Prognostic impact of FLT3 -ITD microclones in young adults with acute myeloid leukemia treated with intensive chemotherapy
Year: 2026
Type: article
Abstract: ABSTRACT: FLT3 internal tandem duplications (FLT3-ITD) are major genetic events in acute myeloid leukemia (AML). Although the clinical impact of FLT3-ITD "macroclones" (allelic ratio [AR] ≥0.05) is well established, the significance of low-level FLT3-ITD subclones ("microclones") remains uncertain. We conducted a post hoc analysis of 1733 patients with newly diagnosed AML enrolled in the Backbone Intergroup 1 trial (ClinicalTrials.gov identifier: NCT02416388). Using next-generation sequencing (NGS), we detected FLT3-ITD microclones (AR between 0.0004 and 0.05) in 17.4% of patients without FLT3-ITD macroclones. Microclones and macroclones (low and high AR) were independently associated with increased relapse risk (cause-specific hazard ratio, 1.50 [95% confidence interval (CI), 1.18-1.91]; 1.98 [1.50-2.62]; and 2.33 [1.69-3.22], respectively) after adjustment for age, white blood cell count, other gene mutations, midostaurin treatment, and allogeneic hematopoietic stem cell transplantation. At 2 years, the cumulative incidence of relapse reached 42.5% (95% CI, 37.0-47.9) in patients with macroclones, 45.1% (38.3-51.6) in patients with microclones, and 29.4% (26.6-32.3) in patients without FLT3-ITD. In NPM1-mutated AML, both microclones and macroclones were associated with higher levels of measurable residual disease (MRD) and increased relapse risk, without independent impact on overall survival after adjustment for MRD. An analysis of paired samples further revealed that 41.8% of relapses in patients with FLT3-ITD microclones at diagnosis were associated with a macroclone at relapse. These findings challenge current risk stratification models and support the integration of NGS-based FLT3-ITD detection into the diagnostic and prognostic workflow for AML. Prospective trials addressing the management of patients with FLT3-ITD microclones are warranted, as is their consideration in future European LeukemiaNet guidelines.
Source: Blood
Authors: Nicolas Duployez, Romane Joudinaud, Augustin Boudry, Mathilde Hunault, Laurène Fenwarth, Emmanuelle Tavernier, Cécile Pautas, Sarah Bertoli, Suzanne Tavitian, Emmanuel Raffoux, Tony Marchand, Maël Heiblig, Sylvain Chantepie, Martin Carre, Pierre Peterlin, Maria-Pilar Gallego-Hernanz, Romain Guieze, Célestine Simand, Pascal Turlure, Anne Huynh, Emilie Lemasle, Ludovic Gabellier, Juliette Lambert, Felipe Suarez, Samy Chraibi, Laurence Sanhes, Karine Celli-Lebras, Ariane Mineur, Claude Gardin, Norbert Ifrah, Norbert Vey, Régis Peffault De Latour, Lucie Rigolot, Isabelle Luquet, Dominique Penther, Raphaël Itzykson, Éric Delabesse, Jean-François Hamel, Stéphane De Botton, Arnaud Pigneux, Hervé Dombret, Christian Récher, Claude Preudhomme, Pierre-Yves Dumas
Institutions: Inserm, Université de Lille, Centre Hospitalier Universitaire de Lille, Centre National de la Recherche Scientifique, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers, Centre Hospitalier Universitaire d'Angers, Université de Nantes, Université d'Angers, Nantes Université, Centre Hospitalier Universitaire de Saint-Étienne, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Henri-Mondor, Centre Hospitalier Universitaire de Toulouse, Université Paris Cité, Hôpital Saint-Louis, Centre Hospitalier Universitaire de Rennes, Hospices Civils de Lyon, Centre Hospitalier Universitaire de Caen Normandie, Centre Hospitalier Universitaire de Grenoble, Centre Hospitalier Universitaire de Nantes, Centre Hospitalier Universitaire de Poitiers, Centre Hospitalier Universitaire de Clermont-Ferrand, Hôpitaux Universitaires de Strasbourg, Centre Hospitalier Universitaire de Limoges, Centre Henri Becquerel, Centre Hospitalier Universitaire de Montpellier, Centre Hospitalier de Versailles, Hôpital Necker-Enfants Malades, Centre Hospitalier Universitaire de Nîmes, Centre Hospitalier de Perpignan, Acute Leukemia French Association, Université Sorbonne Paris Nord, Hôpital Avicenne, Laboratoire d'hématologie, Institut Paoli-Calmettes, Institut Gustave Roussy, Centre Hospitalier Universitaire de Bordeaux
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,500
OpenAlex ID: W7161980234