Standardization of molecular monitoring of CML: results and recommendations from the European treatment and outcome study.

Helen E White, Matthew Salmon, Francesco Albano, Christina Søs Auður Andersen, Stefan Balabanov, Gueorgui Balatzenko, Gisela Barbany, Jean-Michel Cayuela, Nuno Cerveira, Pascale Cochaux, Dolors Colomer, Daniel Coriu, Joana Diamond, Christian Dietz, Stéphanie Dulucq, Marie Engvall, Georg N Franke, Egle Gineikiene-Valentine, Michal Gniot, María Teresa Gómez-Casares, Enrico Gottardi, Chloe Hayden, Sandrine Hayette, Andreas Hedblom, Anca Ilea, Barbara Izzo, Antonio Jiménez-Velasco, Tomas Jurcek, Veli Kairisto, Stephen E Langabeer, Thomas Lion, Nora Meggyesi, Semir Mešanović, Luboslav Mihok, Gerlinde Mitterbauer-Hohendanner, Sylvia Moeckel, Nicole Naumann, Olivier Nibourel, Elisabeth Oppliger Leibundgut, Panayiotis Panayiotidis, Helena Podgornik, Christiane Pott, Inmaculada Rapado, Susan J Rose, Vivien Schäfer, Tasoula Touloumenidou, Christopher Veigaard, Bianca Venniker-Punt, Claudia Venturi, Paolo Vigneri, Ingvild Vorkinn, Elizabeth Wilkinson, Renata Zadro, Magdalena Zawada, Hana Zizkova, Martin C Müller, Susanne Saussele, Thomas Ernst, Katerina Machova Polakova, Andreas Hochhaus, Nicholas C P Cross

Journal: Leukemia 2022;36(7):1834-1842

PMID: 35614319

Abstract

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 MR in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1 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.

© 2022. The Author(s).

Address: Faculty of Medicine, University of Southampton, Southampton, UK.; Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, UK.; Department of Emergency and Organ Transplantation (D.E.T.O.)-Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy.; Department of Pathology, Zealand University Hospital, Roskilde, Denmark.; Department of Medical Oncology and Hematology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.; Laboratory of Medical Genetics National Specialized Hospital for Active Treatment of Hematological Diseases, Sofia, Bulgaria.; Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.; Laboratory of Hematology, University Hospital Saint-Louis, Université de Paris, Paris, France.; Department of Genetics and Research Centre, Portuguese Oncology Institute of Porto, Porto, Portugal.; Department of Molecular Hemato-Oncology, LHUB-ULB, Brussels, Belgium.; Pathology Department, Hospital Clinic, Institut d' Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERONC, Barcelona, Spain.; Fundeni Clinical Institute, Hematology Department, Bucharest, Romania.; Hematology Department, Faculty of Medicine, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania.; Laboratório de Hemato-Oncologia-LHO Instituto Português de Oncologia Francisco Gentil, Lisbon, Portugal.; Institute for Hematology and Oncology (IHO GmbH), Mannheim, Germany.; University Hospital of Bordeaux, Laboratory of Hematology, Haut Lévêque Hospital, Pessac, France.; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.; University of Leipzig Medical Center, Department for Hematology, Cellular Therapies and Hemostaseology, Leipzig, Germany.; Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania.; Poznan University of Medical Sciences, Department of Hematology and Bone Marrow Transplantation, Poznan, Poland.; Hematology Department, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Las Palmas, Spain.; Laboratory of Chemical and Clinical Analysis "Area 3" A.O.U San Luigi Gonzaga-Orbassano, Turin, Italy.; SIHMDS Hosted by Imperial College Healthcare NHS Trust at Hammersmith Hospital, London, UK.; Hospices Civils de Lyon, Hôpital Lyon Sud, Service d'Hématologie Biologique, Pierre-Bénite, France.; Section of Molecular Diagnostics, Clinical Genetics, Region Skåne, Lund, Sweden.; Ritus Biotec Laboratory, Codlea-Brasov, Romania.; Transilvania University, Brasov, Romania.; Department of Molecular Medicine and Medical Biotechnology University 'Federico II' and CEINGE-Advanced Biotechnologies, Naples, Italy.; Hematology Department, Hospital Regional Universitario de Málaga, IBIMA, Málaga, Spain.; Department of Internal Medicine-Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.; Faculty of Medicine, Masaryk University, Brno, Czech Republic.; Department of Genomics, Turku University Hospital Laboratories, Turku, Finland.; Cancer Molecular Diagnostics, St. James's Hospital, Dublin, Ireland.; Labdia Labordiagnostik/St. Anna Children´s Cancer Research Institute (CCRI), Vienna, Austria.; Laboratory of Molecular Genetics, Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases, Budapest, Hungary.; Pathology Department, University Clinical Center Tuzla, Policlinic for Laboratory Diagnostics, Tuzla, Bosnia and Herzegovina.; Department of Medical Genetics, National Cancer Institute, Bratislava, Slovakia.; Medical University of Vienna, Department of Laboratory Medicine, Vienna, Austria.; MLL Munich Leukemia Laboratory, Munich, Germany.; III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany.; CHU Lille, Laboratoire d'hématologie, F-59000, Lille, France.; University Hospital Bern, Bern, Switzerland.; University of Bern, Bern, Switzerland.; Haematology Research Laboratory, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.; Department of Haematology, University Medical Centre Ljubljana, Ljubljana, Slovenia.; Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.; Second Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Germany.; Hematology Department, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Imas12, 28041, Madrid, Spain.; Hematological Malignancies Clinical Research Unit, CNIO, 28029, Madrid, Spain.; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, 28029, Madrid, Spain.; West Midlands Regional Genetics Laboratory, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK.; Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany.; Molecular Diagnostics Laboratory, Hematology Department and HCT Unit, George Papanicolaou General Hospital, Thessaloniki, Greece.; HemoDiagnostic Laboratory, Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.; Amsterdam University Medical Center, Amsterdam, The Netherlands.; IRCSS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", Bologna, Italy.; Department of Clinical and Experimental Medicine, Center of Experimental Oncology and Hematology, University of Catania, Catania, Italy.; Molecular Hemapathology, Oslo University Hospital, Oslo, Norway.; Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, Leeds, UK.; University Hospital Center Zagreb, Zagreb, Croatia.; The University Hospital in Krakow, Krakow, Poland.; Institute of Hematology and Blood Transfusion, Prague, Czech Republic.; Faculty of Medicine, University of Southampton, Southampton, UK. [email protected].; Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, UK. [email protected].
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