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SJD Barcelona Children´s Hospital

Passeig Sant Joan de Déu, 2, 08950 Esplugues de Llobregat

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Neuroblastoma (high and low risk)

Neuroblastoma is the most common tumour during the first 5 years of life. It is a heterogeneous group of tumours that can affect different body compartments.

Pathology description

The incidence of neuroblastoma is approximately one case per 70,000 live newborns, which in Spain amounts to some 100 cases a year. The disease behaves in many different ways: it can be benign and require no treatment (50%-60% of cases), or be aggressive, requiring multimodal treatment (45%-55%).

High-risk neuroblastoma, the type treated mainly at the á SJD Barcelona Children's Hospital, is difficult to treat and has a survival rate of 55% at the best centres. The treatment  of children with high-risk neuroblastoma is a complex process that calls for the involvement of numerous experts in fields such as molecular biology, molecular pathology, radiobiology, nuclear medicine, oncological surgery, oncological neurosurgery, radiation therapy and paediatric oncology. Few hospitals in the world have the necessary range of experience and technology to offer the best option to patients with high-risk neuroblastoma.

Precision molecular diagnosis

The Paediatric Oncology Laboratory team of SJD Barcelona Children's Hospital works with techniques that make it possible to ascertain what type of neuroblastoma each patient has thanks to molecular tumour testing. A precise diagnosis makes for a better prognosis, since it makes it possible to ascertain the lesion's degree of malignancy and to work with treatments specifically targeting each type of tumour, with personalised treatments.

Treatment

The treatment of high risk neuroblastoma continues to be one of the greatest challenges facing paediatric oncology professionals. The development of latest-generation anti-GD2 immunotherapy has yielded impossible-to-imagine long-term survival results in relapsing patients or in those with refractory disease.

Researchers from SJD Barcelona Children's Hospital and the Institut de Recerca Sant Joan de Déu have published the results of the treatment with the anti-GD2 humanised antibody naxitamab (DanyelzaⓇ) combined with the granulocyte-macrophage colony-stimulating factor (GM-CSF; LeukineⓇ) in patients with high-risk neuroblastoma in complete remission following induction treatment (with chemotherapy and surgery), demonstrating an overall survival rate of more than 90% in three years  without the need for high-dose chemotherapy or autologous transplantation.

Immunotherapy with anti-GD2 antibodies manages to “train” the patient's immune system to recognise and eliminate the neuroblastoma cells, which are major experts in evading the immune surveillance system.

Results according to the type of treatment

The SJD Barcelona Children's Hospital achieved a 90% overall survival rate after three years in patients with high-risk neuroblastoma in first complete remission after induction treatment and without the need for high-dose chemotherapy and autologous transplantation. The overall survival after 3 years in patients with high-risk neuroblastoma  in first or second complete remission treated with naxitamab and GM-CSF is 82.4%.

What can we offer for the treatment of high-risk neuroblastoma

Induction treatment (surgery and chemotherapy)

A surgery-only treatment is offered to patients with low-risk neuroblastoma. The overall survival rate of this group is 98% in the long term.

For high-risk patients, SJD Barcelona Children's Hospital has developed its own adaptation of the N7 protocol of the Memorial Sloan Kettering Center in New York (MSKCC), mN7 with early surgery as induction standard. Patients in complete remission after induction follow the consolidation protocol with radiation therapy and immunotherapy with naxitamab. The entire treatment takes 12 months. Patients in continuous first complete remission have an estimated overall survival rate of above 90% after 3 years.

Immunotherapy with naxitamab

SJD Barcelona Children's Hospital is one of the few centres that currently offers anti-GD2 immunotherapy with the Hu3F8 antibody (naxitamab). Naxitamab (DanyelzaⓇ, USA) is FDA-approved (Food and Drug Administration) for patients with high-risk neuroblastoma with refractory or relapsing disease exclusively in the osteomedullary compartment (bone marrow and/or bone).

More information
Combined treatment (HITS)

The combined treatment called HITS is the first chemo-immunotherapy regimen given simultaneously and developed initially at the Memorial Sloan Kettering Cancer Center and given at our centre since 2018. Experience with HITS shows that complete remission is achieved in 40% of patients.

The current chemo-immunotherapy protocol developed at our centre, NICE, includes HITS cycles and NICE (naxitamab + ICE chemotherapy) cycles. The NICE protocol is indicated in patients with a very poor prognosis with neuroblastoma resistant to treatment with naxitamab or with surgically unresectable refractory disease of the soft tissues.

Omburtamab 101

The increase in the survival rate of patients with high-risk neuroblastoma thanks to the new treatments has led to an increase in central nervous system (SNC) relapses. Our centre offers rescue treatment with radioimmunotherapy with the 8H9 monoclonal antibody (Omburtamab) within the YmAbs 101 clinical trial. The MSKCC's experience demonstrates that up to 50% of patients with SNC relapse treated with regimens including Omburtamab can recover.

Indicators

90
%

Induction treatment without relapse after the first complete remission

82.4
%

Treatment with naxitamab and GM-CSF in first or second complete remission

Overall survival rate at 3 years in high-risk NB

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