{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T03:38:05Z","timestamp":1791430685826,"version":"4.3.3"},"reference-count":15,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:sec id=\"ab-cbr240008-4\"><jats:title>Importance<\/jats:title><jats:p>Persistence of <jats:italic>FLT3<\/jats:italic> internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown.<\/jats:p><\/jats:sec><jats:sec id=\"ab-cbr240008-5\"><jats:title>Objective<\/jats:title><jats:p>To examine the association between pre\u2013allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR.<\/jats:p><\/jats:sec><jats:sec id=\"ab-cbr240008-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>In this cohort study, DNA sequencing was performed on first CR blood from patients with <jats:italic>FLT3<\/jats:italic>-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023.<\/jats:p><\/jats:sec><jats:sec id=\"ab-cbr240008-7\"><jats:title>Exposure<\/jats:title><jats:p>Centralized DNA sequencing for <jats:italic>FLT3<\/jats:italic>-ITD in pre\u2013allogeneic HCT first CR blood using a commercially available kit.<\/jats:p><\/jats:sec><jats:sec id=\"ab-cbr240008-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary outcomes were overall survival and cumulative incidence of relapse, with non\u2013relapse-associated mortality as a competing risk post\u2013allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points.<\/jats:p><\/jats:sec><jats:sec id=\"ab-cbr240008-9\"><jats:title>Results<\/jats:title><jats:p>Of 537 included patients with <jats:italic>FLT3<\/jats:italic>-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 <jats:italic>FLT3<\/jats:italic>-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual <jats:italic>FLT3<\/jats:italic>-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning.<\/jats:p><\/jats:sec><jats:sec id=\"ab-cbr240008-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>This study provides generalizable and clinically applicable evidence that the detection of residual <jats:italic>FLT3<\/jats:italic>-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2024.0985","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T15:32:35Z","timestamp":1714663955000},"page":"1104","source":"Crossref","is-referenced-by-count":69,"title":["Measurable Residual <i>FLT3<\/i> Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia"],"prefix":"10.1001","volume":"10","author":[{"given":"Laura W.","family":"Dillon","sequence":"first","affiliation":[{"name":"Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gege","family":"Gui","sequence":"additional","affiliation":[{"name":"Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niveditha","family":"Ravindra","sequence":"additional","affiliation":[{"name":"Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Andrew","sequence":"additional","affiliation":[{"name":"Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devdeep","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00eb C.","family":"Wong","sequence":"additional","affiliation":[{"name":"Laboratory of Myeloid Malignancies, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Huang","sequence":"additional","affiliation":[{"name":"Invivoscribe, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Gerhold","sequence":"additional","affiliation":[{"name":"Invivoscribe, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Holman","sequence":"additional","affiliation":[{"name":"Invivoscribe, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Invivoscribe, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Miller","sequence":"additional","affiliation":[{"name":"Invivoscribe, San Diego, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jake","family":"Higgins","sequence":"additional","affiliation":[{"name":"TwinStrand Biosciences, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse J.","family":"Salk","sequence":"additional","affiliation":[{"name":"TwinStrand Biosciences, Seattle, Washington"},{"name":"University of Washington School of Medicine, Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery J.","family":"Auletta","sequence":"additional","affiliation":[{"name":"Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota"},{"name":"The Ohio State University College of Medicine, Columbus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firas","family":"El Chaer","sequence":"additional","affiliation":[{"name":"University of Virginia, Charlottesville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Devine","sequence":"additional","affiliation":[{"name":"Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Martin","family":"Jimenez-Jimenez","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, Miami, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos J. 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