Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1IS and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.

2nd Medical Department University Hospital Schleswig Holstein Campus Kiel Germany

3 Medizinische Klinik Universitätsmedizin Mannheim Mannheim Germany

Abteilung Hämatologie Onkologie Klinik für Innere Medizin 2 Universitätsklinikum Jena Jena Germany

Amsterdam University Medical Center Amsterdam The Netherlands

Cancer Molecular Diagnostics St James's Hospital Dublin Ireland

Centro de Investigación Biomédica en Red de Cáncer Instituto Carlos 3 28029 Madrid Spain

CHU Lille Laboratoire d'hématologie F 59000 Lille France

Clinical Genetics Karolinska University Hospital Stockholm Sweden

Department of Clinical and Experimental Medicine Center of Experimental Oncology and Hematology University of Catania Catania Italy

Department of Emergency and Organ Transplantation Hematology and Stem Cell Transplantation Unit University of Bari Aldo Moro Bari Italy

Department of Genetics and Research Centre Portuguese Oncology Institute of Porto Porto Portugal

Department of Genomics Turku University Hospital Laboratories Turku Finland

Department of Haematology University Medical Centre Ljubljana Ljubljana Slovenia

Department of Immunology Genetics and Pathology Uppsala University Uppsala Sweden

Department of Internal Medicine Hematology and Oncology University Hospital Brno Brno Czech Republic

Department of Medical Genetics National Cancer Institute Bratislava Slovakia

Department of Medical Oncology and Hematology University Hospital Zurich University of Zurich Zurich Switzerland

Department of Molecular Hemato Oncology LHUB ULB Brussels Belgium

Department of Molecular Medicine and Medical Biotechnology University 'Federico II' and CEINGE Advanced Biotechnologies Naples Italy

Department of Pathology Zealand University Hospital Roskilde Denmark

Faculty of Medicine Masaryk University Brno Czech Republic

Faculty of Medicine University of Southampton Southampton UK

Faculty of Pharmacy University of Ljubljana Ljubljana Slovenia

Fundeni Clinical Institute Hematology Department Bucharest Romania

Haematological Malignancy Diagnostic Service Leeds Teaching Hospitals Leeds UK

Haematology Research Laboratory National and Kapodistrian University of Athens School of Medicine Athens Greece

Hematological Malignancies Clinical Research Unit CNIO 28029 Madrid Spain

Hematology Department Faculty of Medicine University of Medicine and Pharmacy Carol Davila Bucharest Romania

Hematology Department Hospital Regional Universitario de Málaga IBIMA Málaga Spain

Hematology Department Hospital Universitario 12 de Octubre Instituto de Investigación Sanitaria Imas12 28041 Madrid Spain

Hematology Department Hospital Universitario de Gran Canaria Doctor Negrín Las Palmas de Gran Canaria Las Palmas Spain

HemoDiagnostic Laboratory Department of Hematology Aarhus University Hospital Aarhus Denmark

Hospices Civils de Lyon Hôpital Lyon Sud Service d'Hématologie Biologique Pierre Bénite France

Institute for Hematology and Oncology Mannheim Germany

Institute of Hematology and Blood Transfusion Prague Czech Republic

IRCSS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Bologna Italy

Labdia Labordiagnostik St Anna Children´s Cancer Research Institute Vienna Austria

Laboratório de Hemato Oncologia LHO Instituto Português de Oncologia Francisco Gentil Lisbon Portugal

Laboratory of Chemical and Clinical Analysis Area 3 A O U San Luigi Gonzaga Orbassano Turin Italy

Laboratory of Hematology University Hospital Saint Louis Université de Paris Paris France

Laboratory of Medical Genetics National Specialized Hospital for Active Treatment of Hematological Diseases Sofia Bulgaria

Laboratory of Molecular Genetics Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases Budapest Hungary

Medical University of Vienna Department of Laboratory Medicine Vienna Austria

MLL Munich Leukemia Laboratory Munich Germany

Molecular Diagnostics Laboratory Hematology Department and HCT Unit George Papanicolaou General Hospital Thessaloniki Greece

Molecular Hemapathology Oslo University Hospital Oslo Norway

Pathology Department Hospital Clinic Institut d' Investigacions Biomèdiques August Pi i Sunyer CIBERONC Barcelona Spain

Pathology Department University Clinical Center Tuzla Policlinic for Laboratory Diagnostics Tuzla Bosnia and Herzegovina

Poznan University of Medical Sciences Department of Hematology and Bone Marrow Transplantation Poznan Poland

Ritus Biotec Laboratory Codlea Brasov Romania

Section of Molecular Diagnostics Clinical Genetics Region Skåne Lund Sweden

SIHMDS Hosted by Imperial College Healthcare NHS Trust at Hammersmith Hospital London UK

The University Hospital in Krakow Krakow Poland

Transilvania University Brasov Romania

University Hospital Bern Bern Switzerland

University Hospital Center Zagreb Zagreb Croatia

University Hospital of Bordeaux Laboratory of Hematology Haut Lévêque Hospital Pessac France

University of Bern Bern Switzerland

University of Leipzig Medical Center Department for Hematology Cellular Therapies and Hemostaseology Leipzig Germany

Vilnius University Hospital Santaros Klinikos Vilnius Lithuania

Wessex Regional Genetics Laboratory Salisbury NHS Foundation Trust Salisbury UK

West Midlands Regional Genetics Laboratory Birmingham Women's and Children's NHS Foundation Trust Birmingham UK

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