{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T03:47:25Z","timestamp":1793850445582,"version":"4.6.1"},"reference-count":73,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,24]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Lineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic leukemia (B-ALL) transforming to acute myeloid leukemia (AML), 17 (22.7%) cases of B-ALL transforming to mixed phenotypic acute leukemia (MPAL)\/acute leukemias of ambiguous lineage (ALAL), and 5 (6.7%) cases of rare LS presentation (ie, T-cell ALL to AML). An additional 10 cases with incomplete changes in immunophenotype, referred to as \u201clineage drift\u201d were also described. With a primary focus on the 70 cases of LS from B-ALL to AML or MPAL\/ALAL, LS emerged at a median of 1.5 months (range, 0-36.5) after immunotherapy, with 81.4% presenting with LS within the first 6 months from the most proximal immunotherapy. Although most involved KMT2A rearrangements (n = 45, 64.3%), other rare cytogenetic and\/or molecular alterations were uniquely observed. Treatment outcomes were generally poor, with remission rates of &amp;lt;40%. The median overall survival after LS diagnosis was 4.8 months. Outcomes were similarly poor for those with rare immunophenotypes of LS or lineage drift. This global initiative robustly categorizes lineage changes after immunotherapy and, through enhanced understanding, establishes a foundation for improving outcomes of LS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024026655","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T16:12:59Z","timestamp":1744042379000},"page":"437-455","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":53,"title":["Project EVOLVE: an international analysis of postimmunotherapy lineage switch, an emergent form of relapse in leukemia"],"prefix":"10.1182","volume":"146","author":[{"given":"Sara K.","family":"Silbert","sequence":"first","affiliation":[{"name":"1Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6089-9279","authenticated-orcid":false,"given":"Alexander W.","family":"Rankin","sequence":"additional","affiliation":[{"name":"1Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe N.","family":"Hoang","sequence":"additional","affiliation":[{"name":"1Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7082-1694","authenticated-orcid":false,"given":"Alexandra","family":"Semchenkova","sequence":"additional","affiliation":[{"name":"2Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2542-2061","authenticated-orcid":false,"given":"Regina M.","family":"Myers","sequence":"additional","affiliation":[{"name":"3Department of Pediatrics and the Center for Childhood Cancer Research, Children\u2019s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9634-5828","authenticated-orcid":false,"given":"Elena","family":"Zerkalenkova","sequence":"additional","affiliation":[{"name":"4Laboratory of Cytogenetics and Molecular Genetics, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5408-9253","authenticated-orcid":false,"given":"Hao-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"5Flow Cytometry Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6742-6749","authenticated-orcid":false,"given":"Alexandra E.","family":"Kovach","sequence":"additional","affiliation":[{"name":"6Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA"},{"name":"70Keck School of Medicine, University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2601-3665","authenticated-orcid":false,"given":"Constance M.","family":"Yuan","sequence":"additional","affiliation":[{"name":"5Flow Cytometry Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Delgado Colon","sequence":"additional","affiliation":[{"name":"5Flow Cytometry Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9065-0477","authenticated-orcid":false,"given":"Lo\u00efc","family":"Vasseur","sequence":"additional","affiliation":[{"name":"7Adolescent and Young Adult Hematology Unit, Saint Louis University Hospital, Assistance Publique H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Bataller","sequence":"additional","affiliation":[{"name":"8Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"John","sequence":"additional","affiliation":[{"name":"9Division of Pediatric Hematology-Oncology, Harold C. 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