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Cancer. 2017 Apr 1;123(7):1095-1105. doi: 10.1002/cncr.30380. Epub 2016 Dec 16.

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.

Author information

Children's Cancer Research Group, Leeds Institute of Cancer and Pathology, St James's University Hospital, Leeds, United Kingdom.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo and Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California.
CCRI, Children's Cancer Research Institute, Vienna, Austria.
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California.
Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.
Children's Cancer Institute for Medical Research, Cancer Research Centre, Sydney, New South Wales, Australia.
Department of Pediatrics, School of Medicine, University of Washington, Seattle Children's Hospital, Seattle, Washington.
Department of Pediatric Oncology and Hematology, Center for Integrated Oncology, University of Cologne, Cologne, Germany.



The current study was conducted to expedite international standardized reporting of bone marrow disease in children with neuroblastoma and to improve equivalence of care.


A multidisciplinary International Neuroblastoma Response Criteria Bone Marrow Working Group was convened by the US National Cancer Institute in January 2012 with representation from Europe, North America, and Australia. Practical transferable recommendations to standardize the reporting of bone marrow disease were developed.


To the authors' knowledge, the current study is the first to comprehensively present consensus criteria for the collection, analysis, and reporting of the percentage area of bone marrow parenchyma occupied by tumor cells in trephine-biopsies. The quantitative analysis of neuroblastoma content in bone marrow aspirates by immunocytology and reverse transcriptase-quantitative polymerase chain reaction are revised. The inclusion of paired-like homeobox 2b (PHOX2B) for immunohistochemistry and reverse transcriptase-quantitative polymerase chain reaction is recommended. Recommendations for recording bone marrow response are provided. The authors endorse the quantitative assessment of neuroblastoma cell content in bilateral core needle biopsies-trephines and aspirates in all children with neuroblastoma, with the exception of infants, in whom the evaluation of aspirates alone is advised. It is interesting to note that 5% disease is accepted as an internationally achievable level for disease assessment.


The quantitative assessment of neuroblastoma cells is recommended to provide data from which evidence-based numerical criteria for the reporting of bone marrow response can be realized. This is particularly important in the minimal disease setting and when neuroblastoma detection in bone marrow is intermittent, where clinical impact has yet to be validated. The wide adoption of these harmonized criteria will enhance the ability to compare outcomes from different trials and facilitate collaborative trial design. Cancer 2017;123:1095-1105. © 2016 American Cancer Society.


aspirates; biopsies; bone marrow; consensus; immunocytology; immunohistochemistry; neuroblastoma; quantitative; reverse transcriptase-quantitative polymerase chain reaction (RTqPCR); trephines

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