Childhood Cancer

The changing landscape of childhood ALL

April 1, 2024 Word for Word Media 0Comment

Acute lymphoblastic leukaemia (ALL) remains a challenging and life-threatening disease. However, with new treatments and insights into the disease more children are being cured than ever before.

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What is ALL?

Acute lymphoblastic leukaemia is a cancer of the white blood cells that are produced in bone marrow (spongy central area of bone where all blood cells are made).

In ALL, the bone marrow makes excess abnormal immature lymphocytes. These cells grow out of control and enter the blood.

They’re unable to fight infections and may aggregate or gather in certain organs like the lymph nodes, liver, spleen, skin, testes, and brain.

In addition, the bone marrow becomes packed with these abnormal cells, leaving no space to produce normal red blood cells, platelets, and other white blood cells. This leads to the common symptoms of leukaemia: tiredness and pallor due to anaemia or low haemoglobin; bleeding; abnormal bruising due to low platelets; bone pain from the abnormal cancer cells that congregate in the bone marrow; and fever due to infection. Children may also present with enlarged lymph nodes, liver and spleen.

Most common cancer in children

ALL is the commonest cancer seen in children and accounts for nearly one third of cases. There are several types of ALL, with the most common being pre-B ALL and T-cell ALL. Overall survival for children with ALL has increased dramatically from the early 70s where most children died of the disease, to a cure rate of over 90% in first world countries. The goal of treatment is now to risk stratify patients into those whose treatment and thus side effects related to treatment are decreased without an increase in relapse, and those who need more intensified therapy. A small group of children don’t respond to therapy or relapse on or after therapy has been completed. These are the children who are the most difficult to treat.


Measurable residual disease (MRD) is one of the most important markers for prognosis and risk of relapse, with MRD testing becoming better and better.

Standard chemotherapy is still standard of care and most patients are treated with this. Steroid therapy is an important component of this. Treatment is divided into different phases, each with a different aim. Induction phase aims to reduce the number of leukaemic cells as quickly as possible. The consolidation phase intends to destroy any remaining leukaemic cells, before interim maintenance and then delayed intensification mop up any residual disease. Maintenance phase lasts approximately two years and prevents the disease from coming back. All children also require specialised therapy to prevent and treat any leukaemic cells that may be in the central nervous system. This is done by way of a lumbar puncture and the administration of chemotherapy into the spinal fluid. Radiation may also be required. Stem cell transplantation may also be needed in high-risk patients.

New advances in treatment

For these high-risk children, or those who don’t respond to therapy or relapse, major advances for both frontline and relapse treatment have been developed.

Tyrosine kinase inhibitors

The first advancement is tyrosine kinase inhibitors for treatment of Philadelphia positive ALL. Tyrosine kinases are enzymes that send messages to cancer cells telling them to grow and divide. Tyrosine kinase inhibitors block these signals at a gene level, and stop the cancer cells from growing, without disturbing the normal body cells that don’t have the genetic mutation. Although they can’t be used as monotherapy and must be added to a normal chemotherapy backbone, they have revolutionised treatment of certain ALL subtypes.


Immunotherapy uses the patient’s own immune system to kill the leukaemia cells.

Blinatumomab is a bispecific T-cell engaging antibody or BiTE cell. It directs the patient’s own T-cell to the CD19 positive leukaemia cell, activating the T-cell to fight and kill the leukaemic cell. These T-cells may persist in the patient’s bloodstream, allowing longer term killing of leukaemic cells.

Blinatumomab is currently available for use in SA and is administered as a 28-day continuous infusion, whichis usually started in hospital, but the patient may go home with a home pump once they’re stable. It unfortunately only works on leukaemic cells that express CD19 on their surface and is therefore not used in T-cell leukaemia. The most common side effects include cytokine release syndrome and some mild, mostly reversible neurological symptoms.

CAR T-cell therapy

CAR T-cell therapy is another breakthrough immunotherapy which has changed the face of ALL treatment. T-cells in the blood are good at fighting infections, but they may have trouble recognising leukaemic cells, allowing the leukaemia cell to hide away. In CAR T therapy, T-cells are removed from the patient and genetically modified in a laboratory to recognise and target a specific marker on the cancer cell. These changed T-cells are now called chimeric antigen receptor or CAR T-cells and they grow and multiply in the lab before they are re-introduced into the patient. The aim is for the CAR T-cell to recognise and attack any leukaemic cell in the body. The most common side effects include allergy, cytokine release syndrome, neurological effects, and an increased risk of infection. CAR T-cell therapy isn’t currently available in SA, but we are hopeful that it will be soon.

Dr Kate Bennett

MEET THE EXPERT – Dr Kate Bennett

Dr Kate Bennett is a paediatric oncologist; she qualified as a paediatrician in 2009 and then as a paediatric oncologist in 2011. She has a special interest in the treatment of paediatric leukaemia and lymphoma, immune thrombocytopaenia and sickle cell anaemia.

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