Prognostic value of initial bone marrow disease detection by multiparameter flow cytometry in children with neuroblastoma
- 116 Downloads
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.
KeywordsNeuroblastoma 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.
- Beiske K et al (2009) Consensus criteria for sensitive detection of minimal neuroblastoma cells in bone marrow, blood and stem cell preparations by immunocytology and QRT-PCR: recommendations by the International Neuroblastoma Risk Group Task Force. Br J Cancer 100:1627–1637. https://doi.org/10.1038/sj.bjc.6605029 CrossRefGoogle Scholar
- Bozzi F, Gambirasio F, Luksch R, Collini P, Brando B, Fossati-Bellani F (2006) Detecting CD56+/NB84+/CD45- immunophenotype in the bone marrow of patients with metastatic neuroblastoma using flow cytometry. Anticancer Res 26:3281–3287Google Scholar
- Bozzi F et al (2008) Flow cytometric phenotype of rhabdomyosarcoma bone marrow metastatic cells and its implication in differential diagnosis with neuroblastoma. Anticancer Res 28:1565–1569Google Scholar
- Burchill SA et al (2017) Recommendations for the standardization of bone marrow disease assessment and reporting in children with neuroblastoma on behalf of the International Neuroblastoma Response Criteria Bone Marrow Working Group. Cancer 123:1095–1105. https://doi.org/10.1002/cncr.30380 CrossRefGoogle Scholar
- Cheung IY, Cheung NK (2001) Quantitation of marrow disease in neuroblastoma by real-time reverse transcription-PCR. Clin Cancer Res 7:1698–1705Google Scholar
- Gautam U, Srinivasan R, Rajwanshi A, Bansal D, Marwaha RK (2008) Comparative evaluation of flow-cytometric immunophenotyping and immunocytochemistry in the categorization of malignant small round cell tumors in fine-needle aspiration cytologic specimens. Cancer 114:494–503. https://doi.org/10.1002/cncr.23948 CrossRefGoogle Scholar
- Hartmann O et al (1999) Prognostic factors in metastatic neuroblastoma in patients over 1 year of age treated with high-dose chemotherapy and stem cell transplantation: a multivariate analysis in 218 patients treated in a single institution. Bone Marrow Transpl 23:789–795. https://doi.org/10.1038/sj.bmt.1701737 CrossRefGoogle Scholar
- Ifversen MR, Kagedal B, Christensen LD, Rechnitzer C, Petersen BL, Heilmann C (2005) Comparison of immunocytochemistry, real-time quantitative RT-PCR and flow cytometry for detection of minimal residual disease in neuroblastoma. Int J Oncol 27:121–129Google Scholar