Treatments for childhood ALL
The main treatment for childhood acute lymphoblastic leukemia (ALL) is long-term chemotherapy. An important part of this treatment is central nervous system (CNS) therapy, which is given to prevent or treat the spread of leukemia to the brain or spinal fluid. Treatment for childhood ALL usually takes 2–4 years.
Some children are very ill when they are diagnosed with ALL. Others become ill during treatment. Low blood cell counts due to ALL 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 ALL.
Treatment plans are designed to meet the unique needs of each child with cancer. Doctors make treatment decisions for ALL 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 or lower level of risk are treated with less intensive and less toxic therapy. It also means that children with a less favourable prognosis or higher level of risk will be given more intensive therapy to increase their chances of survival.
The prognosis factors used to design a treatment plan include:
- age of the child at diagnosis (children younger than 1 or older than 9 need more aggressive treatment)
- white blood cell (WBC) count at diagnosis (children with a WBC count higher than 50,000 cells/mm3, or 50.0 x 109 cells/L, need more aggressive treatment)
- subtype of ALL (mature B-cell ALL is often treated with more intense chemotherapy because it has a poorer prognosis)
- leukemia has spread to the CNS or testicles (children with leukemia cells, or blasts, in the spinal fluid or testicles at diagnosis need more aggressive treatment)
- chromosome 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 ALL, but they generally follow a similar pattern. Treatment usually includes different phases of chemotherapy. Central nervous system (CNS) therapy is given during each phase.
Chemotherapy for ALL usually includes the following phases.
The goal of induction chemotherapy for childhood ALL is to bring about remission by killing all the leukemia cells, or blasts, in the blood, bone marrow and cerebrospinal fluid (CSF). Induction chemotherapy lasts 4–6 weeks. The child may need to spend some or much of this time in hospital. Over 95% of children with ALL go into remission after 1 month of treatment.
Bone marrow aspiration and biopsy may be done during induction chemotherapy to find out how the leukemia is responding to treatment.
The drugs given during induction chemotherapy vary depending on the level of risk. The most common chemotherapy combination used for standard-risk or low-risk ALL includes:
- vincristine (Oncovin)
- asparaginase (Kidrolase), asparaginase erwinia (Erwinase) or pegaspargase (Oncaspar)
- dexamethasone (Decadron, Dexasone) or prednisone
For higher-risk ALL, one of the following drugs is added to the above combination:
- daunorubicin (Cerubidine, daunomycin)
- doxorubicin (Adriamycin)
Consolidation, or intensification, chemotherapy is the second phase of treatment. All children with ALL 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 recurrence in distant sites, such as the CNS or testicles.
Different drugs are given during consolidation chemotherapy than those used during the induction phase. The intensity and type of consolidation chemotherapy can vary depending on the level of risk. The consolidation phase lasts 4–6 weeks.
The most common chemotherapy drugs used during consolidation include:
- cyclophosphamide (Cytoxan, Procytox)
- cytarabine (Cytosar, Ara-C)
- mercaptopurine (Purinethol, 6-MP)
Other chemotherapy drugs that may be used during this phase include:
An interim maintenance phase usually follows consolidation chemotherapy. This phase is similar to a standard maintenance cycle. It allows the bone marrow to recover while maintaining remission. Interim maintenance may last 6–8 weeks.
Chemotherapy drugs used during interim maintenance may include:
- intermediate or high-dose methotrexate
- prednisone or dexamethasone
The delayed intensification, or re-induction, phase gives more intense chemotherapy before maintenance chemotherapy starts. It helps to prevent leukemia from recurring.
Delayed intensification is usually given 3–4 months after the child reaches remission from induction chemotherapy. It is given in blocks that usually last 8 weeks.
For some children at high risk, an extra block of delayed intensification chemotherapy may be given, depending on the child’s particular treatment plan. Delayed intensification chemotherapy may be followed by another block of interim maintenance chemotherapy.
The chemotherapy drugs used during delayed intensification may be the same as those used during the induction and consolidation phases. The exact timing of treatments and the drugs used are specific to each child’s leukemia.
Drugs that may be used during delayed intensification chemotherapy include:
- thioguanine (Lanvis, 6-TG)
Once the other treatment phases lower the number of leukemia cells, or blasts, maintenance chemotherapy begins. During this final phase, chemotherapy is given at a low level of intensity (lower doses given less frequently) over a longer period of time to maintain remission.
The maintenance phase usually lasts 2 years for girls and 3 years for boys. In general, maintenance chemotherapy is longer for boys because leukemia cells can spread to the testicles.
The maintenance chemotherapy phase is much less intensive than the other phases. It mainly involves taking oral (by mouth) medicine at home each day. Intermittent intravenous and intrathecal chemotherapy is also given during this phase. Intrathecal chemotherapy is given directly into the cerebrospinal fluid (CFS) by lumbar puncture. Children can usually take part in their normal daily activities as soon as they feel well enough and most children return to school during this phase.
Chemotherapy drugs used during the maintenance phase include:
- daily oral mercaptopurine
- weekly oral methotrexate
Intermittent doses or pulses of other chemotherapy drugs are often added, such as:
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 ALL. It helps prevent any leukemia cells, or blasts, from spreading to the CNS and kills any leukemia cells in the CNS. This helps to keep the leukemia from recurring.
The type of CNS therapy given will depend on the level of risk and whether or not there is evidence that the cancer has spread to the CNS at diagnosis. CNS therapy usually involves intrathecal chemotherapy, where the drugs are given directly into the cerebrospinal fluid (CSF). Intrathecal chemotherapy may be given alone or with systemic chemotherapy, radiation therapy or both.
Intrathecal chemotherapy is most commonly used for CNS therapy. It is usually started at the beginning of the induction phase. It may be given 2 or more times during the first month of treatment. Intrathecal chemotherapy is usually intensified (given more frequently) during consolidation chemotherapy, and then continued during the maintenance phase and delayed intensification. During these phases, intrathecal chemotherapy may be given as 4–8 doses every 2–3 weeks.
The most common chemotherapy used for low-risk or standard-risk ALL is methotrexate. For higher-risk groups, intrathecal chemotherapy may include methotrexate, cytarabine and hydrocortisone.
Moderate- or high-dose methotrexate may also be given by mouth (orally) or through a needle in a vein (intravenously) as systemic chemotherapy during CNS therapy.
Radiation therapy to the head (called cranial radiation therapy) may sometimes be used as part of CNS therapy. It is usually avoided if at all possible because radiation therapy to the brain can affect growth and development in young children.
Cranial radiation therapy may be given to children who have leukemia cells, or blasts, in the CNS at diagnosis, or those in the high-risk group.
A stem cell transplant may sometimes be used to treat certain cases of childhood ALL. It may be used for:
- ALL that doesn’t respond well to treatment or that recurs soon after it goes into remission
- ALL that is in remission but has a high risk of recurring, or relapsing
- children with Philadelphia chromosome–positive ALL
- rarer forms of ALL (after first remission is reached with induction chemotherapy)
The rarer forms of ALL that may be treated with stem cell transplant are:
- T-cell ALL that does not respond well to chemotherapy
- ALL in infants under the age of 1 year
Many children with leukemia enter a clinical trial that is tailored to their subtype and risk level of ALL. The clinical trial protocol outlines the new combinations and doses of the chemotherapy drugs used.
For more information, go to clinical trials.
Research at the Canadian Centre for Applied Research in Cancer Control led to a new standard in leukemia testing.
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