High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study

Publication

High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study

Journal Paper/Review - Sep 23, 2013

Terwijn Monique, Graux Carlos, Bargetzi Mario, Legdeur Marie-Cecile, Kuball Jurgen, de Weerdt Okke, Chalandon Yves, Hess Urs, Verdonck Leo F, Gratama Jan W, Oussoren Yvonne J M, Scholten Willemijn J, Slomp Jennita, Snel Alexander N, Vekemans Marie-Christiane, Löwenberg Bob, Ossenkoppele Gert J, Wijermans Pierre, van Gelder Michel, van Putten Wim L J, Kelder Angèle, van der Velden Vincent H J, Brooimans Rik A, Pabst Thomas, Maertens Johan, Boeckx Nancy, de Greef Georgine E, Valk Peter J M, Preijers Frank W M B, Huijgens Peter C, Dräger Angelika M, Schanz Urs, Jongen-Lavrecic Mojca, Biemond Bart J, Passweg Jakob R, Schuurhuis Gerrit J

Citation

Terwijn M, Graux C, Bargetzi M, Legdeur M, Kuball J, de Weerdt O, Chalandon Y, Hess U, Verdonck L, Gratama J, Oussoren Y, Scholten W, Slomp J, Snel A, Vekemans M, Löwenberg B, Ossenkoppele G, Wijermans P, van Gelder M, van Putten W, Kelder A, van der Velden V, Brooimans R, Pabst T, Maertens J, Boeckx N, de Greef G, Valk P, Preijers F, Huijgens P, Dräger A, Schanz U, Jongen-Lavrecic M, Biemond B, Passweg J, Schuurhuis G. High prognostic impact of flow cytometric minimal residual disease detection in acute myeloid leukemia: data from the HOVON/SAKK AML 42A study. J Clin Oncol 2013; 31:3889-97.

Type

Journal Paper/Review (English)

Journal

J Clin Oncol 2013; 31

Publication Date

Sep 23, 2013

Issn Electronic

1527-7755

Pages

3889-97

Brief description/objective

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.