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


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).


CONCLUSIONS
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.
DuBois
Steven G
SG
Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
Messina
Julia
J
Maris
John M
JM
Huberty
John
J
Glidden
David V
DV
Veatch
Janet
J
Charron
Martin
M
Hawkins
Randall
R
Matthay
Katherine K
KK
D019797:3-Iodobenzylguanidine / Q000008:administration & dosage* / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000628:therapy; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000009:adverse effects*; D013921:Thrombocytopenia / Q000139:chemically induced / Q000628:therapy; D014182:Transplantation, Autologous
D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine