- The tumor showed no MYCN amplification or loss of chromosome 1p, which are associated with a poorer prognosis. It had a near triploid number of chromosomes. - Persisting residual tumors in patients with intermediate-risk neuroblastoma were not associated with progression despite imaging findings, as long as catecholamine levels were not elevated. - Infants under 18 months with Stage 3 neuroblastoma had a significantly better 5-year event-free and overall survival than patients over 18 months.

2. • No MYCNamplification
• Near triploid nmber of chromosomes.
• No loss of chromosome 1p.
{Ambros et al., 2000}
The capacity to undergo regression
LR
Ivs

3. The capacity to undergo maturation
IR
Residual
after
surgery
Persisting residual and maturing tumors in IR Neuroblastoma
patients were not associated with tumor progression, despite
MIBG uptake and/or elevated catecholamines {Marachelian et al.,
2012}.

4. A superior prognosis for infants
Outcome of INSS Stage III Patients From the INRG Database
Number
5-y EFS
P-value 5-y OS
P-value
Stage III 86
< 18 M 850 86%
<0.0001
91%
<0.0001
> 18 M 633 58% 66%
Holly J. et al., Pediatic Blood Cancer 2014
< 18 vs >18 M

5. The most common cancer in infants “<1 year old”
The most common extra-cranial solid cancer in
childhood
Accounts for about 7% of all cancers in children.
The average age diagnosis “18 months”.
90% of cases are diagnosed by age 5.
Very rare in people over the age of 10 years.

6. Non- specific and mimic many childhood illnesses
Site of primary tumor
Local infiltration
Sites of metastatic disease
Metabolic disturbances

7. Abdominal pain, discomfort,
fullness or rarely obstruction.
Cough, dysphagia,
breathlessness, thoracic inlet
obstruction leading to superior
vena caval syndrome.
Horner ’ s syndrome
Some tumors have intra - spinal
and extra - spinal components
(dumb - bell tumors) and it can
lead to cord compression
causing flaccid paralysis and
urinary and bowel disturbances.
bladder or bowel
obstruction.
Site of primary tumor

8. MEDICAL COMPLICATIONS
Patients with bulky or advanced stage disease may be
classified as being at intermediate risk for tumor lysis
syndrome and prophylaxis against the complications
of tumor lysis syndrome may be considered .
Cairo et al., 2010
Tumor
lysis

9. MEDICAL COMPLICATIONS
7 -15 %
 In a review of 99 children with spinal cord involvement, 71 had
residual impairments after a median follow-up of eight years. The
most common impairments in this population were motor function,
scoliosis, and bladder function {Simon et al., 2012}.
 Chemotherapy and laminectomy have equivalent overall survival
outcomes.
 RT is generally reserved for progressive symptoms despite
chemotherapy.
Spinal cord
compressio
n

10. MEDICAL COMPLICATIONS
Opsoclonus
myoclonus
 lower stage and have favorable prognosis for survival
{De Grandis et al., 2009}
 long-term neurologic deficits (e.g., cognitive and motor
delays, language deficits, and behavioral abnormalities).
 Chemotherapy, corticosteroids, and IV immune globulin.
 Symptoms refractory to these treatments may respond to
rituximab . {Battaglia et al., 2012}

11. MEDICAL COMPLICATIONS
Autonomous tumor secretion of VIP that is associated with NB.
VIP secretion can cause abdominal distension and intractable
secretory diarrhea with hypokalemia; these symptoms usually
resolve after removal of the tumor.
The diagnosis is established by the presence of unexplained high-
volume secretory diarrhea and a serum VIP concentration in excess
of 75 pg/Ml.
VIP-producing tumors are more often the less aggressive GNB
and GN rather than undifferentiated neuroblastomas.
Secretory
diarhea

12. Sites of metastatic disease
Orbit
bone
marrow
Bone
lymph
nodes
Skin
Liver
Brain
Skull,
orbits, jaw
and long
bones

13. Laboratory tests
CBC, LDH
NSE
ferritin
LFT, KFT,
electrolytes
Urine
HVA-VMA

14. • a major tissue-binding protein.
• Raised ferritin results from direct secretion by the tumor.
• High levels of ferritin related to poor survival.
• The International Neuroblastoma Risk Group (INRG) recently
analysed the prognostic markers in 1483 stage 3
neuroblastoma patients. Holly et al.; 2014
ferritin

15. NSE
• Enolases are glycolytic enzymes
2 - phosphoglycerate >>> >>> phosphoenolpyruvate.
• Three immunologically distinct subunits: alpha, beta, and gamma.
• Gamma enolase is found in neuron and called NSE.
• Non a specific marker
• increased levels
 Wilms tumor,
 Ewing sarcoma,
 Non- Hodgkin lymphoma,
 Acute leukemia,
 Non - malignant conditions, e.g. brain damage.

16. CT scan/MRI scan confirms site, size, extension,
vascular involvement.
Encasing major blood vessels is a characteristic
feature of neuroblastoma.
CT is the major imaging modality pre - surgery to
demonstrate the relationship between tumor and
blood vessels.

17. MRI scan is important to evaluate for intra - spinal
extensions

18. MIBG scan is positive in about 90% patients and is
an important single tool to identify all disease
sites and to evaluate response
• sensitive and specific.
• Meta-iodobenzylguanidine (MIBG) that contains a small
amount of radioactive iodine.
• MIBG is similar to nor epinephrine.
• The thyroid gland must be protected by the simultaneous
administration of non-radioactive iodine (e.g., potassium
iodide).
• Several hours or days later, the body is scanned with a
special camera to look for areas that picked up the
radioactivity.
• Can be used at higher doses to treat the NB.

19. Bone scan is only useful in MIBG negative
neuroblastoma.
The role of the CT FDG - PET scan needs further
evaluation and is a very promising imaging
modality

20. Biopsies • Needle biopsy
• Bone marrow aspiration and biopsy
Diagnostic criteria
• An unequivocal histological diagnosis from tumor tissue
by light microscopy, with or without
immunohistochemistry, electron microscopy, or
increased urine (or serum) catecholamine’s or their
metabolites.
• Evidence of metastases to bone marrow on an aspirate
or trephine biopsy with concomitant elevation of urinary
or serum catecholamine’s or their metabolites {Brodeur
et al., 1993}.

21. 1. A suprarenal location.
2. Thoracic and retroperitoneal locations.
3. Metastatic involvement of the bonemarrow.
4. Spinal canal involvement.
5. Skin nodules in newborns and infants.
6. Other causes of Opsoclonus-myoclonus syndrome.
Wilms
Hepatoblastoma
Lymphoma Germ cell tumors
soft tissue
sarcoma
LymphomaEwing sarcomaRhabdomyosarcoma
Infantile fibrosarcomaCongenital leukemia Dermoid cyst
Hepatoblastoma
Infections Toxic exposures
Hyperosmolar
non ketotic coma

22. Evans et al described the first staging system for neuroblastoma
and used by the Children ’ s Cancer Group(CCG) in the USA.
1971Involvement of lymph nodes and spread across the midline
St Jude ’ s proposed a surgico - pathological staging system.
Extent of surgery and lymph node involvement 1983
The TNM staging was proposed jointly by the American
joint committee.
Extent of surgery and lymph node involvement 1987

23. International Neuroblastoma staging system (INSS) and
International Neuroblastoma Response Criteria (INRC).
Based on the assessment of resectability and surgical
examination of lymph node involvement
1998
INSS modified
•Post- surgical classification
•Assessment of lymph node involvement
1993

24. • Stage 1:(1X1) Localized tumor confined to the area of origin; complete gross
excision, with or without microscopic residual disease. Representative ipsilateral
and contralateral lymph nodes negative for tumor microscopically (nodes attached
to and removed with the primary tumor may be positive).
• Stage 2a:(1X1) Localized tumor with incomplete gross excision; representative
ipsilateral and non - adherent lymph nodes negative for tumor microscopically.
• Stage 2b:(2X2) Localized tumor with complete or incomplete gross excision;
with ipsilateral non - adherent lymph nodes positive for tumor. Enlarged
contralateral lymph nodes must be negative microscopically.
• Stage 3:(3X3) Unresectable unilateral tumor infiltrating across the midline with
or without regional lymph node involvement; or localized unilateral tumor with
contralateral regional lymph node involvement or midline tumor with bilateral
extension by infiltration (unresectable) or by lymph node involvement.
• Stage 4 Any primary tumor with dissemination to distant lymph nodes, bone, bone
marrow, liver, skin and/or other organs (except as defi ned in stage 4S).
• Stage 4S Localized primary tumor (as defined for stage 1, 2a or 2b) with
dissemination limited to skin, liver and/or bone marrow ‡ (limited to infants less
than one year old).

