Normal or reactive minor cell populations in bone marrow and peripheral blood mimic minimal residual leukemia by flow cytometry

Cytometry B Clin Cytom. 2021 Sep;100(5):590-601. doi: 10.1002/cyto.b.21968. Epub 2020 Nov 16.

Abstract

Background: Measurable residual disease (MRD) is a strong independent poor prognostic factor for acute leukemia. Multiparameter flow cytometry (FCM) is a commonly used MRD detection method. However, FCM MRD detection is not well standardized, and the interpretation is subjective. There are normal/reactive minor cell populations in bone marrow (BM) and peripheral blood (PB), which could be confused with MRD.

Methods: The FCM data of 231 BM and 44 PB pediatric samples performed in a recent 15-month period were retrospectively reviewed. These samples were from 56 B-lymphoblastic leukemia (B-ALL) patients, 11 T-lymphoblastic leukemia (T-ALL) patients, 28 acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients, 44 cytopenia/leukocytosis patients, and five patients with mycosis fungoides.

Results: There were over 10 normal or reactive minor cell populations identified with certain phenotypes mimicking MRD of acute leukemia. These mimickers included CD19+ NK cells, CD22+ basophils, CD22+ dendritic cells (DCs), and plasma cells for B-ALL MRD; CD4/8 double-negative T cells, CD4/8 double-positive T cells, cytoplasmic CD3+ NK cells, CD2- T cells, CD7- T cells, CD5- gamma delta T cells, CD56+ NKT cells for T-ALL MRD; CD33+ NK cells, CD117+ NK cells, basophils, plasmacytoid DCs, non-classical monocytes, CD56+ and/or CD61+ monocytes for AML MRD.

Conclusions: These data confirm the presence of a variety of normal/reactive minor cell populations that could mimic MRD of acute leukemia by FCM. Recognizing these MRD mimickers is important for correct FCM MRD interpretation.

Keywords: MRD mimickers; acute leukemia; flow cytometry; minimal residual disease.

MeSH terms

  • Adolescent
  • Adult
  • Bone Marrow / pathology*
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry*
  • Humans
  • Infant
  • Infant, Newborn
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Peripheral Blood Stem Cells / pathology*
  • Young Adult