Optimising therapy with ¹³¹I-MIBG for neuroblastoma patients and for neuroblastoma patients with intraspinal extension

Neuroblastoma (NBL) is the most common extra cranial solid tumor of childhood, derived from the sympathetic nervous system. NBL accounts for 8-10% of all childhood cancers, but is responsible for more than 15% of childhood cancer deaths.
The prognosis of patients with high risk NBL is still poor, there is need for new and innovative treatment strategies. Clinical data from studies incorporating ¹³¹I-MIBG for NBL patients are promising. However, the optimal timing, dosing of ¹³¹I-MIBG and the optimal combination with chemotherapy and MAT ASCT for the administration of this therapy remains to be debated. The research presented in this thesis focused on optimizing therapy with ¹³¹I-MIBG for NBL patients in various phase II studies in both relapsed/refractory and newly diagnosed NBL patients. Furthermore, a Cochrane review of the literature was performed on ¹³¹I-MIBG therapy in newly diagnosed high-risk NBL patients. As patients with high-risk NBL receive many treatment modalities (especially ¹³¹I-MIBG) that can cause myelosuppression, an additional study was performed, collecting retrospective data on two cohorts of high-risk NBL patients looking specifically at autologous stem cell harvesting and hematological reconstitution following MAT ASCT. The hematological toxicity, causes mainly thrombocytopenia, we analyzed the stored autologous stem cell harvests looking at the CD34+/41+ megakaryocyte precursors in the transplant.
The second topic of this thesis concentrates on characterizing NBL patients with intraspinal extension and their treatment- and associated health problems. These patients have a relatively high survival rate compared to other NBL patients. The optimal treatment strategy for this group of patients has yet to be deciphered. In light of this, we have analyzed the frequency and severity of long term health problems in these patients and have performed a review of the literature.