Treatments for childhood AML
The main treatment for childhood acute myelogenous leukemia (AML) is chemotherapy. Stem cell transplant may be done once the disease goes into remission. An important part of treatment is central nervous system (CNS) therapy, which is given to prevent or treat the spread of leukemia to the brain or spinal fluid. Radiation therapy may be used to treat AML in certain areas if it is causing serious problems.
Some children are very ill when they are diagnosed with AML. Others become ill during treatment. Low blood cell counts due to AML or its treatment can cause serious problems, such as infections, bleeding and even heart failure. Supportive therapy, such as antibiotics or blood transfusions, may be needed to treat or prevent some of these problems before and during treatment for AML.
Treatment plans are designed to meet the unique needs of each child with cancer. Doctors make treatment decisions for AML based on certain prognostic factors. These prognostic factors can be combined to give a level of risk.
This approach means that children with a very good prognosis are treated with less intensive and less toxic therapy. It also means that those with a less favourable prognosis will be given more intensive therapy to increase their chances of survival.
The prognostic factors used to design a treatment plan include:
- subtype of AML
- level of risk (high-risk AML needs more intensive treatment)
- leukemia that has spread to the CNS (children with leukemia cells, or blasts, in the spinal fluid at diagnosis need treatments directed to the CNS)
- chromosome and gene changes in the leukemia cells
- response to treatment (children whose leukemia responds more slowly to initial treatment need more aggressive treatment)
Many different protocols are used to treat childhood AML, but they generally follow a similar pattern. Treatment usually includes different phases of chemotherapy that use different combinations of drugs and schedules. Central nervous system (CNS) therapy is given during each phase.
Chemotherapy for AML usually includes the following phases.
The goal of induction chemotherapy for childhood AML is to bring about remission by killing all the leukemia cells, or blasts, in the blood, bone marrow and cerebrospinal fluid (CSF). It usually lasts 4–8 weeks and involves 2–3 cycles of combination chemotherapy. Children with Down syndrome who have FAB M7 AML do well with lower-dose chemotherapy regimens. The child may need to spend some or much of this time in hospital.
Bone marrow aspiration may be done during induction chemotherapy to find out if the leukemia is responding to treatment. Induction chemotherapy is repeated until there are no leukemia cells in the bone marrow.
The most common chemotherapy combinations used for AML include:
- cytarabine (Cytosar, Ara-C) and daunorubicin (Cerubidine, daunomycin)
- cytarabine, daunorubicin and etoposide (Vepesid, VP-16)
- daunorubicin, cytarabine and thioguanine (Lanvis, 6-TG)
Other drugs that may be used include:
- amsacrine (AMSA PD)
- thioguanine (Lanvis, 6-TG)
- mitoxantrone (Novantrone)
- idarubicin (Idamycin)
Consolidation, or intensification, chemotherapy is the second phase of treatment. Most children with AML receive consolidation chemotherapy after induction chemotherapy. The goal of consolidation therapy is to kill any leukemia cells, or blasts, that are still in the blood or bone marrow once complete remission has been reached. It helps prevent leukemia from coming back (recurring).
Consolidation chemotherapy usually includes very intense treatment for 4–6 months. The most common type of chemotherapy used is high-dose cytarabine combined with other chemotherapy drugs. The most common drug combinations used include:
- cytarabine and etoposide
- cytarabine and mitoxantrone
- cytarabine and asparaginase (Kidrolase), asparaginase erwinia (Erwinase) or pegaspargase (Oncaspar)
Other chemotherapy drugs that may be used along with cytarabine include:
- ifosfamide (Ifex)
- fludarabine (Fludara)
Children who have a high risk of relapsing or poorer prognostic factors and who have a brother or sister who is a good match are often treated with stem cell transplant once the leukemia is in remission. Children who have a low risk of relapsing or good prognostic factors don’t need a stem cell transplant unless the AML relapses, or recurs. Children with Down syndrome often don’t need stem cell transplant because they have a better prognosis and lower risk of recurrence.
Allogeneic stem cell transplant uses stem cells from a donor (usually a brother or sister). This type of transplant is the preferred treatment for children with AML who are at high risk of relapse or who have disease that is resistant to treatment. Several large clinical trials for children with AML have found that autologous stem cell transplant and intensive chemotherapy work equally well.
The central nervous system (CNS) is made up of the brain and spinal cord. CNS therapy is given during all phases of treatment for childhood AML. It helps prevent any leukemia cells, or blasts, from spreading to the CNS and kills any leukemia cells present in the CNS. This helps to keep the leukemia from recurring.
CNS therapy usually involves intrathecal chemotherapy, where the drugs are given directly into the cerebrospinal fluid (CSF). Intrathecal chemotherapy is usually given at the start of treatment for AML and every 1–2 months for as long as treatment lasts. Intrathecal chemotherapy may include methotrexate, cytarabine or both. Hydrocortisone may also be given.
In rare cases, radiation therapy may be given to the head (called cranial radiation therapy) as part of CNS therapy for AML. It is usually avoided if at all possible because radiation therapy to the brain can affect growth and development in young children.
Many children with leukemia enter a clinical trial that is tailored to their subtype and risk level of AML. The clinical trial protocol outlines the new combinations and doses of the chemotherapy drugs that are used.
For more information, go to clinical trials.
A decrease in or the disappearance of signs and symptoms of a disease (such as cancer).
Complete remission means the disappearance of all signs or symptoms. Partial remission means a decrease in or disappearance of some, but not all, signs and symptoms. Spontaneous remission is an unexpected improvement that occurs with little or no treatment.
Research at the Canadian Centre for Applied Research in Cancer Control led to a new standard in leukemia testing.
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