25. Description of International Neuroblastoma Response Criteria
•Complete Remission (CR): No tumor, no metastases, normal markers.
•Very good Partial Remission (VGPR):
Primary; reduction more than 90%, but less 100%
Metastases; no tumor except bone {all preexisting lesions improved}
Markers; decreased more than 90%
•Partial Remission (PR):
Primary; reduction 50%-90%
Metastases; no new lesions; 50%-90% reduction in measurable sites; 0-1
BM samples positive; bone lesions the same as VGPR.
Markers; decreased 50%-100%
•Mixed Response (MR):No new lesions; more than 50% reduction of any
measurable lesion {primary or metastases} with less than 50% reduction in any
other; less than reduction 25% increase in any existing lesion.
•No Response (NR): No new lesions; less than 50% reduction but less than 25%
increase in any existing lesion.
•Less than PR: No new lesions; less than 50% reduction
•Progressive Disease (PD): Any new lesion; increase of any measurable lesion by
more than 25%; previous negative marrow positive for tumor.

26. • L1: Localized tumor not involving vital structures as
defined by the list of image defined risk factors and
confined to one body compartment.
• L2 :Locoregional tumor with presence of one or more
image defined risk factors.
• M: Distant metastatic disease (except Stage MS).
• MS :Metastatic disease in children younger than 18
months with metastases confined to skin, liver and/or
bone marrow.
INRGSS
•Pre- treatment clinical staging stystem
•It was designed for INRGCS 2009

27. Image defined risk factors in neuroblastic tumors
Neck:
• Tumor encasing carotid and/or vertebral artery and/or internal jugular vein
• Tumor extending to base of skull
• Tumor compressing the trachea
Cervico - thoracic junction:
• Tumor encasing brachial plexus roots
• Tumor encasing subclavian vessels and/or vertebral and/or carotid artery
• Tumor compressing the trachea
Thorax:
• Tumor encasing the aorta and/or major branches
• Tumor compressing the trachea and/or principal bronchi
• Lower mediastinal tumor, infi ltrating the costo - vertebral junction between
T9 and T12
Thoraco - abdominal:
• Tumor encasing the aorta and/or vena cava

28. Image defined risk factors in neuroblastic tumors
Abdomen/pelvis:
• Tumor infiltrating the porta hepatis and/or the hepatoduodenal ligament
• Tumor encasing branches of the superior mesenteric artery at the mesenteric root
• Tumor encasing the origin of the coeliac axis, and/or of the superior mesenteric artery
• Tumor invading one or both renal pedicles
• Tumor encasing the aorta and/or vena cava
• Tumor encasing the iliac vessels
• Pelvic tumor crossing the sciatic notch
Intraspinal tumor extension whatever the location provided that:
• More than one third of the spinal canal in the axial plane is invaded
and/or
• the perimedullary leptomeningeal spaces are not visible and/or
• the spinal cord signal is abnormal Infiltration of adjacent
organs/structures:
• Pericardium, diaphragm, kidney, liver, duodeno - pancreatic block, and
mesentery

29. Differentiating
neuroblastoma
Differentiating
neuroblastoma
at least 5% cells
less than 5% cells
Schwannian stroma richSchwannian stroma richGNB intermixed Differentiating neuroblasts
and mature ganglion cells
Differentiating neuroblasts
and mature ganglion cells
Maturing
According to the balance between neural-type cells (primitive
neuroblasts, maturing neuroblasts, and ganglion cells) and
Schwann-type cells (Schwannian-blasts and mature Schwann cells)
(NB), (GNB), and (GN).

30. Neuroblastoma
Neuroblasts at least 50%
of the tumor mass
Undifferentiated
neuroblastoma
Undifferentiated
neuroblastoma
Poorly differentiated
neuroblastoma
Poorly differentiated
neuroblastoma
Differentiating
neuroblastoma
Differentiating
neuroblastoma
at least 5% cells
less than 5% cells
All cells

31. Mature Schwannian stroma
and ganglion cells
Mature Schwannian stroma
and ganglion cells
Schwannian stroma -rich/
stroma –dominant /stroma
poor
Schwannian stroma -rich/
stroma –dominant /stroma
poor
GNB nodular
Ganglioneuroblastoma
>50% ganglioneuromatous,
a minor neuroblastomatous
Schwannian stroma richSchwannian stroma richGNB intermixed

32. Mature Schwannian stroma
and ganglion cells
Mature Schwannian stroma
and ganglion cells
GNB intermixed
GNB nodular
Differentiating neuroblasts
and mature ganglion cells
Differentiating neuroblasts
and mature ganglion cells
Maturing
Mature
Ganglioneuroma
Schwannian stroma
dominant

33. Shimada et al
• Age - linked classification
• Schwannian stroma - rich and stroma – poor
• FH and UH.
1984
The International Neuroblastoma Pathology Committee1994
•Ganglioneuroma (Schwannian stroma- dominant).
•Ganglioneuroblastoma, intermixed (Schwannian stroma- rich).
•Neuroblastoma (Schwannian stroma- poor).
•Ganglioneuroblastoma, nodular (Schwannian stroma- rich/
stroma- dominant and stroma- poor).

