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

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.

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Journal
Blood Advances
Published
2025-05-22
DOI
https://doi.org/10.1182/bloodadvances.2025015797
Primary Topic
Acute Myeloid Leukemia Research
Type
article
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article

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

Steven Knapper, Ian Thomas, Abin Thomas, Carlos Graux et al.
Blood Advances
Acute Myeloid Leukemia Research
article

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

Steven Knapper, Ian Thomas, Abin Thomas, Carlos Graux, Sylvie Freeman, Jurjen Versluis, Patrycja L. Gradowska, Gerwin Huls, N Maas, Nigel H. Russell, Thomas Pabst, Bob Löwenberg, Mike Dennis, Otto Visser, Jurgen H. E. Kuball, Dimitri A. Breems, Jan J. Cornelissen, Clara Klerk, Bart J. Biemond, Peter J.M. Valk, Paresh Vyas, Charles Craddock, Catharina Van Elssen, H. Berna Beverloo, Johan A. Maertens, Gert Jan Ossenkoppele, Marie-Christiane Madeleine Vekemans
article en

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.

Blood AdvancesVol. 9(15)
University Hospitals Birmingham NHS Foundation Trust (GB), Cliniques Universitaires Saint-Luc (BE), University Medical Center Groningen (NL), Guy's and St Thomas' NHS Foundation Trust (GB), Maastricht University Medical Centre (NL), Universitair Ziekenhuis Leuven (BE), University Hospital of Bern (CH), Erasmus MC (NL), University Medical Center Utrecht (NL), Maastricht University (NL), University of Warwick (GB), University of Oxford (GB), CHU Dinant Godinne UCL Namur (BE), MRC Weatherall Institute of Molecular Medicine (GB), The Christie NHS Foundation Trust (GB), Refaja Ziekenhuis (NL), Hovon (NL), Isala (NL), Oxford University Hospitals NHS Trust (GB), Swiss Group For Clinical Cancer Research (CH), GGD Amsterdam (NL), Erasmus MC Cancer Institute (NL), Ziekenhuisnetwerk Antwerpen Stuivenberg (BE), Amsterdam University Medical Centers (NL), Maastro Clinic (NL), NIHR Birmingham Biomedical Research Centre (GB), Cardiff University (GB), University of Birmingham (GB), University of Amsterdam (NL), Erasmus University Rotterdam (NL), UCLouvain (BE)
Erasmus Medisch Centrum
Openalex Percentile: Top 86%
Acute Myeloid Leukemia Research
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