How is it treated & managed?
Phases of chemotherapy treatment
Overview
Symptoms of AML develop quickly; a child is likely to become very ill with symptoms of their leukaemia over a few days or weeks although some children can appear deceptively well. All children will undergo assessment of their leukaemia as part of treatment planning and a course of induction chemotherapy treatment. Having completed induction chemotherapy there are three treatment options for children with AML -:
- The majority of children will have induction chemotherapy followed by 3 courses of consolidation chemotherapy over a period of approximately 6 months. The total treatment and recovery period lasts up to 1 year or so.
- A small number of children will have induction therapy followed by one course of consolidation therapy and then a bone marrow or peripheral blood stem cell transplant, very rarely a cord blood transplant, from a matched related or unrelated donor. Total period of treatment and recovery is 1 to 2 years.
- Children with a specific form of AML called ‘Acute Promyelocytic Leukaemia (APML)’ will undergo induction chemotherapy followed by consolidation therapy followed by lower dose maintenance chemotherapy. Children in this group will undergo a prolonged period of treatment similar to children with ALL. Total period of treatment and recovery is 3 to 4 years.
Most children will be treated in clinical trials. In a clinical trial current best treatment is usually compared to a new treatment that may be more effective at controlling the disease or less toxic in terms of acute or long term side effects. Being in a clinical trial has no effect on the care and mobility needs.
CNS directed therapy
Children will have a lumbar puncture (LP) at diagnosis to see if they have central nervous system (CNS) disease. If the lumbar puncture is clear, then two treatments (intrathecal therapy) with 3 drugs are given via further LPs, one after each of the first two courses of chemotherapy, to prevent development of disease as leukaemic cells can hide out in the central nervous system during standard intravenous chemotherapy treatment and cause disease later.
Those who have CNS disease will have a minimum of 6 triple drug intrathecal treatments in the first 3 weeks. Monthly intrathecal therapy is then given until after the final course of chemotherapy is completed. Only children who fail to clear disease with intrathecal therapy are considered for cranial radiotherapy; this therapy results in some of the most significant and enduring side effects of leukaemia treatment. Children who have received both cranial irradiation and intrathecal chemotherapy at the youngest ages are likely to have the severest and most enduring side effects.
Phases of chemotherapy treatment
The initial diagnosis and subsequent treatment is given as an in-patient in hospital, along with supportive care. The first phase of chemotherapy to induce remission is often called ‘induction’ or ‘remission induction’ chemotherapy. In the current UK trial for AML (excluding APML), a risk assessment takes place after the first course of therapy and further therapy then depends on the results. Both morphological response (blast count in bone marrow) and molecular response (Minimal Residual Disease) may be assessed. Specific biological markers may also be sought and appropriate targeted (biological) therapy added where indicated. Overall, the next phase of treatment will be some combination of three further courses of chemotherapy unless the patient is in the high risk category when a single course of therapy followed by stem cell transplant is considered.
A small group of children with promyelocytic acute myeloid leukaemia (APML) will not have a stem cell transplant but will have a further prolonged course of ‘maintenance’ or ‘continuation’ chemotherapy - a long course of lower dose drugs to ensure leukaemia remains in remission after consolidation treatment after initial remission induction.
Induction chemotherapy
Children will normally receive a combination of drugs as part of their induction therapy; these will often be given daily over 10 days. The combination of drugs used is likely to include some of the following -:
- Cytarabine*
- Daunorubicin* or idarubicin
- prednisolone/dexamethasone (steroid drug)
- thioguanine
- etoposide*
- Gemtuzumab* (biological therapy)
- al-transretinoic acid (ATRA) for children with promyelocyctic leukaemia only
- arsenic trioxide for children with promyelocyctic leukaemia only (blood monitoring required)
* Currently used in the UK AML 17 trial.
Induction chemotherapy is given in hospital as an intravenous infusion. Additional therapy to the CNS, usually intrathecal chemotherapy, will also be given as described above and will usually include -:
- Intrathecal methotrexate with cytarabine and hydrocortisone
The time from the start of a cycle of treatment to recovery is about 35 days. There may be as few as 6 days after recovery from one treatment cycle before the next is given. Around 90% of children given induction chemotherapy will go in to remission.
Consolidation chemotherapy
All children will progress to consolidation chemotherapy treatment after going in to remission. This is likely to consist of at least 3 further courses of intensive chemotherapy using the same or similar drugs to those used during induction with or without biological therapies. Drugs used will depend on type of leukaemia, response to induction therapy and the results of biological markers. The gaps between courses are usually no longer than 7 days.
Maintenance chemotherapy
Maintenance chemotherapy is ongoing chemotherapy used for a prolonged period following successful consolidation chemotherapy. It is only used for children with Acute Promyelocytic Leukaemia. Most children will take oral chemotherapy agents such as -:
- ATRA
- Mercaptopurine (oral drug taken every day)
- Methotrexate (oral drug taken once a week)
Some children may continue to receive intrathecal chemotherapy with methotrexate during this period.
Treatment for recurrent AML
AML may recur anytime after achievement of complete remission. It is most common for recurrence to occur in the first year after treatment (50 to 60%). Treatment of recurrence is again chemotherapy and possibly bone marrow transplant or Peripheral Blood Stem Cell Transplant (PBSCT). Survival is significantly reduced in children that have recurrent AML.
Peripheral Blood Stem Cell Transplant (PBSCT) or Bone Marrow transplant
