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

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Abstract

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 × 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.

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