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A revised prognostic model for patients with acute myeloid leukemia and first relapse

van der Maas, N. G.
Breems, D.
Klerk, C. P. W.
Pabst, T.
Gradowska, P.
Thomas, A.
Biemond, B. J.
Kuball, J.
Van Elssen, C.
Visser, O.
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Abstract
Most patients with acute myeloid leukemia (AML) may obtain remission upon induction chemotherapy, but relapse is frequent and associated with poor survival. Previous prognostic models for outcomes after relapse lacked analysis of comprehensive molecular data. A validated prognostic model integrating clinical, cytogenetic, and molecular variables may support treatment decisions. We studied 943 patients with AML who relapsed after intensive induction treatment in a development cohort (HOVON-SAKK). A random survival forest algorithm was used to evaluate the association of clinical parameters, cytogenetic abnormalities, and molecular variables at diagnosis with overall survival (OS). Relapsing patients (n = 377) who were enrolled in the NCRI-AML18 trial were used for validation. In the development cohort, the median age at relapse was 58 years, and patients were classified as 2022 European LeukemiaNet favorable (22%), intermediate (31%), and adverse risk (48%). One-third underwent allogeneic transplantation in the first complete remission. Variable selection yielded 9 variables associated with 1-year OS, including relapse-free interval, age, white blood cell count, mutated TP53, FLT3 internal tandem duplication, core-binding factor abnormalities, t(v;11q23)/KMT2A rearrangement, and complex/monosomal karyotype, which were assigned points according to their estimated hazard ratios. Three prognostic groups were defined with distinct 1-year OS in both development (favorable, 51% ± 3%; intermediate, 29% ± 3%; and poor, 14% ± 2%, respectively) and validation cohorts (51% ± 4%, 26% ± 5%, and 14% ± 3%, respectively). Validation confirmed the improved accuracy in predicting outcomes for patients with AML in first relapse. The revised AML relapse model improved on previous prognostic models for outcomes after first relapse. It provides stratification that might support tailoring second line treatment.
Affiliation
Department of Hematology, Erasmus University Medical Center Cancer Institute, Rotterdam, The Netherlands. Department of Hematology, Ziekenhuis aan de Stroom, Cadix Hospital, Antwerp, Belgium. Department of Internal Medicine, Dijklander Hospital, Amsterdam, The Netherlands. Department of Medical Oncology, University Hospital, Inselspital, Bern, Switzerland. Swiss Group for Clinical Cancer Research, SAKK, Bern, Switzerland. HOVON Foundation, Rotterdam, The Netherlands. Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University, Cardiff, United Kingdom. Department of Hematology, Amsterdam University Medical Center, Cancer Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands. Department of Hematology, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands. Division Hematology, Department of Internal Medicine, GROW institute for Oncology and developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands. Department of Hematology, Isala Hospital, Zwolle, The Netherlands. Department of Hematology, Cliniques Universitaires Saint-Luc, Brussels, Belgium. Department of Hematology, Université Catholique de Louvain, University Hospital Center Namur (Godinne), Yvoir, Belgium. Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium. School of Medicine, Cardiff University, Cardiff, United Kingdom. Department of Haematology, The Christie NHS Foundation Trust, Manchester, United Kingdom. Department of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom. Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands. Department of Hematology, University Medical Center, University Groningen, Groningen, The Netherlands. Warwick Clinical Trials Unit, University of Warwick, Warwick, United Kingdom. MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. Department of Haematology, Oxford University Hospitals NHS Trust and Oxford Biomedical Centre, Oxford, United Kingdom. Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
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2025
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Article
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van der Maas NG, Breems D, Klerk CPW, Pabst T, Gradowska P, Thomas A, et al. A revised prognostic model for patients with acute myeloid leukemia and first relapse. Blood advances. 2025 Aug 12;9(15):3853-64. PubMed PMID: 40402082. Pubmed Central PMCID: PMC12329292 interests. Epub 2025/05/22. eng.
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