{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:31:45Z","timestamp":1793316705895,"version":"4.5.0"},"reference-count":49,"publisher":"American Society of Hematology","issue":"21","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,11,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>KMT2A-rearranged (KMT2A-r) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is widely recognized as a high-risk leukemia in both children and adults. However, there is a paucity of data on adults treated in recent protocols, and the optimal treatment strategy for these patients is still a matter of debate. In this study, we set out to refine the prognosis of adult KMT2A-r BCP-ALL treated with modern chemotherapy regimen and investigate the prognostic impact of comutations and minimal residual disease (MRD). Of 1091 adult patients with Philadelphia-negative BCP-ALL enrolled in 3 consecutive trials from the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL), 141 (12.9%) had KMT2A-r, with 5-year cumulative incidence of relapse (CIR) and overall survival (OS) rates of 40.7% and 53.3%, respectively. Molecular profiling highlighted a low mutational burden in this subtype, reminiscent of infant BCP-ALL. However, the presence of TP53 and\/or IKZF1 alterations defined a subset of patients with significantly poorer CIR (69.3% vs 36.2%; P\u00a0= .001) and OS (28.1% vs 60.7%; P\u00a0= .006) rates. Next, we analyzed the prognostic implication of MRD measured after induction and first consolidation, using both immunoglobulin (IG) or T-cell receptor (TR) gene rearrangements and KMT2A genomic fusion as markers. In approximately one-third of patients, IG\/TR rearrangements were absent or displayed clonal evolution during the disease course, compromising MRD monitoring. In contrast, KMT2A-based MRD was highly reliable and strongly associated with outcome, with early good responders having an excellent outcome (3-year CIR, 7.1%; OS, 92.9%). Altogether, our study reveals striking heterogeneity in outcomes within adults with KMT2A-r BCP-ALL and provides new biomarkers to guide risk-based therapeutic stratification.<\/jats:p>","DOI":"10.1182\/blood.2023021501","type":"journal-article","created":{"date-parts":[[2023,8,18]],"date-time":"2023-08-18T17:05:02Z","timestamp":1692378302000},"page":"1806-1817","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":35,"title":["Genetic alterations and MRD refine risk assessment for\n                    <i>KMT2A<\/i>\n                    -rearranged B-cell precursor ALL in adults: a GRAALL study"],"prefix":"10.1182","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-7237","authenticated-orcid":false,"given":"Rathana","family":"Kim","sequence":"first","affiliation":[{"name":"1Hematology Laboratory, Saint-Louis Hospital, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"},{"name":"2INSERM U944, CNRS UMR 7212 GenCellDis, Institut de Recherche Saint-Louis, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8362-7460","authenticated-orcid":false,"given":"Hugo","family":"Bergugnat","sequence":"additional","affiliation":[{"name":"2INSERM U944, CNRS UMR 7212 GenCellDis, Institut de Recherche Saint-Louis, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5675-3154","authenticated-orcid":false,"given":"C\u00e9dric","family":"Pastoret","sequence":"additional","affiliation":[{"name":"3Hematology Laboratory, Centre Hospitalier Universitaire de Rennes, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Pasquier","sequence":"additional","affiliation":[{"name":"4Department of Hematology, Gustave Roussy Cancer Campus, Universit\u00e9 Paris-Saclay, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Raffoux","sequence":"additional","affiliation":[{"name":"5Hematology Department, Saint-Louis Hospital, Assistance Publique-H\u00f4pitaux de Paris, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9461-0728","authenticated-orcid":false,"given":"Lise","family":"Larcher","sequence":"additional","affiliation":[{"name":"1Hematology Laboratory, Saint-Louis Hospital, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"},{"name":"2INSERM U944, CNRS UMR 7212 GenCellDis, Institut de Recherche Saint-Louis, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4620-8782","authenticated-orcid":false,"given":"Marie","family":"Passet","sequence":"additional","affiliation":[{"name":"1Hematology Laboratory, Saint-Louis Hospital, Assistance Publique-H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6573-1312","authenticated-orcid":false,"given":"Nathalie","family":"Grardel","sequence":"additional","affiliation":[{"name":"6Hematology Laboratory, Centre Hospitalier R\u00e9gional Universitaire de Lille, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-0753","authenticated-orcid":false,"given":"Eric","family":"Delabesse","sequence":"additional","affiliation":[{"name":"7Hematology Laboratory, Institut Universitaire de Cancer Toulouse-Oncopole, INSERM 1037, CNRS, Universit\u00e9 Toulouse III-Paul Sabatier, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7604-4227","authenticated-orcid":false,"given":"Susanne","family":"Kubetzko","sequence":"additional","affiliation":[{"name":"8Department of Hematology, University Hospital of Z\u00fcrich, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5996-3037","authenticated-orcid":false,"given":"Aur\u00e9lie","family":"Caye-Eude","sequence":"additional","affiliation":[{"name":"9Genetics Department, Molecular Genetics Unit, H\u00f4pital Robert Debr\u00e9, Assistance Publique-H\u00f4pitaux de Paris, INSERM UMR_S1131, Institut de Recherche Saint-Louis, Universit\u00e9 de Paris-Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Meyer","sequence":"additional","affiliation":[{"name":"10Institute of Pharmaceutical Biology\/Diagnostic Center of Acute Leukemia, Goethe University, Frankfurt\/Main, 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