Is there a need for morphologic exam to detect relapse in aml if multi-parameter flow cytometry is employed?

Access through your institution Buy or subscribe For many years, examination of the bone marrow in acute myeloid leukemia (AML) was largely limited to morphology. The WHO criterion for the

diagnosis remains a marrow with ⩾20% blasts as assessed morphologically,1 while a diagnosis of relapse requires the presence, also based on morphology, of ⩾5% myeloblasts.2 The 5%

requirement reflects observations that normal subjects can have up to 5% blasts as identified morphologically. In contrast to the 5% sensitivity of morphologic exam, multi-parameter flow

cytometry (MFC) can currently detect one abnormal myeloblast among 1000–10 000 white cells for a sensitivity of 0.1–0.01%,3 although there is debate about the relative advantages and

disadvantages of the two principal methodologies: detection of patient-specific leukemia-associated immunophenotypes (LAIP) and use of a fixed antibody panel to distinguish normal cells from

abnormal leukemia cells, irrespective of diagnostic leukemia immunophenotype (‘different-from-normal method’, the method used here).3 In contrast to enumerating blasts, MFC can in many

cases define more than one LAIP, thus increasing MFC’s sensitivity.3 The 50–500-fold greater sensitivity of MFC suggests that if morphologic exam demonstrates ⩾5% blasts, MFC will

essentially invariably be positive except when the excess blasts identified morphologically reflect active regeneration of normal marrow; in these cases, perhaps more common in children, the

negative MFC result provides the more accurate predictor of subsequent clinical outcome.4 Under these circumstances it seems reasonable to consider dispensing with morphologic exam in cases

where MFC is negative. This is particularly true since morphology is time consuming, subjective and adds further expense; at our institution results of morphologic exam are usually reported

at least 1 day after results of MFC. Furthermore, although MFC has, fairly enough, been criticized for lack of standardization and hence reproducibility, it is not obvious that morphologic

enumeration of marrow blast percent is entirely reproducible either. Under the ELN’s recommendation for examination of 500 cells,5 disagreement on identification of only 10 cells is needed

to convert a report of 6% blasts (relapse) to 4% blasts (no relapse). A repeat marrow examination may not totally address the problem given the heterogeneity of the marrow as an organ. Even

ignoring disagreement on identification of individual cells, 95% confidence intervals for 20/500 blasts (4%) and 30/500 (6%) blasts overlap: 2–6% and 4–8%. Obviously MFC evaluates several

orders of magnitude more cells than morphology with consequently smaller confidence intervals. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access

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subscriptions * Read our FAQs * Contact customer support REFERENCES * Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM _et al_. The 2016 revision to the World Health

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CONTRIBUTIONS YZ, BLW and EE designed the research, performed the analyses and wrote the paper. YZ, CS and KG provided data for the analyses. RBW, PSB, M-EP, MB, PH, JA and FRA reviewed the

letter and made suggestions. All authors approved the final submission. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Hematopathology, Department of Laboratory Medicine,

University of Washington, Seattle, WA, USA Y Zhou & B L Wood * Division of Hematology, Department of Medicine, University of Washington, Seattle, WA, USA R B Walter, P S Becker, M-E

Percival, K Gardner, P Hendrie, J Abkowitz & E Estey * Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA R B Walter, P S Becker, M-E Percival, M Bar, C

Shaw, F R Appelbaum & E Estey * Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA M Bar & F R Appelbaum Authors * Y Zhou View author

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Google Scholar CORRESPONDING AUTHOR Correspondence to E Estey. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Zhou, Y., Wood, B., Walter, R. _et al._ Is there a need for morphologic exam to detect relapse in AML if multi-parameter flow cytometry is

employed?. _Leukemia_ 31, 2536–2537 (2017). https://doi.org/10.1038/leu.2017.263 Download citation * Published: 18 August 2017 * Issue Date: November 2017 * DOI:

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