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Hematologic Toxicity of High-Dose Iodine-131–Metaiodobenzylguanidine Therapy for Advanced Neuroblastoma

From the Departments of Pediatrics, Nuclear Medicine, and Epidemiology and Biostatistics, University of California San Francisco, CA; and Department of Pediatrics and Nuclear Medicine, Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, PA

Address reprint requests to Katherine K. Matthay, MD, Department of Pediatrics, Box 0106, University of California, San Francisco, San Francisco, CA 94143; e-mail: matthayk{at}peds.ucsf.edu

PURPOSE: Iodine-131–metaiodobenzylguanidine (¹³¹I-MIBG) has been shown to be active against refractory neuroblastoma. The primary toxicity of ¹³¹I-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 ¹³¹I-MIBG treatment.

PATIENTS AND METHODS: Fifty-three patients with refractory or relapsed neuroblastoma were treated with 18 mCi/kg ¹³¹I-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 x 10³/µL). 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 ¹³¹I-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 ¹³¹I-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.

Supported by funds from the National Institutes of Health (P01 CA81403, 2MO1 RR01271 to UCSF Pediatric Clinical Research Center, and M01-RR00240 to the Children's Hospital of Philadelphia General Clinical Research Center), the Kasle and Tkalcevik Neuroblastoma Research Fund, the Conner Research Fund, and the Campini Foundation.

Presented in part at the American Society of Clinical Oncology 39th Annual Meeting, Chicago, IL, June 2, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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