High Prognostic Impact of Flow Cytometric Minimal Residual Disease Detection in Acute Myeloid Leukemia: Data From the HOVON/SAKK AML 42A Study

TLDR

Acute myeloid leukemia patients who achieve complete remission often relapse due to residual leukemic cells, and retrospective studies have shown that minimal residual disease (MRD) detection provides independent prognostic information, though most focus on molecular markers. This multicenter trial aimed to determine the prognostic value of immunophenotypic MRD assessment in adults under 60 with AML by evaluating bone‑marrow MRD after induction and consolidation. MRD was measured in bone‑marrow samples from 164, 183, and 124 patients after induction cycle 1, cycle 2, and consolidation, respectively, using flow cytometry in a few specialized centers. Low MRD levels after all therapy cycles independently predicted favorable relapse‑free and overall survival, with high MRD (>0.1 % of WBC) after cycle 2 linked to increased relapse risk, underscoring MRD as a therapy‑dependent prognostic factor for risk stratification.

Abstract

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.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).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.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.