Automated quantification of measurable residual disease in chronic lymphocytic leukemia using an artificial intelligence-assisted workflow.

Journal: Cytometry. Part B, Clinical cytometry
PMID:

Abstract

Detection of measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) is an important prognostic marker. The most common CLL MRD method in current use is multiparameter flow cytometry, but availability is limited by the need for expert manual analysis. Automated analysis has the potential to expand access to CLL MRD testing. We evaluated the performance of an artificial intelligence (AI)-assisted multiparameter flow cytometry (MFC) workflow for CLL MRD. We randomly selected 113 CLL MRD FCS files and divided them into training and validation sets. The training set (n = 41) was gated by expert manual analysis and used to train the AI model. We then compared the validation set (n = 72) MRD results obtained by the AI-assisted analysis versus those by expert manual analysis using the Pearson correlation coefficient and Bland-Altman plot method. In the validation set, the AI-assisted analysis correctly categorized cases as MRD-negative versus MRD-positive in 96% of cases. When comparing the AI-assisted analysis versus the expert manual analysis, the Pearson r was 0.8650, mean bias was 0.2237 log units, and the 95% limit of agreement (LOA) was ±1.0282 log units. The AI-assisted analysis performed sub-optimally in atypical immunophenotype CLL and in cases lacking residual normal B cells. When excluding these outlier cases, the mean bias improved to 0.0680 log units and the 95% LOA to ±0.2926 log units. An automated AI-assisted workflow allows for the quantification of MRD in CLL with typical immunophenotype. Further work is required to improve performance in atypical immunophenotype CLL.

Authors

  • Alexandre Bazinet
    Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, Texas, United States.
  • Alan Wang
    DeepCyto LLC, West Linn, Oregon, United States.
  • Xinmei Li
    School of Computer Science and Information Security, Guilin University of Electronic Technology, Guilin 541004, China.
  • Fuli Jia
    Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States.
  • Huan Mo
    Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Wei Wang
    State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
  • Sa A Wang
    Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States.