Detection of residual B precursor lymphoblastic leukemia by uniform gating flow cytometry

Authors

  • Ester Mejstříková MD, PhD,

    1. CLIP-Childhood Leukemia Investigation Prague, Prague, Czech Republic
    2. Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic
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  • Eva Froňková MD, PhD,

    1. CLIP-Childhood Leukemia Investigation Prague, Prague, Czech Republic
    2. Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic
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  • Tomáš Kalina MD, PhD,

    1. CLIP-Childhood Leukemia Investigation Prague, Prague, Czech Republic
    2. Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic
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  • Marek Omelka PhD,

    1. Faculty of Mathematics and Physics, Jaroslav Hájek Center for Theoretical and Applied Statistics, Charles University, Prague, Czech Republic
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  • Drago Batinić MD, PhD,

    1. Clinical Institute of Laboratory Diagnosis, University Clinical Hospital Centre, Zagreb, Croatia
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  • Klara Dubravčić MSc,

    1. Clinical Institute of Laboratory Diagnosis, University Clinical Hospital Centre, Zagreb, Croatia
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  • Klára Pospíšilová,

    1. CLIP-Childhood Leukemia Investigation Prague, Prague, Czech Republic
    2. Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic
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  • Martina Vášková PhD,

    1. CLIP-Childhood Leukemia Investigation Prague, Prague, Czech Republic
    2. Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic
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  • Drorit Luria PhD,

    1. Department of Pediatric Hematology/Oncology, Schneider Children's Medical Centre of Israel, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tiqva, Israel
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  • Suk Hang Cheng BSc, PhD,

    1. Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, New Territories, Hong Kong
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  • Margaret Ng MD, PhD,

    1. Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, New Territories, Hong Kong
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  • Yonna Leung BSc, MSc,

    1. Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, New Territories, Hong Kong
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  • Janos Kappelmayer MD, PhD,

    1. Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Sciences Centre, University of Debrecen, Debrecen, Hungary
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  • Flora Kiss MD, PhD,

    1. Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Sciences Centre, University of Debrecen, Debrecen, Hungary
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  • Shai Izraeli MD,

    1. Pediatric Hematology and Oncology, Scheba Medical Center, Tel Hashomer, Israel
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  • Batia Stark MD,

    1. Department of Pediatric Hematology/Oncology, Schneider Children's Medical Centre of Israel, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tiqva, Israel
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  • Martin Schrappe MD, PhD,

    1. Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany
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  • Jan Trka MD, PhD,

    1. CLIP-Childhood Leukemia Investigation Prague, Prague, Czech Republic
    2. Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic
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  • Jan Starý MD, PhD,

    1. Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic
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  • Ondřej Hrušák MD, PhD

    Corresponding author
    1. CLIP-Childhood Leukemia Investigation Prague, Prague, Czech Republic
    2. Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic
    • Department of Pediatric Hematology and Oncology, 2nd Medical School and University Hospital Motol, V Úvalu 84, Prague, Czech Republic.
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Abstract

Background

Residual disease (RD) is an important prognostic factor in acute lymphoblastic leukemia (ALL). Flow cytometry (FC)-based RD detection is easy to perform, but interpretation requires expert analysis due to individual differences among patients.

Procedure

We focused at the design of standardized and reproducible RD monitoring in ALL. RD was investigated by a uniform gating strategy, which was designed internationally and tested in one center by Ig/TCR rearrangements.

Results

For each gate, positivity cutoff value was assigned using quantification of non-leukemic background. Comparing to Ig/TCR at 0.1% level, 80 of 103 specimens were correctly diagnosed by FC. The predictive value of FC RD at day 15 was then analyzed. In B lineage ALL, day 15 FC significantly correlated with Ig/TCR results at day 33 and/or week 12 (P < 0.01). No significant correlation was found in T lineage ALL.

Conclusions

Thus, FC with preset uniform gating at day 15 predicts PCR-detectable MRD in B precursor ALL. Presented data may be used to define new polychromatic cytometric diagnostics of MRD including semiautomatic assessment. Pediatr Blood Cancer 2010; 54:62–70. © 2009 Wiley-Liss, Inc.

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