34. 18- 60 Months
•GNB- intermixed,
•Ganglioneuroma GNB - nodularNeuroblastoma
Pathology
> 5 years< 18 Months
Differentiating + low MKI Poorly differentiated and
or intermediate MKI
Degree of differentiation
Age
Neuroblastoma
• Age >5 Years
• Undifferentiated
• High MKI

35. Tumor cell ploidy
MYCN amplification
• A hyperdiploid 55% and 45%
of are diploid.
• The prognostic significance:
 <18 months,
Metastatic disease,
MYCN NA
• The oncogene MYCN is located
on chromosome 2p at 2p 23 – 24.
• MYCN amplification is an
intrinsic biological property.
• It is present at the time of initial
diagnosis and this feature does
not change with time.

36. 1p deletion
11q loss
17q gain
•Allelic loss of 1p occurs in about a third of
neuroblastoma patients.
•LOH of 1p was predictive of local recurrences
in low stage disease.
•25% of patients
•11q aberrations are often not associated with
MYCN amplification and are associated with
reduced progression free survival.
•11q strongly correlated with increase incidence
of relapse particularly metastatic relapses.
Having an extra part of chromosome 17 (17q gain) is also linked with
a worse prognosis. This probably means that there is an oncogene in
this part of chromosome 17, whereas whole chromosome 17 gain was
associated with good Prognosis {Van Roy et al., 2009}.

37. Anaplastic lymphoma kinase ( ALK )
•A predisposition gene for familial neuroblastoma.
•It can be used as target therapy.

38. •COG uses age, MYCN status, stage, histology, and DNA ploidy.
•SIOPEN uses age, MYCNstatus, and surgical risk factors defined
by imaging for assigning risk - group for locoregional tumors.
Prognostic factors
• Stage.
• Age ( < 18 months versus ≥ 18 months (547 days)).
• Histological category (ganglioneuroma, ganglioneuroblastoma–
intermixed).
• Grade of tumor differentiation (differentiating versus
undifferentiated or poorly differentiated).
• MYCN status.
• Presence/absence of 11q aberration.
• Ploidy ( ≤ 1.0 versus > 1.0).

39. Risk INSS Stage Age MYCN Status INPC Classification DNA Ploidy
Low 1 Any Any Any Any
Low 2A/2Bc
Any
Non amplified
Any Any
High 2A/2B Any Amplified Any Any
Intermediate 3 <547 d Non amplified Any Any
Intermediate 3 ≥547 d Non amplified Favorable Any
High 3 Any Amplified Any Any
High 3 ≥547 d Non amplified Unfavorable Any
High 4 <365 d Amplified Any Any
Intermediate 4 <365 d Non amplified Any Any
High 4 ≥365- <547 d Amplified Any Any
High 4 ≥365- <547 d Non amplified Unfavorable Any
High 4 ≥365- <547 d Non amplified Any =1
Intermediate 4 ≥365- <547 d Non amplified Favorable >1
High 4 ≥547d Any Any Any
Low 4S <365 d Non amplified Favorable >1
Intermediate 4S <365 d Non amplified Any =1
Intermediate 4S <365 d Non amplified Unfavorable Any
High 4S <365 d Amplified Any Any

40. II IVIII
Stage
FH UH
> 18 Months< 18 Months
Histology
Age
LR
IR
IR HR
HR
IR HR
IR HR
• Stage I---- LR
• NMYC A----HR

41. II IVIII
StageLR
IR HR
HR
12-18 Months
< 12 Months
Age
IR
FH+DNA I>1 UH or DNA I=1
Histology+ DNA I
IR HR
>18 Months
HR
IR HR
• Stage I---- LR
• NMYC A----HR

42. NMYC AFH + DNA I >1 UH or DNA I<1
Stage IV S
IR HRLR

43. • Principles of therapy
• Risk adapted therapy
• Recurrent neuroblastoma

44. Different treatment modalities like surgery,
chemotherapy and radiation therapy.
Role of surgery
•It can be used both in diagnosis and treatment.
•The primary treatment for low-risk tumors.
•Resectability is determined by tumor location and
mobility, relationship to major nerves and blood
vessels, the presence of distant metastases, and
patient age.

