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The Potential Of Immunotherapy In Treating Paediatric Blood Cancer

As a blood and bone marrow cancer, childhood ALL remains the most prevalent paediatric cancer. ALL happens when stem cells that become lymphoblasts fail to mature into B or T lymphocytes. Also termed as leukaemia cells, these cells are unable to combat infection very well. As the cancerous cells keep growing in the child’s blood and bone marrow, the space for platelets and healthy red and white blood cells keeps decreasing, leading to decrease of all kinds of healthy blood cells, a condition called as pancytopenia. Consequently, it results in easy bleeding, anaemia and infection. If left untreated, ALL can swiftly get worse and can be fatal.

Over the decades, major improvements have been recorded as 90% of children survive five years or longer after the initial diagnosis. However, some subgroups fare poorly, especially those who relapse. The therapy burden is heavy for children which includes both short-term and long-term toxicities. Some subgroups of children with ALL don’t fare well and includes infants, adolescents, the youth and those with unfavourable genetic conditions.  The prognosis for kids with relapse is poor, marked generally with resistance to traditional therapeutic agents, unlike children with a newly diagnosed condition.

Due to the above challenges, novel, targeted therapy approaches are attracting more interest. With numerous new immunotherapeutic agents proving effective in refractory or relapsed disease, these are under investigation in leading treatment regimens.

Some Likely Causes and Potential Symptoms

Childhood ALL can occur when there are changes in the functioning of the blood stem cells, particularly in the way they grow and split into new cells, which is a result of the failure of the immune system. It is often difficult to decipher the specific triggers for these cell changes. Some likely genetic risk factors include Down syndrome, Bloom syndrome, Fanconi anaemia and specific changes in the genes or chromosomes. Additional risk factors include exposure to X-rays before birth, exposure to radiation and treatment with chemotherapy in the past.

Symptoms of childhood ALL appear when platelets and red blood cells are insufficient in number but white blood cells that do not function so well are too many. Parents must check with the paediatrician if their child displays symptoms such as easy bruising or bleeding, weakness or tiredness, petechiae (flat, pinpointed, dark-red spots below the skin due to bleeding), bone or joint pain, breathing trouble or shortness of breath, pain or feeling of fullness below the ribs, abdominal pain, loss of appetite and weight loss and unexplained fever. Although these symptoms may be due to other problems rather than ALL, the best way to check is to visit the doctor.

The Three Treatment Phases

Childhood ALL is treated in three phases:

  • Remission induction: This constitutes the first treatment phase where the objective is to eliminate leukaemia cells present in the blood and bone marrow. This drives the disease into remission.
  • Consolidation or intensification: This is the second treatment phase that begins after the leukaemia goes into remission. Consolidation or intensification therapy aims to eliminate any residual leukaemia cells in the body that could lead to a relapse.
  • Maintenance: Also referred to as the continuation therapy phase, this comprises the third treatment stage wherein any residual leukaemia cells are killed to stop them from re-growing and leading to a relapse. Unlike remission induction and consolidation or intensification phases, cancer treatment in this phase is usually administered in lower doses.

The Use of Immunotherapy

Immunotherapy deploys drugs to assist the children’s immune systems in detecting and destroying cancerous cells. Made by the body or in the lab, these substances are useful in boosting, directing or restoring a child’s natural defences against cancer. Immunotherapy examples for treating childhood leukaemia include blinatumomab and CAR T-cell therapy, among others.

A kind of targeted therapy drug termed a bispecific T-cell engager (BiTE), Blinatumomab brings healthy T cells – immune cells, that facilitate the destruction of cancerous cells – and leukaemia cells within close range so the T cells can kill the leukaemia more effectively. Blinatumomab does this by binding itself to the protein CD3 in healthy T cells and another protein called CD19 in B cells (cancerous immune cells in acute lymphoblastic leukaemia).

In the case of CAR (chimeric antigen receptor) T-cell therapy, the treatment changes the T-cells – a kind of immune system cell – of the patient, so they can attack specific proteins on the cancerous cells’ surface. This is done by taking T cells from the leukaemia patient and adding special receptors to their surface in the lab. Thereafter, the CAR T cells are infused in the child. After increasing in number in the child’s blood, the CAR T cells go about attacking and destroying the cancerous cells.  Currently, this therapy is under evaluation in treating childhood ALL that has relapsed a second time.

Understanding the Threat of Side Effects

As these therapies could have serious side effects, they must be administered only in a hospital with staff specially trained in such use. For example, the possible side effects of CAR T-cell therapy could include Cytokine Release Syndrome which is accompanied by fever, difficulty in breathing and low blood pressure; neurological problems like seizures, confusion and loss of consciousness; infections that manifest in the heightened risk of viral, bacterial and fungal infections.

Despite such side effects, given the life-threatening nature of childhood leukaemia or blood cancer, immunotherapy offers the best hope of extending the lifespan of affected children.