Hematologic Toxicity of High-Dose Iodine-131–Metaiodobenzylguanidine Therapy for Advanced Neuroblastoma Steven G. DuBois, Julia Messina, John M. Maris, John Huberty, David V. Glidden, Janet Veatch, Martin Charron, Randall Hawkins, and Katherine K. Matthay A B S T R A C T Purpose Iodine-131–metaiodobenzylguanidine ( 131 I-MIBG) has been shown to be active against refractory neuroblastoma. The primary toxicity of 131 I-MIBG is myelosuppression, which might necessitate autologous hematopoietic stem-cell transplantation (AHSCT). The goal of this study was to determine risk factors for myelosuppression and the need for AHSCT after 131 I-MIBG treatment. Patients and Methods Fifty-three patients with refractory or relapsed neuroblastoma were treated with 18 mCi/kg 131 I-MIBG on a phase I/II protocol. The median whole-body radiation dose was 2.92 Gy. Results Almost all patients required at least one platelet (96%) or red cell (91%) transfusion and most patients (79%) developed neutropenia ( 0.5  10 3 /L). Patients reached platelet nadir earlier than neutrophil nadir (P  .0001). Earlier platelet nadir correlated with bone marrow tumor, more extensive bone involvement, higher whole-body radiation dose, and longer time from diagnosis to 131 I-MIBG therapy (P  .04). In patients who did not require AHSCT, bone marrow disease predicted longer periods of neutropenia and platelet transfusion dependence (P  .03). Nineteen patients (36%) received AHSCT for prolonged myelosuppression. Of patients who received AHSCT, 100% recovered neutrophils, 73% recovered red cells, and 60% recovered platelets. Failure to recover red cells or platelets correlated with higher whole-body radiation dose (P  .04). Conclusion These results demonstrate the substantial hematotoxicity associated with high-dose 131 I-MIBG therapy, with severe thrombocytopenia an early and nearly universal finding. Bone marrow tumor at time of treatment was the most useful predictor of hematotoxicity, whereas whole-body radiation dose was the most useful predictor of failure to recover platelets after AHSCT. J Clin Oncol 22:2452-2460. © 2004 by American Society of Clinical Oncology INTRODUCTION Neuroblastoma is the most common extracra- nial solid cancer in children. The majority of patients present with metastatic disease at diagnosis. Despite recent improvements in outcome with intensification of therapy for metastatic neuroblastoma, the majority of pa- tients will ultimately experience relapse and die as a result of disease. 1 Metaiodobenzylguanidine (MIBG) is a guanethidine derivative with specific af- finity for neural crest tissues. 2 MIBG la- beled with iodine-131 ( 131 I-MIBG) has been shown to be active against neuroblas- toma, with one third to one half of pa- tients with refractory or relapsed disease having some response. 3-5 Although 131 I- MIBG typically has been used as a single agent for patients with refractory or re- lapsed disease, several groups have used 131 I-MIBG combined with chemotherapy earlier in the course of disease. 4,6,7 With this expanding role, an understanding of the toxicity of 131 I-MIBG has become in- creasingly important. In a phase I trial of 131 I-MIBG for ad- vanced neuroblastoma, the primary toxicity From the Departments of Pediatrics, Nuclear Medicine, and Epidemiology and Biostatistics, University of Califor- nia San Francisco, CA; and Department of Pediatrics and Nuclear Medicine, Children’s Hospital of Philadelphia and the University of Pennsylvania, Philadel- phia, PA. Submitted August 8, 2003; accepted March 31, 2004. Supported by funds from the National Institutes of Health (P01 CA81403, 2MO1 RR01271 to UCSF Pediatric Clin- ical Research Center, and M01- RR00240 to the Children’s Hospital of Philadelphia General Clinical Research Center), the Kasle and Tkalcevik Neuro- blastoma Research Fund, the Conner Research Fund, and the Campini Foundation. Presented in part at the American Soci- ety of Clinical Oncology 39th Annual Meeting, Chicago, IL, June 2, 2003. Authors’ disclosures of potential con- flicts of interest are found at the end of this article. Address reprint requests to Katherine K. Matthay, MD, Department of Pediat- rics, Box 0106, University of California, San Francisco, San Francisco, CA 94143; e-mail: matthayk@ peds.ucsf.edu. © 2004 by American Society of Clinical Oncology 0732-183X/04/2212-2452/$20.00 DOI: 10.1200/JCO.2004.08.058 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 22  NUMBER 12  JUNE 15 2004 2452 Copyright © 2004 by the American Society of Clinical Oncology. All rights reserved. Downloaded from www.jco.org at UNIV SOUTHERN CALIF NORRIS MEDICAL LIBRARY on May 30, 2005 .