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The reliability of bone marrow cytology as response criterion in metastatic neuroblastoma
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  • Roswitha Schumacher-Kuckelkorn,
  • Ayad Atra,
  • Maria Luisa Belli,
  • Gerda den Engelsman,
  • Paul Fréneaux,
  • Arnaud Gauthier,
  • Anja Heijlaerts-Klever,
  • Francesca Scuderi,
  • Leonor Senent Peris,
  • Sanjay Tewari,
  • Ondrej Zapletal,
  • Angela Ernst,
  • Frank Berthold
Roswitha Schumacher-Kuckelkorn
Childrens Hospital University of Cologne
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Ayad Atra
St George's University Hospitals NHS Foundation Trust
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Maria Luisa Belli
Istituto Giannina Gaslini
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Gerda den Engelsman
Prinses Maxima Centrum voor Kinderoncologie
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Paul Fréneaux
Institut Curie
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Arnaud Gauthier
Institut Curie
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Anja Heijlaerts-Klever
Prinses Maxima Centrum voor Kinderoncologie
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Francesca Scuderi
Istituto Giannina Gaslini
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Leonor Senent Peris
La Fe University and Polytechnic Hospital
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Sanjay Tewari
Royal Marsden NHS Foundation Trust
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Ondrej Zapletal
University Hospital Brno Children's Hospital
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Angela Ernst
University Hospital Cologne
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Frank Berthold
Childrens Hospital University of Cologne
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Abstract

Background: The quantitative assessment of neuroblastoma cell content in bone marrow aspirates for response evaluation has been introduced recently. Data on the concordance of interobserver reports are lacking so far. Methods: Investigators of seven European countries representing national reference or large oncological centres convened in 2016. They agreed to quantitatively assess routine bone marrow smears of the participating institutions and to discuss the discrepant results in joint meetings. Results From 2017 through 2019, three cytology rounds with 24, 28, and 28 bone marrow samples were run evaluating the representativity of the smears (yes/(restricted)/no) and the presence of tumors cells (yes/no and %). The comparison of the reports using κ (Fleiss) and α (Krippendorff) statistics demonstrated no robust reliabilities. The agreement on the representativity was moderate to poor, on the presence of tumor cells moderate to good and on the percentage of tumor cells slight to moderate. Though the unquestioned value of cytology to detect even tiny metastatic cells in bone marrow, the investigators unanimously agreed that a reliable quantification of the tumor cell content in bone marrow smears is unrealistic. For the key issue of representativity, a new practical definition was developed. Conclusion For any work with bone marrow aspirates the representativity of the material is of paramount importance. A practical definition is proposed. A reliable quantitative cytological assessment of tumor cell content in bone marrow aspirates is not feasible in metastatic neuroblastoma. Therefore its use as response criterion should be re-considered.

Peer review status:UNDER REVIEW

09 Sep 2020Submitted to Pediatric Blood & Cancer
09 Sep 2020Assigned to Editor
09 Sep 2020Submission Checks Completed
12 Sep 2020Reviewer(s) Assigned
29 Sep 2020Review(s) Completed, Editorial Evaluation Pending