Hematologic toxicity of high-dose iodine-131-metaiodobenzylguanidine therapy for advanced neuroblastoma

J Clin Oncol. 2004 Jun 15;22(12):2452-60. doi: 10.1200/JCO.2004.08.058.

Abstract

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 x 10(3)/microL). 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 <or=.04). In patients who did not require AHSCT, bone marrow disease predicted longer periods of neutropenia and platelet transfusion dependence (P <or=.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 <or=.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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Iodobenzylguanidine / administration & dosage*
  • 3-Iodobenzylguanidine / adverse effects*
  • Adolescent
  • Adult
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects*
  • Child
  • Child, Preschool
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Infant
  • Iodine Radioisotopes / therapeutic use
  • Male
  • Neuroblastoma / drug therapy*
  • Neutropenia / chemically induced
  • Neutropenia / therapy
  • Radiopharmaceuticals / administration & dosage*
  • Radiopharmaceuticals / adverse effects*
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / therapy
  • Transplantation, Autologous

Substances

  • Antineoplastic Agents
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • 3-Iodobenzylguanidine