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Reply to ‘What do we mean by sensitivity when we talk about detecting minimal residual disease?’ by Steinbach and Debatin

Leukemia volume 23, pages 819–820 (2009)Cite this article

We read with interest the recent comments of Steinbach and Debatin1 concerning the definition of ‘sensitivity’ with regard to minimal residual disease (MRD). What is usually meant by ‘sensitivity’ may be described more accurately as the estimated lower limit of detection of MRD. Although Steinbach and Debatin1 write from the perspective of acute leukaemia, our experience is in the monitoring of chronic myeloid leukaemia. Recognizing important differences in the biology and treatment of acute and chronic leukaemia, there remain certain common principles of MRD monitoring that we wish to address. In particular, we emphasize that the limit of detection of MRD is dependent on (1) the performance characteristics of the analytical system and (2) the quality of the individual sample analysed.

Steinbach and Debatin1 suggest that the term ‘sensitivity’ should be reserved to describe test sensitivity (number of test positives divided by true positives), but this definition may be impractical. First, sensitivity can be calculated only if the number of true positives (true test positives+false negatives) is known. In acute leukaemia, the ‘gold standard’ indicator of the presence of MRD is relapse, and this can only be determined in retrospect. The estimation of test sensitivity using serial dilutions of cell lines with known cell numbers is possible, but this estimate of sensitivity may not be accurate when applied to patient samples. For instance, in the setting of chronic myeloid leukaemia MRD, the widely used K562 cell line has multiple copies of the BCR-ABL gene in each cell2 and expresses high levels of BCR-ABL mRNA. The choice of cell line for the determination of sensitivity will influence the result,3 and the use of cell lines to define sensitivity may overestimate the lower limit of detection (or underestimate the MRD burden) when extrapolated to patient samples.

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Authors and Affiliations

  1. Division of Haematology, Institute of Medical and Veterinary Science & School of Medicine, University of Adelaide, Adelaide, South Australia, Australia

    D M Ross, J V Melo & T P Hughes

  2. Division of Molecular Pathology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia

    S Branford

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  1. D M Ross
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  2. S Branford
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  4. T P Hughes
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Correspondence to D M Ross.

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Ross, D., Branford, S., Melo, J. et al. Reply to ‘What do we mean by sensitivity when we talk about detecting minimal residual disease?’ by Steinbach and Debatin. Leukemia 23, 819–820 (2009). https://doi.org/10.1038/leu.2008.330

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