PURPOSE: Half the patients with acute myeloid leukemia (AML) who achieve complete remission (CR), ultimately relapse. Residual treatment-surviving leukemia is considered responsible for the outgrowth of AML. In many retrospective studies, detection of minimal residual disease (MRD) has been shown to enable identification of these poor-outcome patients by showing its independent prognostic impact. Most studies focus on molecular markers or analyze data in retrospect. This study establishes the value of immunophenotypically assessed MRD in the context of a multicenter clinical trial in adult AML with sample collection and analysis performed in a few specialized centers. PATIENTS AND METHODS: In adults (younger than age 60 years) with AML enrolled onto the Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research Acute Myeloid Leukemia 42A study, MRD was evaluated in bone marrow samples in CR (164 after induction cycle 1, 183 after cycle 2, 124 after consolidation therapy). RESULTS: After all courses of therapy, low MRD values distinguished patients with relatively favorable outcome from those with high relapse rate and adverse relapse-free and overall survival. In the whole patient group and in the subgroup with intermediate-risk cytogenetics, MRD was an independent prognostic factor. Multivariate analysis after cycle 2, when decisions about consolidation treatment have to be made, confirmed that high MRD values (> 0.1% of WBC) were associated with a higher risk of relapse after adjustment for consolidation treatment time-dependent covariate risk score and early or later CR. CONCLUSION: In future treatment studies, risk stratification should be based not only on risk estimation assessed at diagnosis but also on MRD as a therapy-dependent prognostic factor.
RCT Entities:
PURPOSE: Half the patients with acute myeloid leukemia (AML) who achieve complete remission (CR), ultimately relapse. Residual treatment-surviving leukemia is considered responsible for the outgrowth of AML. In many retrospective studies, detection of minimal residual disease (MRD) has been shown to enable identification of these poor-outcome patients by showing its independent prognostic impact. Most studies focus on molecular markers or analyze data in retrospect. This study establishes the value of immunophenotypically assessed MRD in the context of a multicenter clinical trial in adult AML with sample collection and analysis performed in a few specialized centers. PATIENTS AND METHODS: In adults (younger than age 60 years) with AML enrolled onto the Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research Acute Myeloid Leukemia 42A study, MRD was evaluated in bone marrow samples in CR (164 after induction cycle 1, 183 after cycle 2, 124 after consolidation therapy). RESULTS: After all courses of therapy, low MRD values distinguished patients with relatively favorable outcome from those with high relapse rate and adverse relapse-free and overall survival. In the whole patient group and in the subgroup with intermediate-risk cytogenetics, MRD was an independent prognostic factor. Multivariate analysis after cycle 2, when decisions about consolidation treatment have to be made, confirmed that high MRD values (> 0.1% of WBC) were associated with a higher risk of relapse after adjustment for consolidation treatment time-dependent covariate risk score and early or later CR. CONCLUSION: In future treatment studies, risk stratification should be based not only on risk estimation assessed at diagnosis but also on MRD as a therapy-dependent prognostic factor.
Authors: Bob Löwenberg; Thomas Pabst; Johan Maertens; Patrycja Gradowska; Bart J Biemond; Olivier Spertini; Edo Vellenga; Laimonas Griskevicius; Lidwine W Tick; Mojca Jongen-Lavrencic; Marinus van Marwijk Kooy; Marie-Christiane Vekemans; Walter J F M van der Velden; Berna Beverloo; Lucienne Michaux; Carlos Graux; Dries Deeren; Okke de Weerdt; Joost W J van Esser; Mario Bargetzi; Saskia K Klein; Alain Gadisseur; Peter E Westerweel; Hendrik Veelken; Michael Gregor; Tobias Silzle; Daniëlle van Lammeren-Venema; Ine Moors; Dimitri A Breems; Mels Hoogendoorn; Marie-Cecile J C Legdeur; Thomas Fischer; Juergen Kuball; Jan Cornelissen; Kimmo Porkka; Gunnar Juliusson; Peter Meyer; Martin Höglund; Bjorn T Gjertsen; Jeroen J W M Janssen; Gerwin Huls; Jakob Passweg; Jacqueline Cloos; Peter J M Valk; Catharina H M J van Elssen; Markus G Manz; Yngvar Floisand; Gert J Ossenkoppele Journal: Blood Adv Date: 2021-02-23
Authors: Burak Kalin; Yvette van Norden; Michel van Gelder; Dimitri Breems; Johan Maertens; Mojca Jongen-Lavrencic; Annoek E C Broers; Eric Braakman; Tim Grob; Wendelien Zeijlemaker; Gert J Ossenkoppele; Ellen Meijer; Jan J Cornelissen Journal: Blood Adv Date: 2020-09-22