Technical Aspects of Flow Cytometry-based Measurable Residual Disease Quantification in Acute Myeloid Leukemia: Experience of the European LeukemiaNet MRD Working Party
Jesse M. Tettero,
Sylvie Freeman,
Veit Buecklein,
Adriano Venditti,
Luca Maurillo,
Wolfgang Kern,
Roland B. Walter,
Brent L. Wood,
Christophe Roumier,
Jan Philippé,
Barbara Denys,
Jeffrey L. Jorgensen,
Marie C. Bene,
Francis Lacombe,
Adriana Plesa,
Monica L. Guzman,
Agnieszka Wierzbowska,
Anna Czyz,
Lok Lam Ngai,
Adrian Schwarzer,
Costa Bachas,
Jacqueline Cloos,
Marion Subklewe,
Michaela Fuering-Buske,
Francesco Buccisano
Affiliations
Jesse M. Tettero
1 Department of Hematology, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands
Sylvie Freeman
2 Department of Clinical Immunology, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, United Kingdom
Veit Buecklein
3 Department of Medicine III, University Hospital, LMU Munich, Germany
Adriano Venditti
4 Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
Luca Maurillo
4 Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
Wolfgang Kern
5 MLL Munich Leukemia Laboratory, Munich, Germany
Roland B. Walter
6 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
Brent L. Wood
7 Department of Pathology and Laboratory Medicine, Childrens Hospital Los Angeles, California, USA
Christophe Roumier
8 Laboratory of Hematology, CHU Lille, France
Jan Philippé
9 Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
Barbara Denys
9 Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
Jeffrey L. Jorgensen
10 Department of Hematopathology, UT MD Anderson Cancer Center, Houston, Texas, USA
Marie C. Bene
11 Hematology Biology, Nantes University Hospital, Nantes, France
Francis Lacombe
12 Flow Cytometry Platform, University Hospital, Bordeaux, France
Adriana Plesa
13 Laboratory of Hematology and Flow Cytometry, CHU Lyon-Sud Hospital, Hospices Civils de Lyon, France
Monica L. Guzman
14 Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, New York, USA
Agnieszka Wierzbowska
15 Department of Hematology, Medical University of Lodz, Poland
Anna Czyz
16 Department of Hematology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland
Lok Lam Ngai
1 Department of Hematology, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands
Adrian Schwarzer
17 Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Costa Bachas
1 Department of Hematology, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands
Jacqueline Cloos
1 Department of Hematology, Amsterdam UMC, Location VUmc, Amsterdam, The Netherlands
Marion Subklewe
3 Department of Medicine III, University Hospital, LMU Munich, Germany
Michaela Fuering-Buske
18 Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany.
Francesco Buccisano
4 Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
Measurable residual disease (MRD) quantified by multiparameter flow cytometry (MFC) is a strong and independent prognostic factor in acute myeloid leukemia (AML). However, several technical factors may affect the final read-out of the assay. Experts from the MRD Working Party of the European LeukemiaNet evaluated which aspects are crucial for accurate MFC-MRD measurement. Here, we report on the agreement, obtained via a combination of a cross-sectional questionnaire, live discussions, and a Delphi poll. The recommendations consist of several key issues from bone marrow sampling to final laboratory reporting to ensure quality and reproducibility of results. Furthermore, the experiences were tested by comparing two 8-color MRD panels in multiple laboratories. The results presented here underscore the feasibility and the utility of a harmonized theoretical and practical MFC-MRD assessment and are a next step toward further harmonization.
