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Pilot Study of Iodine-131–Metaiodobenzylguanidine in Combination With Myeloablative Chemotherapy and Autologous Stem-Cell Support for the Treatment of Neuroblastoma

From the Blood and Marrow Stem Cell Transplantation Program, Division of Pediatric Hematology-Oncology, and Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor, MI; and Department of Pediatrics, University of California San Francisco, San Francisco, CA.

Address reprints requests to Gregory Yanik, MD, B1-208 Cancer Center, Blood and Marrow Stem Cell Transplantation Program, University of Michigan Medical Center, 1500 E Medical Center Dr, Ann Arbor, MI 48109; email: gyanik{at}umich.edu

PURPOSE: The survival for children with relapsed or metastatic neuroblastoma remains poor. More effective regimens with acceptable toxicity are required to improve prognosis. Iodine-131–metaiodobenzylguanidine (¹³¹I-MIBG) selectively targets radiation to catecholamine-producing cells, including neuroblastoma cells. A pilot study was performed to examine the feasibility of a novel regimen combining ¹³¹I-MIBG and myeloablative chemotherapy with autologous stem-cell rescue.

PATIENTS AND METHODS: Twelve patients with neuroblastoma were treated after relapse (five patients) or after induction therapy (seven patients). Eight patients had metastatic and four had localized disease at the time of therapy. All patients received ¹³¹I-MIBG 12 mCi/kg on day -21, followed by carboplatin (1,500 mg/m²), etoposide (800 mg/m²), and melphalan (210 mg/m²) administered from day -7 to day -4. Autologous peripheral-blood stem cells or bone marrow were infused on day 0. Engraftment, toxicity, and response rates were evaluated.

RESULTS: The ¹³¹I-MIBG infusion and myeloablative chemotherapy were both well tolerated. Grade 2 to 3 oral mucositis was the predominant nonhematopoietic toxicity, occurring in all patients. The median times to neutrophil ( 0.5 x 10³/µL) and platelet ( 20 x 10³/µL) engraftment were 10 and 28 days, respectively. For the eight patients treated with metastatic disease, three achieved complete response and two had partial responses by day 100 after transplantation.

CONCLUSION: Treatment with ¹³¹I-MIBG in combination with myeloablative chemotherapy and hematopoietic stem-cell rescue is feasible with acceptable toxicity. Future study is warranted to examine the efficacy of this novel therapy.

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