Journal of Cancer Research and Clinical Oncology

, Volume 145, Issue 2, pp 535–542 | Cite as

Prognostic value of initial bone marrow disease detection by multiparameter flow cytometry in children with neuroblastoma

  • Alexander PopovEmail author
  • Alexander Druy
  • Egor Shorikov
  • Tatiana Verzhbitskaya
  • Alexander Solodovnikov
  • Leonid Saveliev
  • Godelieve A. M. Tytgat
  • Grigory Tsaur
  • Larisa Fechina
Original Article – Clinical Oncology



Multicolor flow cytometry (MFC) is widely available, fast and has an easy-to perform approach for finding neuroblastoma (NB) cells among normal bone marrow (BM) hematopoietic cells. Aim of the study was to investigate prognostic significance of initial MFC tumor cells’ detection in BM of children with NB.


51 patients (24 boys and 27 girls) aged from 6 days to 15 years (median age 1 year 3 months) with NB were included in the study. BM samples at the time of diagnosis were obtained from 2 to 5 aspiration sites per patient. CD45(−)CD56(+)CD81(+)GD2(+)-cells were evaluated by MFC.


NB cells were detected in BM by FC more frequently compared to conventional cytomorphology (49.0% and 29.4% patients, respectively, р = 0.043). Patients with NB cells detected in BM by MFC had significantly worse event-free survival and cumulative incidence of relapse/progression [0.24(0.08) and 0.60(0.10), respectively] compared to children with negative result of immunophenotyping [0.85(0.07) and 0.12(0.06), respectively, p < 0.001 in both cases]. BM involvement detection by MFC maintained its prognostic significance in various patients groups. In multivariate analysis, immunophenotyping proved to be an independent prognostic factor when analyzed jointly with other NB risk factors. In 42 patients BM involvement was also studied by RQ-PCR for PHOX2B and TH genes expression. Within groups of patients divided by RQ-PCR positivity, MFC-positivity retained prognostic significance.


Thus flow cytometric BM involvement detection has very strong prognostic impact even stronger than RQ-PCR. It could be used in combination with other parameters for the treatment strategy choice in patients with NB.


Neuroblastoma Flow cytometry Bone marrow Prediction of outcome 



This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

Authors declare no relevant conflicts of interests.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Alexander Popov
    • 1
    Email author
  • Alexander Druy
    • 1
    • 2
  • Egor Shorikov
    • 3
  • Tatiana Verzhbitskaya
    • 2
    • 4
  • Alexander Solodovnikov
    • 2
  • Leonid Saveliev
    • 2
    • 4
  • Godelieve A. M. Tytgat
    • 5
    • 6
  • Grigory Tsaur
    • 2
    • 4
  • Larisa Fechina
    • 2
    • 4
  1. 1.Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and ImmunologyMoscowRussian Federation
  2. 2.Research Institute of Medical Cell TechnologiesYekaterinburgRussian Federation
  3. 3.PET-Technology Center of Nuclear MedicineYekaterinburgRussian Federation
  4. 4.Regional Children’s HospitalYekaterinburgRussian Federation
  5. 5.Department of Pediatric OncologyEmma Children’s Hospital (EKZ/AMC)AmsterdamThe Netherlands
  6. 6.Princess Máxima Centre for Pediatric Oncology (PMC)UtrechtThe Netherlands

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