45. Role of surgery
For children with localized disease, without MYCN
amplification, gross surgical excision is considered
the main requirement for cure. {De Bernardi et al., 2008}
•Localized but unresectable NB carries a poorer
prognosis except in
 Infants or {Rubie et al., 2011}
Children with favorable biological features.
{Cohn et al., 2009}

46. Chemotherapy:
•Indications: neoadjuvant or adjuvant
•Low-risk disease: multi-agent low or moderate intensity
chemotherapy is reserved for those whose
Tumors cannot be resected
 Who have threatening symptoms of spinal cord
compression or respiratory or bowel compromise.
•Intermediate-risk disease: Moderately intensive multi agents
chemotherapy is applied before attempted resection.
•High-risk disease: intensive chemotherapy with a combination
of agents is used to shrink primary and metastatic tumors.

47. Radiation therapy:
•Indications
•LR NB patients:
It is reserved for unresectable tumors or
Progressive tumors unresponsive to chemotherapy or
Life threatening complications, neurologic compromise, or
tumor-related organ dysfunction unresponsive to
emergency chemotherapy.
• Intermediate-risk: Currently, cooperative groups withhold RT
for patients with, and recommend it only in the setting of
disease progression despite surgery and chemotherapy.
{Brodeur et al., 2011}
• High risk:

48. Low Risk NB:
•Observation
•Surgery
•Chemotherapy
•Radiation therapy
•Some newborns with small adrenal masses.
•Some infants with localized NB.
•Asymptomatic stage 4S disease. {Nuchtern et al., 2012}
• Surgery alone is the primary treatment for low-risk tumors.
{De Bernardi et al., 2008}
• It should be delayed when <50 % of the tumor can be safely
removed and neoadjuvant chemotherapy should be
administered prior to surgery.
• low or moderate intensity
 Those whose tumors cannot be resected
 Who have threatening symptoms of spinal cord
compression or respiratory or bowel compromise.
 Unresectable tumors or
 Progressive tumors unresponsive to chemotherapy or
 For those with life threatening complications, neurologic
compromise, or tumor-related organ dysfunction
unresponsive to emergency chemotherapy.

49. IntermediateRiskNB:
•SURGERY
•Chemotherapy
•Radiation therapy  The ultimate extent of surgical resection necessary for
optimal outcomes has not yet been determined.
{Baker et al., 2010}
 Moderately intensive multi agents chemotherapy
 In a COG trial for intermediate risk NB,
 Four cycles of chemotherapy were given for tumors
with favorable biologic features
 Eight cycles were given for tumors with unfavorable
features
 It is recommend it only in the setting of
disease progression despite surgery and
chemotherapy {Brodeur et al., 2011}.

50. High Risk NB:
1.Induction
2.Local Control
Intensive chemotherapy with a combination of
agents (e.g., platinum agents,
cyclophosphamide, doxorubicin, etoposide) is
used to shrink primary and metastatic tumors.
• Local control of the primary tumor is achieved with
surgical resection and radiation therapy.
• The importance of achieving a gross total resection of
the primary tumor in patients with disseminated disease
is controversial, with some studies {Zwaveling et al.,
2012},
• But not others suggesting a better outcome for
complete resection {Simon et al., 2013}.
• Radiotherapy dosed to the primary tumor bed and other
sites of bulky disease may be beneficial in preventing
local tumor recurrence {Haas-Kogan., 2003}

51. High RiskNB:
3.Consolidation
4.Maintenance
The consolidation phase includes higher dose
chemotherapy {melphalan and busulfan} followed
by autologous hematopoietic stem cell rescue
{Laprie et al., 2004}.
• Aim: eradication of minimal residual disease.
• The backbone: 13-cis-retinoic acid (RA) .
• Retinoids ---are substances that are similar to
vitamin A.
• Benefit
to help some cells mature into normal cells.
A COG study it improved their survival and
lowered their risk of recurrence.
• Time---after completion of consolidation therapy
to HR NB patients.

