Thesis Esther van Wezel

On 28 April 2016 Esther van Wezel defended her thesis 'Minimal residual disease monitoring in neuroblastoma' at the University of Amsterdam.

Promotor: Prof CE van der Schoot PhD and prof HN Caron PhD
Co-promotor: GAM Tytgat PhD

The research for this thesis was conducted at the Dept of Experimental Immunohematology of Sanquin Research. The research was financially supported by Koningin Wilhelmina Fonds, Dutch Cancer Society (UVA 2010−4738).


The presence of metastatic spread at diagnosis is the most important factor in determining outcome in neuroblastoma. Despite intensive treatment, relapse frequently occurs and only approximately 40% of children remain long term disease-free. Bone marrow is a frequent site of recurrent disease. 
Minimal residual disease (MRD) is the term used to describe small numbers of tumor cells remaining in blood or bone marrow during or after treatment, which are below the limits of detection using morphological assessment. Real-time quantitative PCR is a highly sensitive technique to detect MRD. The studies presented in the first part of the thesis focused on improving MRD detection. We describe that patient-specific DNA markers are reliable disease markers, that circulating tumor DNA can be of additive value in disease monitoring and we identified markers specific for the detection of mesenchymal type neuroblastoma cells. In the second part of the thesis the clinical significance of MRD detection was studied. Detection of high levels of neuroblastoma mRNA in patients with localized disease was associated with an unfavorable outcome, therefore for these patients a more careful follow-up is advisable. MRD detection in high risk neuroblastoma is currently being studied in a large international prospective study. An interim analysis of this study revealed that high levels of neuroblastoma mRNA in bone marrow at diagnosis was associated with a poor outcome. Bone marrow response after completion of induction chemotherapy was not associated with a better outcome. However, more patients need to be included and the follow-up time should be increased.