Research Article

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

  1. Ester Mejstříková MD, PhD1,2,
  2. Eva Froňková MD, PhD1,2,
  3. Tomáš Kalina MD, PhD1,2,
  4. Marek Omelka PhD3,
  5. Drago Batinić MD, PhD4,
  6. Klara Dubravčić MSc4,
  7. Klára Pospíšilová1,2,
  8. Martina Vášková PhD1,2,
  9. Drorit Luria PhD5,
  10. Suk Hang Cheng BSc, PhD6,
  11. Margaret Ng MD, PhD6,
  12. Yonna Leung BSc, MSc6,
  13. Janos Kappelmayer MD, PhD7,
  14. Flora Kiss MD, PhD7,
  15. Shai Izraeli MD8,
  16. Batia Stark MD5,
  17. Martin Schrappe MD, PhD9,
  18. Jan Trka MD, PhD1,2,
  19. Jan Starý MD, PhD2,
  20. Ondřej Hrušák MD, PhD1,2,*

Article first published online: 16 SEP 2009

DOI: 10.1002/pbc.22261

Issue

Pediatric Blood & Cancer

Pediatric Blood & Cancer

Volume 54, Issue 1, pages 62–70, January 2010

Additional Information

How to Cite

Mejstříková, E., Froňková, E., Kalina, T., Omelka, M., Batinić, D., Dubravčić, K., Pospíšilová, K., Vášková, M., Luria, D., Cheng, S. H., Ng, M., Leung, Y., Kappelmayer, J., Kiss, F., Izraeli, S., Stark, B., Schrappe, M., Trka, J., Starý, J. and Hrušák, O. (2010), Detection of residual B precursor lymphoblastic leukemia by uniform gating flow cytometry. Pediatric Blood & Cancer, 54: 62–70. doi: 10.1002/pbc.22261

Author Information

  1. 1

    CLIP-Childhood Leukemia Investigation Prague, Prague, Czech Republic

  2. 2

    Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, University Hospital Motol, Prague, Czech Republic

  3. 3

    Faculty of Mathematics and Physics, Jaroslav Hájek Center for Theoretical and Applied Statistics, Charles University, Prague, Czech Republic

  4. 4

    Clinical Institute of Laboratory Diagnosis, University Clinical Hospital Centre, Zagreb, Croatia

  5. 5

    Department of Pediatric Hematology/Oncology, Schneider Children's Medical Centre of Israel, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tiqva, Israel

  6. 6

    Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, New Territories, Hong Kong

  7. 7

    Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Sciences Centre, University of Debrecen, Debrecen, Hungary

  8. 8

    Pediatric Hematology and Oncology, Scheba Medical Center, Tel Hashomer, Israel

  9. 9

    Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany

*Department of Pediatric Hematology and Oncology, 2nd Medical School and University Hospital Motol, V Úvalu 84, Prague, Czech Republic.

Publication History

  1. Issue published online: 9 NOV 2009
  2. Article first published online: 16 SEP 2009
  3. Manuscript Accepted: 29 JUL 2009
  4. Manuscript Received: 31 OCT 2008

Funded by

  • Czech Governmental and University agencies. Grant Numbers: VZMSMT MSM0021620813, IGA MZ NS1000-4, NR/9531-3/2007, GAUK 53907/2007, MZ 00064203
  • Croatian Ministry of Science, Education and Sports. Grant Number: 214-1081347-0355
  • Israeli Cancer Association

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Keywords:

  • acute lymphoblastic leukemia;
  • flow cytometry;
  • minimal residual disease;
  • non-malignant background

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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