52. High RiskNB:
5.Novel therapies
• Additional immunotherapy: anti-GD2 antibodies was also found to have benefit
over (RA) alone for prevention of recurrence in a randomized trial {Yu AL et al.,
2010}.
• The immunotherapy approach resulted in a statistically significant improvement
in the two-year EF and OS rates (66 versus 46 %, and 86 versus 75 %,
respectively).
• Immunotherapies: anti-GD2 antibodies. {Shusterman et al., 2010}
• Targeted autologous T-cells. {Louis et al.; 2011}
• Neuroblastoma vaccines.
• Targeted therapy with drugs that act through known genetic mutations (e.g.,
ALK) or induce apoptosis (e.g., fenretinide).
{La Madrid et al., 2012}
• Modifiers of the tumor microenvironment such as antiangiogenic agents or
bisphosphonates. {Russell et al., 2011}
• Iodine-131-metaiodobenzylguanidine (MIBG), in conjunction with autologous
peripheral blood stem cell rescue. {Matthay et al., 2007}

53. • Tumor growth due to maturation should be differentiated
from tumor progression by performing a biopsy and
reviewing histology.
• Patients may have persistent maturing disease with
(MIBG) uptake that does not affect outcome, particularly in
patients with LR and IR disease {Marachelian et al., 2012}.
• When NB recurs in a child originally diagnosed with high-
risk disease, the prognosis is usually poor despite
additional intensive therapy {London et al.; 2011}.

54.  Prognostic factors determined at diagnosis for post relapse
survival include the following {London et al., 2011}:
– Age.
– INSS stage.
– MYCN status.
– Time from diagnosis to first relapse.
– LDH level, ploidy, and histologic grade of tumor
differentiation (to a lesser extent).
Among those older than 18 months, differentiating tumors did
much better than undifferentiated and poorly differentiated tumors.
Stages 1 and 2 have a better prognosis than stages 3 and 4
Hyperdiploidy had a better prognosis than patients with
diploidy

55. Low Risk
Locoregional
favorable biology
unfavorable biology
Surgery if not for chemotherapy
>90% <90%
Observation Chemotherapy
Surgery
Age
< 1 Y >1 Y
Aggressive
combination
chemotherapy
>90%
Observation
<90%
Chemotherapy

56. Low Risk
Metastatic
Age
< 1 Y >1 Y
•completely favorable,
• 4S pattern,
• the recurrence or progression
is within 3 months of diagnosis.
• Not 4S pattern or
• the recurrence or
progression is >3 months
of diagnosis.
Observation Chemotherapy
Aggressive
combination
chemotherapy

57. Intermediate Risk
Locoregional
> 3 M
Metastatic
Surgery
>90% <90%
Observation Chemotherapy
like patients with
newly diagnosed
HR NB

58. HighRisk
Any recurrence in patients initially classified as high
risk signifies a very poor prognosis {London et al.,
2011}.
Clinical trials may be considered.
Palliative care should be considered as part of the
patient's treatment plan.

59. HighRisk
1.Chemotherapy
•Topotecan in combination with cyclophosphamide or
etoposide {London et al., 2010} [Level of evidence: 1A].
•Temozolomide with irinotecan {Bagatell et al., 2011} [Level
of evidence: 2A].
•High-dose carboplatin, irinotecan, and/or temozolomide has
been used in patients resistant or refractory to regimens
containing topotecan {Kushner et al., 2010}.

60. HighRisk
2.Iodine 131-MIBG (131
I-mIBG)
For children with recurrent or refractory NB, 131
I-mIBG is an
effective palliative agent and may be considered alone or in
combination with chemotherapy (with stem cell rescue) in a
clinical research trial {French et al., 2013} [Level of
evidence: 3iiiA].

61. HighRisk
3.Second autologous stem cell transplantation (SCT)
For children with recurrent or refractory NB, 131
I-mIBG is an
effective palliative agent and may be considered alone or in
combination with chemotherapy (with stem cell rescue) in a
clinical research trial {French et al., 2013} [Level of
evidence: 3iiiA].
•In the setting of a clinical trial.
•German high-risk NB trials described 253 children relapsing after
intensive chemotherapy with autologous SCT who had a 5-year OS rate of
less than 10%. Only 23 of the 253 patients eventually proceeded to a
second autologous SCT following retrieval chemotherapy {Simon et al.,
2011} [Level of evidence: 3iiiA].
•Among these patients, the 3-year OS rate was 43%, but the 5-year OS
rate was less than 20%.
•Only a small minority of relapsed high-risk NB patients may benefit.