131I‐Metaiodobenzylguanidine conditioning regimen in children with neuroblastoma undergoing stem cell transplantation

Radio-labeled 131I-metaiodobenzylguanidine (MIBG) therapy is used in the treatment of highrisk neuroblastoma as a part of conditioning regimen in combination with other chemotherapy agents (1). The maximum-tolerated dose of 131IMIBG is reported as 12 mCi/kg (2, 3). However, mucositis as well as myelosuppression is the major toxicity (4). 131I-MIBG may increase the toxicity of the drug regimen. Herein, we report and discuss 131I-MIBG dose and toxicity in two children that were treated with 131I-MIBG, followed by myeloablative doses of carboplatin, etoposide, and melphalan with stem cell rescue. The first case was a nine-month-old female child who presented with right abdominal palpable mass. She was diagnosed with stage IV neuroblastoma and treated with chemotherapy including cyclophosphamide, vincristine, etoposide, cisplatin, dacarbazine, ifosfamide, and adriamycin for six courses in addition to surgical resection resulting in a 2 cm residual right adrenal mass. She underwent autologous bone marrow transplantation (ABMT), including 100 mCi (10 mCi/kg) 131 I-MIBG treatment on day 21 followed by melphalan 45 mg/m/day on days 8 to 5, etoposide 200 mg/m/day, and carboplatin 300 mg/m/day on day 5 to 2. On day +15, she presented with grade 4 mucositis, diarrhea, and massive gastrointestinal bleeding without any evidence of engraftment. After all vigorous efforts, she died on day +18. The second case was an eight-yr-old girl with stage IV neuroblastoma. She was treated with the same chemotherapy for six courses, and there was a 4-cm residual mass after surgical resection. She received radiotherapy to the residual mass. After the first recurrence from the primary site of tumor with multiple metastases in the abdomen, she was treated with ICE chemoterapy regimen, including ifosfamide, carboplatin, and etoposide and then underwent ABMT with the same conditioning regimen including 100 mCi (3.1 mci/kg) 131-I-MIBG on day 21. On day +7, she developed grade 3–4 mucositis, diarrhea and grade 1 autologous GVHD involving an erythematous skin rash on the face and trunk region. There was no platelet engraftment on day +25 when she developed acute hypertension and intracranial bleeding. She died on day +31. CD34 positive stem cell selection and granulocyte colony stimulating factor supplementation was added to the treatment of the two patients that has shown great efficiency in engraftment and prognosis of the patients with neuroblastoma (5, 6). Treatment with 131I-MIBG in combination with myeloablative chemotherapy and ABMT is reported as a feasible option (3). Indications for 131I-MIBG therapy include the following: (i) if no other treatment is possible (surgery, chemotherapy, external beam radiotherapy), (ii) when at least one-yr survival is expected, (iii) all (or most) identifiable lesions should accumulate tracer on the MIBG scan, and (iv) and a radiation dose of 0.5 cGy/MBq can be delivered to the tumor (7, 8). We used an MIBG conditioning regimen for ABMT. Myelosuppression is the most common toxicity, and non-hematologic toxicity is generally mild but there is no definite correlation between dose and response or toxicity (4). Major non-hematologic toxicities reported as grade 2–3 mucositis, diarrhea, and renal dysfunction. Erythematous skin rash, hematuria, asymptomatic hypothyroidism were the other complications (2, 9). Mucositis is the leading toxicity reported and reached to grade 4 in half of the patients (9). In our patients, major non-hematologic toxicities were mucositis and diarrhea, which was consistent with previous literature. Erythematous skin rash was found to be consistent with GVHD pathologically in our second case. Contrary to our current observation, there