title: Treatment of neuroblastoma stage 4 with 131I-meta-iodo-benzylguanidine, high-dose chemotherapy and immunotherapy. A pilot study.
abstract: Disseminated neuroblastoma after infancy has a prognosis of approximately 10-20% with conventional therapy. We investigated the role of high-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) rescue in combination with 131I-metaiodobenzylguanidine ([131I-m]IBG). 11 children with neuroblastoma stage 4 were pretreated within the German Neuroblastoma Trial NB90 and included in a high-dose concept for consolidation. Remission was documented by ultrasound, CT, NMR, or [123I-m]IBG scanning. HDCT was a combination of melphalan (180 mg/m2), carboplatin (1,500 mg/m2) and etoposide (40 mg/kg). All children were treated by [131I-m]IBG (0.58 GBq/kg) prior to high-dose treatment. All 11 children were additionally treated with antiGD2 murine- or chimeric-antibody (ch14.18). 4 children had no change to their remission status but three achieved a complete response (from a partial response to first line) and one a partial response (from no response to first line). The other 3 children progressed, 2 dying of their disease. Using Kaplan-Meier analysis, the probability of progression-free survival was 0.70 +/- 0.15 with a median observation time of 19 months. 9/11 children are alive, 8 without progression or relapse, whilst 2 have died of their disease. The combination of mIBG plus high-dose chemotherapy with PBSC support supplemented by immunotherapy with antiGD2 antibody appears to be a feasible and effective treatment regimen for disseminated neuroblastoma in this limited series. Larger numbers of patients should be treated to confirm these results.
authors.affiliation: Childrens Hospital, University of Tübingen, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Klingebiel
authors.forename: P
authors.initials: P
authors.lastname: Bader
authors.forename: R
authors.initials: R
authors.lastname: Bares
authors.forename: J
authors.initials: J
authors.lastname: Beck
authors.forename: B
authors.initials: B
authors.lastname: Hero
authors.forename: H
authors.initials: H
authors.lastname: Jürgens
authors.forename: P
authors.initials: P
authors.lastname: Lang
authors.forename: D
authors.initials: D
authors.lastname: Niethammer
authors.forename: B
authors.initials: B
authors.lastname: Rath
authors.forename: R
authors.initials: R
authors.lastname: Handgretinger
mesh_terms: D019797:3-Iodobenzylguanidine / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007223:Infant; D009447:Neuroblastoma / Q000188:drug therapy / Q000628:therapy*; D010865:Pilot Projects; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine