How is it treated & managed?
Phases of chemotherapy treatment
Ongoing treatment after induction chemotherapy
Overview
Symptoms of ALL 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. Children will have treatment planned depending on how responsive the leukaemia is likely to be to therapy and the risk of it coming back (relapse). Important parameters in this assessment are the age of the child, the white cell count at diagnosis and the chromosomal (cytogenetic) abnormalities in the leukaemic cells. Later modification of treatment depends on minimal residual disease (MRD) results and response to therapy within the first one to two weeks. Those children in the lowest risk group at diagnosis will be started on the least intensive protocol (regimen A in UK ALL2003). This group includes children aged 1-9 with a white cell count <50x109/l with no adverse cytogenetics. Children in the intermediate risk group will be started on a more intensive protocol (regimen B in UK ALL2003). These include children aged ≥ 1 year with white cells counts ≥50x109/l and all children aged ≥ 10 years regardless of their white cell count but with no adverse cytogenetics. Some children will be in a group where the prognosis is known to be poor. This is often determined by the cytogenetics of the leukaemic cells but will include children who do not go into complete remission at the end of induction therapy. These form a high risk group and will be given the most intensive protocol (regimen C in UK ALL2003). A small proportion of these children will require a stem cell transplant. Therapy can be intensified after induction if the MRD results are positive. Children aged under 1 year require different therapy from older children and are treated on an infant protocol which is more intensive. They have a significantly worse prognosis. 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
All children with ALL will have a diagnostic lumbar puncture to see if leukaemic cells are present in the spinal fluid surrounding the brain. All children receive treatment into the spinal fluid whether abnormal cells are present or not. Such treatment takes place at regular intervals during treatment of ALL and is called CNS (central nervous system) directed therapy. Leukaemic cells can hide out in the central nervous system during standard intravenous chemotherapy treatment and cause recurrent disease at a later date. It is this therapy and its effects on the brain and spinal cord that cause some of the most significant and enduring side effects of leukaemia treatment. If leukaemia cells are found in the spinal fluid, then high dose intravenous methotrexate or radiotherapy treatment is given to the brain. This causes significant additional short term and long term effects.
Phases of chemotherapy treatment
The initial diagnosis and treatment, including chemotherapy treatment, is likely to be given as an in-patient in hospital, along with supportive care. After the first cycle of chemotherapy the leukaemia will be undetectable when bone marrow slides are viewed down the microscope in >97% of children. This first cycle of chemotherapy to induce remission is often called ‘induction’ or ‘remission induction’ chemotherapy. Further treatment is then given predominantly as an out-patient. This will usually be in two phases -:
- ‘Consolidation’ or ‘intensification’ – a high dose treatment to stop the leukaemia coming straight back. CNS directed therapy is given during this phase.
- ‘Maintenance’ or ‘continuation’ - a long course of drugs which have a less intensive effect on the bone marrow to ensure the leukaemia does not relapse. CNS-directed therapy is given during this phase.
During the first admission to hospital for diagnosis and treatment an assessment of how the leukaemia has responded to therapy will be made. This is done morphologically i.e. looking down a microscope to determine ‘blast percentage’ on bone marrow aspirates 7 or 14 days after induction chemotherapy and using ‘minimal residual disease’ determination at the end of induction, day 28. These results are used to plan ongoing therapy which can be expected to last for 2 years for girls and 3 years for boys (in UK ALL 2003) for those children having chemotherapy as their main treatment. Some children will progress straight to bone marrow transplant or Peripheral Blood Stem Cell Transplant from a matched donor after their initial chemotherapy treatment. All these children will come from the high risk group.
Induction chemotherapy
Children will normally receive at least 3 separate drugs as part of their induction therapy. These are likely to be -:
- Vincristine (intravenous)
- Prednisolone/dexamethasone (steroid drug) (oral)
- L-asparaginase (intramuscular)
Children on the more intensive protocols (schedules B or C in UK ALL2003) will also receive -:
- daunorubicin (intravenous infusion).
The first part of induction chemotherapy is likely to be given in hospital. Additional therapy to the CNS will also be given. Usually -:
- Intrathecal methotrexate
Combination drugs are sometimes given:
- Intrathecal methotrexate with cytarabine and hydrocortisone
5-20% of children with ALL will have cranial irradiation - radiotherapy treatment to the head. This treatment has significant acute and long term side effects.
Ongoing treatment after induction chemotherapy
97% of children given induction chemotherapy will go in to remission within the first 4 weeks of treatment and move on to either -:
- consolidation chemotherapy including CNS-directed therapy followed by maintenance chemotherapy
- PBSCT or bone marrow transplant – less than 3 % of children. No further treatment is given after a transplant unless the patient relapses.
For more information see -:
Peripheral Blood Stem Cell Transplant (PBSCT) or Bone Marrow Transplant
Consolidation chemotherapy
Consolidation chemotherapy treatment is given over 6-10 months and begins once remission is achieved. Consolidation therapy is variable between children depending on treatment required but will normally consist of -:
- A block or blocks of therapy which may include -:
- intravenous chemotherapy
- intrathecal chemotherapy
- oral chemotherapy
- intramuscular therapy
Intensity and number of blocks will depend on response to therapy assessed at end of induction. Children with CNS disease will receive cranial irradiation or if under the age of 2 years enhanced intrathecal therapy. Boys with testicular involvement will receive testicular irradiation.
Children will be treated predominantly as outpatients or on a day case basis during this phase. They may be attending for chemotherapy from daily to weekly during this period and may also attend for monitoring and management of side effects of chemotherapy such as immunosuppression and bone marrow suppression. Admission is frequently needed for treatment of febrile episodes, infection or blood product support.
Maintenance chemotherapy
Most children will receive chemotherapy agents such as -:
- Daily oral Mercaptopurine
- Weekly oral Methotrexate
- Monthly intravenous vincristine and pulses of oral steroids (dexamethasone or prednisolone)
- Intrathecal chemotherapy with methotrexate every 12 weeks. Those who have had cranial irradiation receive no further intrathecal therapy
