Applicability and reproducibility of acute myeloid leukaemia stem cell assessment in a multi-centre setting

Research output: Contribution to journalArticle

Authors

  • Alexander N Snel
  • Angèle Kelder
  • Willemijn J Scholten
  • Naeem Khan
  • Marlen Metzner
  • Maria Irno-Consalvo
  • Mayumi Sugita
  • Anja de Jong
  • Sjoerd Oude Alink
  • Harrie Eidhof
  • Miriam Wilhelm
  • Michaela Feuring-Buske
  • Jennichjen Slomp
  • Vincent H J van der Velden
  • Edwin Sonneveld
  • Monica Guzman
  • Gail J Roboz
  • Francesco Buccisano
  • Paresh Vyas
  • Costa Bachas
  • Gert J Ossenkoppele
  • Gerrit J Schuurhuis
  • Jacqueline Cloos

External organisations

  • Universitatsklinikum, Hematology Department, Freiburg, Germany.
  • University of Oxford and Oxford University Hospitals National Health Service Trust
  • University of Rome Tor Vergata
  • Weill Cornell Medical College
  • Dutch Childhood Oncology Group
  • Department of Immunology, Erasmus Medical Center, University Medical Center, Rotterdam, the Netherlands.
  • Department of Clinical Chemistry, University Hospitals Birmingham, Birmingham
  • University Hospital of Ulm

Abstract

Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia-propagating population and are thought to be the cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements are warranted to facilitate accurate risk stratification. Previously, we published the composition of a one-tube flow cytometric assay, characterised by the presence of 13 important membrane markers for LSC detection. Here we present the validation experiments of the assay in several large AML research centres, both in Europe and the United States. Variability within instruments and sample processing showed high correlations between different instruments (Rpearson > 0·91, P < 0·001). Multi-centre testing introduced variation in reported LSC percentages but was found to be below the clinical relevant threshold. Clear gating protocols resulted in all laboratories being able to perform LSC assessment of the validation set. Participating centres were nearly unanimously able to distinguish LSChigh (>0·03% LSC) from LSClow (<0·03% LSC) despite inter-laboratory variation in reported LSC percentages. This study proves that the LSC assay is highly reproducible. These results together with the high prognostic impact of LSC load at diagnosis in AML patients render the one-tube LSC assessment a good marker for future risk classification.

Bibliographic note

© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Details

Original languageEnglish
JournalBritish Journal of Haematology
Early online date2 Apr 2020
Publication statusE-pub ahead of print - 2 Apr 2020