Identification of critical hemodilution by artificial intelligence in bone marrow assessed for minimal residual disease analysis in acute myeloid leukemia: The Cinderella method

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Joerg Hoffmann - , University Hospital Gießen and Marburg (Author)
  • Michael C Thrun - , University Hospital Gießen and Marburg (Author)
  • Maximilian A Röhnert - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Malte von Bonin - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Uta Oelschlägel - , Department of internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Andreas Neubauer - , University Hospital Gießen and Marburg (Author)
  • Alfred Ultsch - , University Hospital Gießen and Marburg (Author)
  • Cornelia Brendel - , University Hospital Gießen and Marburg (Author)

Abstract

Minimal residual disease (MRD) detection is a strong predictor for survival and relapse in acute myeloid leukemia (AML). MRD can be either determined by molecular assessment strategies or via multiparameter flow cytometry. The degree of bone marrow (BM) dilution with peripheral blood (PB) increases with aspiration volume causing consecutive underestimation of the residual AML blast amount. In order to prevent false-negative MRD results, we developed Cinderella, a simple automated method for one-tube simultaneous measurement of hemodilution in BM samples and MRD level. The explainable artificial intelligence (XAI) Cinderella was trained and validated with the digital raw data of a flow cytometric "8-color" AML-MRD antibody panel in 126 BM and 23 PB samples from 35 patients. Cinderella predicted PB dilution with high accordance compared to the results of the Holdrinet formula (Pearson's correlation coefficient r = 0.94, R2 = 0.89, p < 0.001). Unlike conventional neuronal networks Cinderella calculated the distributions of 12 different cell populations that were assigned to true hematopoietic counterparts as a human in the loop (HIL) approach. Besides characteristic BM cells such as myelocytes and myeloid progenitor cells the XAI identified discriminating populations, which were not specific for BM or PB (e.g., T cell/NK cell subpopulations and CD45 negative cells) and considered their frequency differences. Thus, Cinderella represents a HIL-XAI algorithm capable to calculate the degree of hemodilution in BM samples with an AML MRD immunophenotype panel. It is explicable, transparent, and paves a simple way to prevent false negative MRD reports.

Details

Original languageEnglish
Pages (from-to)304-312
Number of pages9
JournalCytometry. Part A : the journal of the International Society for Analytical Cytology
Volume103
Issue number4
Publication statusPublished - Apr 2023
Peer-reviewedYes

External IDs

Scopus 85137856959

Keywords

Sustainable Development Goals

Keywords

  • Humans, Bone Marrow, Neoplasm, Residual/diagnosis, Artificial Intelligence, Hemodilution, Leukemia, Myeloid, Acute