one to be tested prospectively in children MPAL and even possibly all KMT2A-rearranged infant ALL.<\/jats:p>","DOI":"10.3389\/fonc.2021.637951","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T15:03:16Z","timestamp":1614351796000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Case Report: Targeting 2 Antigens as a Promising Strategy in Mixed Phenotype Acute Leukemia: Combination of Blinatumomab With Gemtuzumab Ozogamicin in an Infant With a KMT2A-Rearranged Leukemia"],"prefix":"10.3389","volume":"11","author":[{"given":"Beno\u00eet","family":"Brethon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elodie","family":"Lainey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lie","family":"Caye-Eude","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Grain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Odile","family":"Fenneteau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karima","family":"Yakouben","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Roupret-Serzec","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lou","family":"Le Mouel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Cav\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Baruchel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.014506","article-title":"Prognosis of children with mixed phenotype acute leukemia on the basis of consistent immunophenotypic criteria","volume":"95","author":"Mejstrikova","year":"2010","journal-title":"Haematologica"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.007799","article-title":"Biphenotypic, bilineal, ambiguous or mixed lineage: strange leukemias","volume":"94","author":"B\u00e9n\u00e9","year":"2009","journal-title":"Haematologica"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-209262","article-title":"The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes","volume":"114","author":"Vardiman","year":"2009","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-187351","article-title":"Acute mixed lineage leukemia in children: the experience of St Jude Children\u2019s Research Hospital","volume":"113","author":"Rubnitz","year":"2009","journal-title":"Blood"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-12-821363","article-title":"International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia","volume":"132","author":"Hrusak","year":"2018","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/ejh.13413","article-title":"Mixed phenotype acute leukemia: Biological profile, clinical characteristic and treatment outcomes: Report of the population-based study","volume":"105","author":"Zaj\u0105c-Spycha\u0142a","year":"2020","journal-title":"Eur J Haematol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.00261","article-title":"Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results from an International Phase III Randomized Study","volume":"37","author":"Pieters","year":"2019","journal-title":"J Clin Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004008","article-title":"Blinatumomab for infant acute lymphoblastic leukemia","volume":"135","author":"Clesham","year":"2020","journal-title":"Blood"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.67.3301","article-title":"Phase I\/phase II study of blinatumomab in pediatric patients with relapsed\/refractory acute lymphoblastic leukemia","volume":"34","author":"von Stackelberg","year":"2016","journal-title":"J Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0770-8","article-title":"Blinatumomab versus historical standard therapy in pediatric patients with relapsed\/refractory Ph-negative B-cell precursor acute lymphoblastic leukemia","volume":"34","author":"Locatelli","year":"2020","journal-title":"Leukemia"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.55.3628","article-title":"Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children\u2019s Oncology Group trial AAML0531","volume":"32","author":"Gamis","year":"2014","journal-title":"J\u00a0Clin Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-01-762336","article-title":"Gemtuzumab ozogamicin in infants with AML: results from the Children\u2019s Oncology Group trials AAML03P1 and AAML0531","volume":"130","author":"Guest","year":"2017","journal-title":"Blood"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07370.x","article-title":"Efficacy of fractionated gemtuzumab ozogamicin with cytarabine in advanced childhood leukaemia","volume":"143","author":"Brethon","year":"2008","journal-title":"Br J Haematol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.637951\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T15:03:17Z","timestamp":1614351797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2021.637951\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,26]]},"references-count":14,"alternative-id":["10.3389\/fonc.2021.637951"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2021.637951","relation":{},"ISSN":["2234-943X"],"issn-type":[{"type":"electronic","value":"2234-943X"}],"subject":[],"published":{"date-parts":[[2021,2,26]]},"article-number":"637951"}}