Improved multistate survival in younger AML patients over time
16 affiliations
- 1Department of Hematology Erasmus University Medical Center Cancer Institute Rotterdam The Netherlands
- 2Department of Hematology, Cancer Center Amsterdam Amsterdam University Medical Centers, Vrije Universiteit University Medical Center Amsterdam The Netherlands
- 3Department of Hematology University Medical Center Groningen (UMCG) Groningen The Netherlands
- 4Department of Medical Oncology Inselspital, Bern University Hospital Bern Switzerland
- 5Department of Hematology University Medical Center Utrecht Utrecht The Netherlands
- 6Department of Hematology Isala Hospital Zwolle The Netherlands
- 7Department of Hematology University Hospitals Leuven Leuven Belgium
- 8Ziekenhuis aan de Stroom Antwerp Belgium
- 9Department of Medical Oncology and Hematology University Hospital Zurich and University of Zurich Zurich Switzerland
- 10Department of Hematology Amsterdam University Medical Center, University of Amsterdam Amsterdam The Netherlands
- 11Hematology Division University Hospital Basel Switzerland
- 12Haukeland University Hospital Bergen Norway
- 13Department of Medical Sciences Uppsala University Hospital Uppsala Sweden
- 14Department of Medicine Huddinge, Karolinska Institute Stockholm Sweden
- 15Department of Hematology HOVON Foundation Rotterdam The Netherlands
- 16Medical Statistics, Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands
Abstract
Over the last three decades, HOVON‐SAKK has performed six randomized controlled trials (RCTs) in newly diagnosed younger adults with acute myeloid leukemia (AML). While overall survival (OS) improved over time, no OS benefit was apparent in individual RCTs. We investigated whether complete remission (CR) rates, postremission treatment (PRT), and/or a reduction of early mortality might have accounted for improved OS. Two multistate models, from the start of induction treatment until the date of death or last contact, were developed. These models included (1) CR ≤ 2 cycles and (2) CR followed by type of PRT as intermediate states and overall mortality as an end state. Patients were categorized by decade of diagnosis. Transition probabilities were adjusted for age and European LeukemiaNet (ELN) 2017 risk classification. Multistate survival (MS) was defined by the probability of obtaining CR with the intention or actual receipt of PRT and surviving thereafter. A total of 924, 1896, and 2253 patients were enrolled between 1987‐1996, 1997‐2006, and 2007‐2017, respectively. OS at 5 years increased from 33 ± 2% to 47 ± 1% in the most recent cohort. CR rates increased from 77.5% to 83.9%. Sixty‐day mortality decreased from 9.9% to 7.8%. The proportion of alloHSCT as PRT increased from 16.6% to 48.3%. MS at 5 years increased from 28.8% to 47.4% and from 11.3% to 26.1% for ELN17 intermediate and adverse risk patients, which was largely due to improved OS in CR patients proceeding to alloHSCT. Increased CR rates and an increased application of alloHSCT mainly accounted for improved MS and OS. MS, as a novel endpoint, effectively captures favorable treatment outcome, while allowing quantification of the survival gain of pivotal, subsequent intermediate states.
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BibTeX
@article{hermans2026improved,
title = {{Improved multistate survival in younger AML patients over time}},
author = {Sjoerd J. F. Hermans and Jurjen Versluis and Gert J. Ossenkoppele and Edo Vellenga and Thomas Pabst and Leo F. Verdonck and Johan Maertens and Dimitri Breems and Markus G. Manz and Bart Biemond and Jürgen Kuball and Marinus van Marwijk Kooy and Mojca Jongen‐Lavrencic and Peter C. Huijgens and Jakob Passweg and Bjørn T. Gjertsen and Soren Lehmann and Patrycja Gradowska and Berna Beverloo and Peter Valk and Gerwin Huls and Liesbeth C. de Wreede and Bob Löwenberg and Jan J. Cornelissen},
journal = {HemaSphere},
year = {2026},
month = nov,
doi = {10.1002/hem3.70503},
url = {https://europepmc.org/article/PMC/PMC13730054},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Improved multistate survival in younger AML patients over time
AU - Sjoerd J. F. Hermans
AU - Jurjen Versluis
AU - Gert J. Ossenkoppele
AU - Edo Vellenga
AU - Thomas Pabst
AU - Leo F. Verdonck
AU - Johan Maertens
AU - Dimitri Breems
AU - Markus G. Manz
AU - Bart Biemond
AU - Jürgen Kuball
AU - Marinus van Marwijk Kooy
AU - Mojca Jongen‐Lavrencic
AU - Peter C. Huijgens
AU - Jakob Passweg
AU - Bjørn T. Gjertsen
AU - Soren Lehmann
AU - Patrycja Gradowska
AU - Berna Beverloo
AU - Peter Valk
AU - Gerwin Huls
AU - Liesbeth C. de Wreede
AU - Bob Löwenberg
AU - Jan J. Cornelissen
PY - 2026
DA - 2026/11/01
JO - HemaSphere
DO - 10.1002/hem3.70503
UR - https://europepmc.org/article/PMC/PMC13730054
AB - Over the last three decades, HOVON‐SAKK has performed six randomized controlled trials (RCTs) in newly diagnosed younger adults with acute myeloid leukemia (AML). While overall survival (OS) improved over time, no OS benefit was apparent in individual RCTs. We investigated whether complete remission (CR) rates, postremission treatment (PRT), and/or a reduction of early mortality might have accounted for improved OS. Two multistate models, from the start of induction treatment until the date of death or last contact, were developed. These models included (1) CR ≤ 2 cycles and (2) CR followed by type of PRT as intermediate states and overall mortality as an end state. Patients were categorized by decade of diagnosis. Transition probabilities were adjusted for age and European LeukemiaNet (ELN) 2017 risk classification. Multistate survival (MS) was defined by the probability of obtaining CR with the intention or actual receipt of PRT and surviving thereafter. A total of 924, 1896, and 2253 patients were enrolled between 1987‐1996, 1997‐2006, and 2007‐2017, respectively. OS at 5 years increased from 33 ± 2% to 47 ± 1% in the most recent cohort. CR rates increased from 77.5% to 83.9%. Sixty‐day mortality decreased from 9.9% to 7.8%. The proportion of alloHSCT as PRT increased from 16.6% to 48.3%. MS at 5 years increased from 28.8% to 47.4% and from 11.3% to 26.1% for ELN17 intermediate and adverse risk patients, which was largely due to improved OS in CR patients proceeding to alloHSCT. Increased CR rates and an increased application of alloHSCT mainly accounted for improved MS and OS. MS, as a novel endpoint, effectively captures favorable treatment outcome, while allowing quantification of the survival gain of pivotal, subsequent intermediate states.
SN - 2572-9241
ER -