Childhood ALL treatment
How is ALL treated in children?
ALL usually progresses quite quickly so treatment needs to begin as soon as it is diagnosed. Children diagnosed with ALL need to be treated in a specialist paediatric referral centre under the care of a specialist doctor called a paediatric haematologist/oncologist.
The type of treatment protocol your child receives will depend on the ‘risk group’ they belong to. The risk group to which they belong will be defined based on a number of clinical and laboratory factors, both at diagnosis and during treatment, that predict the outcomes of particular treatment approaches. Sometimes adjustments need to be made to your child’s protocol depending on how well they are responding to treatment.
It is important to realise that whatever protocol your child follows, it is the best treatment known against ALL at this time.
Many chemotherapy drugs are also called cytotoxics (cell toxic) because they kill cells, especially ones that multiply quickly like cancer cells.
Chemotherapy is the main form of treatment given for ALL. The dose, timing and types of the drugs used will vary depending on the particular disease involved, your child’s age and general health, and the treatment protocol they are following. Chemotherapy is usually given as a combination of drugs (combination chemotherapy). These drugs act together and in different ways to destroy the leukaemic cells. Chemotherapy is usually given in several cycles (or courses) with rest periods in between. This is to allow your child’s body (the bone marrow in particular) time to recover from the side effects.
Some drugs are given in tablet or liquid form (orally), while others may be injected into a vein (intravenously or IV), into a muscle (intramuscularly or IM), and under the skin (subcutaneously or SC). Chemotherapy is also given intrathecally (into the spinal fluid) through a lumbar puncture, to either treat or prevent the spread of leukaemic cells into the central nervous system (CNS – the brain and spinal cord).
Intravenous drugs are usually given through a special line called a central venous catheter (central line or portacath). After their initial treatment your child may be able to receive a majority of their remaining treatment in the outpatient’s department of the hospital or clinic, or at home.
These drugs play an important role in the management of leukaemia. These drugs work by directly killing leukaemic cells as well as enhancing the effects of chemotherapy.
Central nervous system treatment and prophylaxis
Leukaemic cells are sometimes found in the central nervous system (brain and spinal cord) at the time of diagnosis. In other cases ALL reappears or relapses within this area at a later stage. Because the blood supply to the CNS is different from the blood supply to other parts of the body, this area can act as a ‘sanctuary site’ or hiding spot for leukaemic cells.
CNS treatment and prophylaxis (protection) will be given at various stages throughout your child’s treatment. This usually involves injections of chemotherapy drugs directly into the spinal fluid (intrathecal injection) through a lumbar puncture under anaesthetic. Some types of intravenous chemotherapy and cortico-steroid therapy also provide valuable protection for the CNS. On rare occasions, radiation therapy to the head (cranial irradiation) is also used.
The testes in boys can also act as a ‘sanctuary site’ for leukaemic cells. However, unless disease is found here at diagnosis no additional treatment is required. Your child’s haematologist/oncologist will decide on the most appropriate treatment in the event of testicular disease. This may or may not include radiotherapy. High dose chemotherapy may also be used.
What are the treatment phases for childhood ALL?
Treatment for ALL can be divided into three phases:
- remission induction therapy
- consolidation therapy (intensification)
- maintenance therapy.
Depending on the protocol your child is following, remission induction, consolidation, interim maintenance and intensification phases of treatment can last for up to 10 months.
Remission induction therapy
The goal of remission induction therapy is to destroy any detectable leukaemic cells in your child’s blood and bone marrow and allow their bone marrow to function normally again. Your child will need to be admitted to hospital for this first phase of treatment. Commonly used drugs in this phase of treatment include cortico-steroids, a combination of chemotherapy drugs and intrathecal chemotherapy .
While your child is having induction therapy they may also be given a drug called allopurinol. This is not a chemotherapy drug. It is used to help prevent a build-up of breakdown products of the destroyed leukaemic cells and to help the kidneys excrete these products safely.
Almost all children with ALL will achieve a remission following induction therapy. In a small number of cases however, the disease does not respond to treatment as expected and the child may be said to have resistant or refractory disease. In these cases the doctor may recommend a more intensive form of therapy to treat your child’s disease more effectively.
Soon after remission induction therapy finishes, consolidation therapy treatment is required to help destroy any leukaemia cells that may be left. This is important because it helps to prevent the disease from re-appearing (relapsing) or spreading to the central nervous system in the future. The consolidation protocol chosen for your child will depend on their estimated risk of relapse in the future. While the outlook for most children with ALL is very good, certain factors (known as prognostic factors) give some children a better chance of being cured of their disease with treatment than others.
The most important of these factors is how well your child’s disease responds to initial treatment, or in other words, how quickly they achieve a remission and how much disease is left over in their body after this initial treatment.
Children are categorised as having low, standard or high-risk ALL. This ensures that the most appropriate and effective ‘risk-based’ therapy can be chosen for every child. Children with high-risk disease can have as good a chance of being cured as those with lower-risk disease when they receive appropriate treatment.
Consolidation therapy usually involves ‘blocks’ of intensification treatment over several months and includes the use of additional chemotherapy drugs. This is given to reduce left over disease to a minimum (minimum residual disease).
Maintenance therapy is designed to help keep your child’s disease in remission and prevent it from reappearing (relapsing) in the future. Common maintenance protocols involve chemotherapy tablets taken daily as well as in some protocols, injections of chemotherapy with courses of cortico-steroids given monthly. In addition, intrathecal injections of chemotherapy may be given periodically to prevent disease relapsing in the central nervous system. This phase of treatment will continue until the treatment is completed.
Currently, the total treatment time for children with ALL is just over two years for girls and just over three years for boys. During this time your child will be treated as an outpatient providing they are well. Your doctor will advise you when it is safe for your child to return to normal daily activities like school, and when it is safe to continue immunisations, which are usually delayed for six to nine months after your child has finished treatment.
While your child is receiving maintenance therapy the doctor will make an assessment of how well your child is progressing and adjust their treatment as necessary.
For a small number of children, the chance of curing ALL with chemotherapy alone may be low. If these children have a sibling with a similar tissue type, or if a suitable unrelated donor can be found on the international registries, the doctors may recommend chemotherapy followed by a haematopoietic stem cell transplant. This uses very high doses of chemotherapy and/or radiotherapy as part of the stem cell transplant procedure.
Due to the complex side effects associated with this form of treatment and the success of current chemotherapy protocols used to treat ALL, a transplant is usually only necessary in selected cases where it has been shown to give a better chance of cure than chemotherapy alone. An example of this might be in the case of very high-risk disease, relapsed disease, or disease which is proving resistant to conventional treatment.
Finding out that your child’s leukaemia has relapsed can be devastating, but there are often ways of getting it back under control. The treatment of relapsed disease depends on a number of factors including the duration of the remission and the site at which the disease has reappeared.
Other factors are also considered including your child’s age and the genetic makeup of the relapsed leukaemic cells. Similar drugs to those used to initially treat leukaemia, different drugs, and in some cases, high dose chemotherapy and a stem cell transplant may be used to treat relapsed disease. Late relapse (relapse that occurs years later) will often respond well to another course of chemotherapy whereas early relapse is generally best treated using stem cell transplantation.