Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin

Inclusion Criteria:

• Diagnosis of neuroblastoma (ICD-O morphology 9500/3) or ganglioneuroblastoma by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites meeting 1 of the following staging criteria:

  • Newly diagnosed International Neuroblastoma Staging System (INSS) stage 4 disease meeting 1 of the following criteria:

    • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age ≥ 365 days regardless of additional biologic features
    • Age > 18 months (> 547 days) regardless of biologic features
    • Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features: MYCN amplification, unfavorable pathology, and/or DNA index = 1, or any biologic feature that is indeterminant, unsatisfactory, or unknown

  • Newly diagnosed INSS stage 3 disease meeting 1 of the following criteria:

    • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age ≥ 365 days, regardless of additional biologic features
    • Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status
  • Newly diagnosed INSS stage 2a/2b with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age ≥ 365 days, regardless of additional biologic features
  • Age ≥ 365 days initially diagnosed with INSS stage 1, 2, or 4S who progressed (within the past 4 weeks) to a stage 4 without interval chemotherapy
  • No patients aged 12-18 months with INSS stage 4 and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1)
• Must be enrolled onto ANBL00B1 biologic study
• Must have ≥ 1 "MIBG-avid target lesion" present on MIBG scan in the past 4 weeks
• Total bilirubin ≤1.5 times upper limit of normal (ULN)
• AST or ALT ≤ 10 times ULN

• Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age and/or gender as follows:

  • ≤ 0.6 mg/dL (1 to < 2 years of age)
  • ≤ 0.8 mg/dL (2 to < 6 years of age)
  • ≤ 1.0 mg/dL (6 to < 10 years of age)
  • ≤ 1.2 mg/dL (10 to < 13 years of age)
  • ≤ 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
  • ≤ 1.7 mg/dL (male) or 1.4 mg/dL (female) ( ≥ 16 years of age)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 50% by radionuclide evaluation

• Able to tolerate peripheral blood stem cell (PBSC) collection

  • No contraindications to PBSC collection including weight, size, or physical condition that would preclude apheresis

• No prior systemic therapy

  • Localized emergency radiotherapy to sites of life-threatening or function-threatening disease and ≥ 1 measurable lesion is not irradiated
  • No more than 1 course of chemotherapy per low- or intermediate-risk neuroblastoma therapy before determination of MYCN amplification and histology

• No local radiotherapy that includes any of the following:

  • 1,200 cGy to more than 33% of both kidneys

    • Patient must have ≥ 1 kidney that has not exceeded the dose/volume of radiation listed
  • 1,800 cGy to more than 30% of liver and/or 900cGy to more than 50% of liver
• No other concurrent cancer chemotherapy or immunomodulating agents (including steroids)