BACKGROUND: Sera from healthy individuals contain natural IgM antibodies (anti-NB-Ab) cytotoxic to neuroblastoma (NB) cells. In contrast to healthy children the prevalence of anti-NB-Ab in sera of NB patients is low. Binding of anti-NB-Ab to the NB cell surface leads to activation of complement in vitro. In vivo the injection of the purified IgM fraction from a cytotoxic blood donor results in complete growth arrest of NB xenografts in nude rats. Preliminary results from a phase I/II study to evaluate the pharmacokinetics and side effects of a therapy with anti-NB-Ab are presented here. PATIENTS: Included in this study are patients with NB stage 4 according to INSS with relapse or non-responders to therapy according to the GPOH-NB-therapy protocol. The patients are negative for anti-NB-Ab and are older than one year. METHODS: The therapy is based on a complete exchange of the anti-NB-Ab negative patient serum against serum from an anti-NB-Ab positive ABO-compatible donor by means of plasmapheresis. RESULTS: Up to now, 14 cycles of plasmapheresis have been carried out in 6 NB patients. In 13 of 14 therapy cycles a significant increase in serum toxicity could be observed. Severe side effects have not been seen except a catheter associated thrombosis which was reversible under heparin treatment. After plasmapheresis, pain in the tumor site or regions of metastasis did occur regularly. In some cases temporary elevation of body temperature occurred. One patient had a reduced MIBG uptake after therapy. Tumor necrosis was observed in 2 patients. Three patients showed tumor progress. CONCLUSION: Immunotherapy of NB in children by serum exchange using anti-NB-Ab positive ABO-compatible donor serum is feasible without major side effects and leads to a significant increase of serum toxicity against NB cells.
