A revised prognostic model for patients with acute myeloid leukemia and first relapse
van der Maas, Niek G Breems, Dimitri Klerk, Clara P W Pabst, Thomas Gradowska, Patrycja Thomas, Abin Biemond, Bart J Kuball, Jurgen Van Elssen, Catharina H M J Visser, Otto
van der Maas, Niek G
Breems, Dimitri
Klerk, Clara P W
Pabst, Thomas
Gradowska, Patrycja
Thomas, Abin
Biemond, Bart J
Kuball, Jurgen
Van Elssen, Catharina H M J
Visser, Otto
Affiliation
Erasmus University Medical Center Cancer Institute; Cadix Hospital; Dijklander Hospital; University Hospital Inselspital; Swiss Group for Clinical Cancer Research; HOVON Foundation; Cardiff University; Amsterdam University Medical Center; University of Amsterdam; University Medical Centre Utrecht; Utrecht University; Maastricht University Medical Center; Isala Hospital; Cliniques Universitaires Saint-Luc; Université Catholique de Louvain; University Hospital Center Namur; University Hospital Gasthuisberg; Christie NHS Foundation Trust; University of Birmingham; University Groningen; University of Warwick; University of Oxford; Oxford University Hospitals NHS Trust; Guy's and St Thomas' NHS Foundation Trust
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Publication date
2025-05-22
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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.
Citation
van der Maas NG, Breems D, Klerk CPW, Pabst T, Gradowska P, Thomas A, Biemond BJ, Kuball J, Van Elssen CHMJ, Visser O, Vekemans MC, Graux C, Maertens J, Knapper S, Dennis M, Freeman S, Thomas I, Beverloo HB, Huls G, Craddock C, Valk PJM, Vyas P, Russell N, Ossenkoppele G, Löwenberg B, Cornelissen JJ, Versluis J. A revised prognostic model for patients with acute myeloid leukemia and first relapse. Blood Adv. 2025 Aug 12;9(15):3853-3864. doi: 10.1182/bloodadvances.2025015797.
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Article