Neuroblastoma: the future of stem cell treatment for childhood cancers

by Wideacademy - 10 January, 2018

  • Cancer
  • Childhood cancer
  • Stem Cell Transplant
  • Peripheral Blood Stem Cells
  • Autologous
  • Chemotherapy

What is neuroblastoma?

Neuroblastoma is a cancer of immature nerve cells called neuroblasts, which grow into tumours.

It is the most common cancer in babies and the third most common cancer in children, mostly affecting under 5s.

Usually it starts in the adrenal glands just above the kidneys, but it can also develop in the neck, chest, abdomen or spine.

The cancer can spread through the blood and lymphatic system to the bone marrow, bones, lymph nodes, liver and skin.

Symptoms can include:

  • tiredness
  • loss of appetite
  • weakness
  • bone pain
  • numbness
  • bluish lumps under the skin
  • eyes that bulge
  • dark circles under eyes

It can be difficult to diagnose neuroblastoma because the symptoms are often easy to mistake for other common childhood ailments.

Some children who develop neuroblastoma will have none of the above symptoms.

Diagnosis is made via a biopsy. If diagnosed, the child’s cancer will be classified according to three levels of risk based on their age and the tumour’s development:

Low risk — when the tumour is only in one area, is unlikely to spread and can be removed by surgery

Intermediate risk — the tumour cannot be removed easily by surgery

High risk — an aggressive tumour that has spread to other parts of the body

Treatment for aggressive tumours is usually a combination of chemotherapy, surgery, stem cell transplantation, radiation and immunotherapy.

How can stem cells help?

Stem cells are part of the standard treatment process for high risk neuroblastoma.

Children are usually given high-dose chemotherapy to target their tumour, whilst blood-forming stem cells are taken from their own blood to be transplanted back into them, after the course of chemotherapy has finished. This is called an autologous haemopoietic stem cell infusion. It restores the bone marrow that has been destroyed and helps build up the immune system and blood count.

A child with neuroblastoma will have their own (autologous) peripheral blood stem cells (PBSCs) transplanted rather than stem cells from their bone marrow, or a transplant from a bone marrow donor (allogeneic).

There is a better rate of engrafting when PBSCs are used as transplants of donor stem cells have a higher likelihood of graft-versus-host disease (GvHD), which means that they are rejected by the child’s body. In an autologous transplant there is no risk of GVHD, because the stem cells are the child’s own — a perfect match.

However, there is a risk that some of the cells that are put back into the child’s body could still be cancerous.

Harvesting and storing autologous PBSCs means that children can be treated beyond the limits of what their bone marrow can tolerate, because it can be rebuilt afterwards. In this way, stem cells are a vital part of the treatment process and are used in clinical trials testing varying types and levels of chemotherapy — or other drugs — that could lead to breakthroughs in the treatment options available for this disease.

The Children’s Oncology Group (COG) has tested the safety and efficiency of the chemotherapy drugs busulfan and melphalan, followed by stem cell rescue in a clinical trial.

Another COG study suggests that busulfan and melphalan may cause fewer side effects and be more effective than carboplatin, etoposide and melphalan.

Children who received cycles of high-dose therapy alongside a stem cell transplant were seen to have an improved, event-free survival.

The future of stem cell treatments

Researchers are studying several methods for treating cancer with gene therapy.

One method involves inserting genes into healthy blood-forming stem cells to make them more resistant to the side effects of cancer treatments, such as high doses of anti cancer drugs.

However, there are other approaches that genetically engineer healthy cells to improve their ability to fight cancerous cells when replaced in the body.

One such current trial is looking at a new treatment using CAR-T (chimeric antigen receptor and T-cell therapy) therapy, specifically using anti-GD2 T-cells to fight neuroblastoma.

CAR-T uses the child’s own immune system to fight cancer, by adding an engineered gene, the ‘CAR’ to T cells. This leads the T-cells, which are part of the body’s immune system and taken from the blood, to recognise and attack specific cancer cells.

CRISPR/Cas 9 is a new technology that allows for more precise and effective gene editing. Combining it with CAR-T improves scientists’ capability to create powerful, specific and programmable T-cells that can be applied to different types of cancer.