Inclusion Criteria:

- Age: Patients must be >1 year and < 30 years of age when registered on study.

- Diagnosis: Patients must have a diagnosis of neuroblastoma either by histologic
verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow
with increased urinary catecholamines.

- Disease status: Patients must have high-risk neuroblastoma with at least ONE of the
following:

1. Recurrent/progressive disease at any time. Biopsy not required, even if partial
response to intervening therapy except in patients with only one site of
MIBG-avid disease that has been radiated within the preceding two months. Such
patients require biopsy confirmation of residual active disease, with positive
bone marrow biopsy being adequate confirmation of residual active disease.

2. Refractory disease (i.e. less than a partial response to frontline therapy,
including a minimum of 4 cycles of induction chemotherapy). No biopsy is
required for eligibility for this study.

3. Persistent disease after at least a partial response to frontline therapy (i.e.
patient has had at least a partial response to frontline therapy but still has
residual disease by MIBG scan, CT/MRI, or bone marrow). Patients in this
category are REQUIRED to have a biopsy (bone marrow biopsy included) of at least
one residual site demonstrating viable neuroblastoma.

- 131I-MIBG Uptake: Patients must have evidence of MIBG uptake into tumor at ≥ one site
within 4 weeks prior to entry on study and subsequent to any intervening therapy.

- Hematopoietic stem cells: Patients must have an adequate unpurged peripheral blood
hematopoietic stem cell product, with a minimum of 2 X 106 CD34+ cells/kg available.
Having a back-up of 2.0 x 106 viable CD34+ cells/kg unpurged PBSC is recommended but
not required. The use of purged stem cells or autologous bone marrow as donor source
is not allowed. The use of PBSC from an identical twin is allowed.

- Performance and life expectancy: Must have a life expectancy of at least 6 weeks and
a Lansky or Karnofsky score of at least 60.

- Prior therapy: Patients must have fully recovered from the acute toxic effects of all
prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

1. Myelosuppressive chemotherapy and/or biologics: Patients are not required to
complete re-induction chemotherapy prior to study entry following relapse. Last
dose of any myelosuppressive or biologic therapy was given at least 2 weeks
before the start date for irinotecan on this protocol.

2. Radiation: Patients must not have received radiation for a minimum of two weeks
prior to study entry. Patients who received radiation to the only site of
MIBG-avid disease within two months of study entry require biopsy confirmation
of residual active disease, with positive bone marrow biopsy being adequate
confirmation of residual active disease. A minimum of 3 months is required
following prior large field radiation therapy (i.e. craniospinal therapy, total
lung, > 50% marrow space). Patients are excluded if they have received whole
abdominal radiation or TBI (total body irradiation).

3. Stem Cell Transplant (SCT): Patients are eligible three months after autologous
stem cell transplant. Patients status post-allogeneic stem cell transplant are
excluded. Must meet adequate bone marrow function definition (see organ
function requirements, below) post-myeloablative therapy.

4. Prior 131I-MIBG therapy: Patients may have received prior MIBG therapy, though
cumulative lifetime dose should not exceed 18 mCi/kg prior to study entry.
Patients must not have received MIBG in combination with irinotecan. For
patients previously treated with MIBG, at least 6 months must have elapsed since
last MIBG therapy.

5. Growth factor(s): All cytokines or hematopoietic growth factors must be
discontinued a minimum of 7 days prior to the start date for irinotecan on this
protocol.

6. Prior irinotecan and vincristine therapy: are allowed, subject to recovery of
adequate bone marrow function as specified in the protocol.

- Concomitant Therapy Restrictions: Patients must not be receiving any other
anti-cancer agents or radiotherapy at the time of study entry or while on study.
Enzyme-inducing anticonvulsants (phenobarbital, phenytoin, carbamazepine) must not be
used as these may interfere with irinotecan metabolism. Non-enzyme inducing
anticonvulsants (Keppra, etc.) can be used after discussion with study chair. The
use of high dose dexamethasone and the use of aprepitant as antiemetics is not
recommended due to effects on irinotecan metabolism.

- Hematologic function: a. ANC: > 750/uL (no hematopoietic growth factors within 7
days of the start date for irinotecan on this protocol) b. Platelet count: >
50,000/µl, transfusion independent (defined as no platelet transfusion for one week).

c. These criteria must be met by all patients, regardless of bone marrow involvement
with tumor.

- Renal function: a. Glomerular Filtration Rate (GFR) or 12-24hr Creatinine Clearance
>= 60 ml/min/1.73 m², OR b. Age-adjusted serum creatinine < 1.5 x normal for age (see
below):

Age Maximum Serum Creatinine (mg/dL) < 5 years 0.8 > 5 and < 10 years 1.0 > 10 and < 15
years 1.2 > 15 years 1.5

- Liver function:a. Total bilirubin <= 1.5 x normal for age, and b. SGPT (ALT) and SGOT
(AST) < 3 x upper limit of normal

- Cardiac function: Normal ejection fraction (>=55%) documented by either
echocardiogram or radionuclide MUGA evaluation OR normal fractional shortening (>=
27%) documented by echocardiogram.

- Lung function: Normal lung function with no dyspnea at rest, exercise intolerance,
pleural effusion or oxygen requirement.

- Reproductive function: All post-menarchal females must have a negative urine or serum
beta-HCG. Males and females of reproductive age and childbearing potential must use
effective contraception for the duration of their participation.

- Coexisting medical conditions: Patients with other ongoing serious medical issues
must be approved by the study chair prior to registration.

Exclusion Criteria:

- Pregnant or lactating.

- Patients status post-ALLOGENEIC stem cell transplant are NOT eligible.

- Patients who, in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study.

- Patients with disease of any major organ system that would compromise their ability
to withstand therapy.

- Patients who are on hemodialysis.

- Patients with a documented allergy to 3rd generation cephalosporins.

- Patients must not have active diarrhea (defined as > Grade 2 per CTCAE v4 [ Grade 2 =
increase of 4-6 stools/day over baseline] ).

- Patients with an active or uncontrolled infection, including C. difficile, of > grade
3 per CTCAE v4. Patients on prolonged antifungal therapy are eligible if they are
culture and biopsy negative in suspected radiographic lesions and meet other organ
function criteria.

- Patients and/or families who are physically and psychologically unable to cooperate
with the radiation safety isolation.

- Patients who have received prior total body or whole abdominal radiation.

- Patients who have received prior 131I-MIBG therapy in combination with irinotecan.