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Applicability of a reproducible flow cytometry scoring system in the diagnosis of refractory cytopenia of childhood

Leukemia volume 27, pages 1923–1925 (2013)Cite this article

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Myelodysplastic syndrome (MDS) in childhood is rare and has an estimated incidence per year of about 0.8–1.8 per million children aged 0 to 14 years.1, 2, 3 The most common subtype of childhood MDS, accounting for about half of all cases, is refractory cytopenia of childhood (RCC), defined as myelodysplasia without an increased blast count.4, 5 Karyotype is normal in the majority of patients with RCC, and, in contrast to adults with MDS-refractory anemia, about 80% of children have a hypocellular bone marrow (BM).6 Although morphologic criteria for diagnosing RCC are strictly defined,5 differentiating RCC from the immune-mediated BM failure syndrome aplastic anemia can be challenging. Similarly, difficulties can be encountered in differentiating, based on morphologic criteria, non-clonal cytopenias from low-grade MDS in adults, especially in cases without cytogenetic aberrations or specific morphologic abnormalities such as ring sideroblasts. Flow cytometric immunophenotyping has been suggested as valuable addition to morphology in the diagnosis of MDS.7 Recently, Ogata and others described a simple, reproducible flow cytometric scoring system as diagnostic tool in adult low-grade MDS with a sensitivity of 70% and a specificity of 93%.8, 9 The diagnostic utility of this scoring system in RCC is unknown. Here we describe its applicability in childhood MDS, with emphasis on RCC, using pediatric advanced MDS patients, low-grade adult MDS patients, healthy individuals and cytopenic non-MDS patients as controls.

BM samples obtained from 82 primary RCC patients (median age: 10.5 years, range: 1.3–17.9), not previously treated with immunosuppressive therapy, were available for analysis by flow cytometry. Patients were diagnosed from June 2005–December 2011 and enrolled in the prospective, multi-center studies EWOG-MDS 2006 and EWOG-MDS RC06 (ClinicalTrial.gov: NCT00662090 and NCT00499070). BM was hypocellular in 66 patients (81%), and normo- or hypercellular in 16 of 82 patients (20%). Cytogenetic analysis was normal in 62 patients (76%), monosomy 7 was present in 5 patients (6%), and other aberrations in 5 patients (6%); in 10 of 82 patients (12%) no result was obtained due to insufficient metaphases. Institutional review boards of participating institutions approved the studies and parents or legal guardians of patients provided written informed consent for study participation. RCC was diagnosed according to WHO criteria5 and confirmed by central review of BM morphology and histology.10

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Acknowledgements

AMA was supported by the KiKa Foundation, Amstelveen, the Netherlands.

Author contributions

AMA, MHE, VHJV conceived the research question; AMA, JGM, AJ, VHJV, MHE analyzed the data; MHE, VH, MB, MD, HH, FL, BM, MSL, JS, MZ, AAL, JJMD, CMN, VHJV contributed samples or analysis tools, AMA, VHJV, MHE wrote the paper, and all authors approved the final version of the paper.

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Authors and Affiliations

  1. Department of Immunology, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands

    A M Aalbers, J G te Marvelde, M van der Burg, J J M van Dongen & V H J van der Velden

  2. Department of Pediatric Oncology/Hematology, Sophia Children’s Hospital - Erasmus University Medical Center, Rotterdam, The Netherlands

    A M Aalbers, M M van den Heuvel-Eibrink & C M Zwaan

  3. Dutch Childhood Oncology Group, The Hague, The Netherlands

    V de Haas & A X de Jong

  4. Department of Pediatrics, St Anna Children’s Hospital and Children’s Cancer Research Institute, Medical University of Vienna, Vienna, Austria

    M Dworzak

  5. Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark

    H Hasle

  6. Department of Pediatric Hematology-Oncology, IRCCS Ospedale Bambino Gesù, Rome, University of Pavia, Rome, Italy

    F Locatelli

  7. Department of Pediatric Hematology/Oncology, Ghent University Hospital, Ghent, Belgium

    B De Moerloose

  8. Department of Hematology, University Children’s Hospital, Zürich, Switzerland

    M Schmugge

  9. Department of Pediatric Hematology/Oncology, Charles University and University Hospital Motol, Prague, Czech Republic

    J Stary

  10. Department of Pediatric Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    M Zecca

  11. Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands

    A A van de Loosdrecht

  12. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University of Freiburg, Freiburg, Germany

    C M Niemeyer

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  1. A M Aalbers
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  2. M M van den Heuvel-Eibrink
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  15. A A van de Loosdrecht
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  16. J J M van Dongen
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  17. C M Niemeyer
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  18. V H J van der Velden
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Corresponding author

Correspondence to V H J van der Velden.

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Aalbers, A., van den Heuvel-Eibrink, M., de Haas, V. et al. Applicability of a reproducible flow cytometry scoring system in the diagnosis of refractory cytopenia of childhood. Leukemia 27, 1923–1925 (2013). https://doi.org/10.1038/leu.2013.81

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