Megatherapy combining I131 metaiodobenzylguanidine and high-dose chemotherapy with haematopoietic progenitor cell rescue for neuroblastoma

Abstract

Summary:Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still has very poor prognosis which is estimated at 25%. Metabolic radiotherapy with I 131 MIBG appears a feasible option to enhance the effects of chemotherapy. Seventeen patients having MIBGpositive residual disease received 4.1-11.1 mCi/kg of I 131 MIBG 7-10 days before initiating the high-dose chemotherapy cycle consisting of busulphan 16 mg/kg and melphalan 140 mg/m 2 followed by PBSC infusion. We compared the toxicity in these patients to that seen in 15 control subjects with neuroblastoma who underwent a PBSC transplant without MIBG therapy. We observed greater toxic involvement of the gastrointestinal system in children treated with I strategy includes inductive chemotherapy, mainly based on ozaphorines and platine derivatives followed by surgery and a consolidation phase including megatherapy with stem cell rescue. Conditioning regimens combining high-dose chemotherapy with total body irradiation have been abandoned due to unsatisfactory results and severe late effects. In a Children's Cancer Group (CCG) study, the event-free survival (EFS) of children receiving high-dose (HD) chemotherapy with peripheral blood stem cell transplantation (PBSC) rescue was 34% reaching 46% when followed by further therapy with 13 cis-retinoic acid treatment. 1 Targeted radiotherapy with I 131 metaiodobenzylguanidine (MIBG) has proven to be active in advanced neuroblastoma (NB) and insertion in the megatherapy regimen is promising. In fact, I 131 MIBG, that concentrates in the neuroblastoma cells, is potentially capable of selectively delivering a substantial radiation dose to neoplastic cells while sparing normal tissues. We report on the feasibility of this approach in 17 patients with advanced NB. Fifteen children with NB receiving a similar myeloablative conditioning regimen without I 131 MIBG are evaluated and reported as controls. Our experience suggests that including I 131 MIBG in the conditioning regimen followed by PBSC rescue in children taking up MIBG is a feasible therapeutic strategy, although attention should be paid to avoiding lung complications. Patients and methods Patients' characteristics and first line therapyFrom October 1994 to February 2000 17 patients suffering from either stage 3 (one patient) or 4 (16 patients) neuroblastoma and having positive MIBG residual disease were treated with MIBG megatherapy followed by high-dose chemotherapy with PBSC rescue. Ten were females and seven were males. Median age at diagnosis was 3 years (range 1-9). Median time between diagnosis and megatherapy was 7 months (range 4-46). NB origin was adrenal in seven cases, retroperitoneal gangliar in seven cases, abdominal in two, and unknown in one.

Adult-onset adrenal ganglioneuroblastoma — Bone metastasis two years after surgery: Report of a case

“…Despite recent advances in treatment, neuroblastoma remains a relatively lethal tumor, accounting for 10% of pediatric cancers but 15% of cancer deaths in children. 15 In the last few years, metabolic radiotherapy including 131 I-meta-iodobenzylguanidine scintigraphy has been used in the treatment of advanced neuroblastomas in order to enhance the effects of chemotherapy with peripheral blood progenitor cell transplantation (PBSCT), 16 though it has not been accepted as the preferred therapy.…”

28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures

“…38 Preliminary results of the association of melphalan with TBI and MIBG demonstrate the feasibility of such a regimen. [39][40][41] High doses of MIBG alone or in combination with topotecan 42 or other radiosensitizing agents such as CDDP 43,44 followed by PBSCR have been piloted with early promising results in poor responding or relapse patients. 9.…”

Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: Results of SMC NB-2004 study

“…Incorporation of high-dose 131 I-MIBG treatment into HDCT/auto-SCT might be an option although it also results in late effects. [10][11][12][13][14][15] Matthay et al 15 showed that incorporation of high-dose 131 I-MIBG treatment into HDCT/auto-SCT was feasible and effective in patients with refractory neuroblastoma. However, no studies to date have incorporated high-dose 131 I-MIBG treatment into tandem HDCT/ auto-SCT for treating newly diagnosed high-risk patients.…”