Acute lymphoblastic leukemia (ALL): chemotherapy phases

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Learn what happens during each of the five phases of chemotherapy for acute lymphoblastic leukemia (ALL).

Key points

  • Chemotherapy for children with acute lymphoblastic leukemia (ALL) is divided into induction, consolidation, interim maintenance, delayed intensification, and maintenance phases.
  • There is a high likelihood that leukemia will return if maintenance phase is not completed.

The goal of treatment is to completely destroy leukemic cells and stop the bone marrow from producing any more cancerous cells.

To treat ALL, your child’s chemotherapy is divided into five different phases.

Each phase differs in length and the type of medicines that are used. Some of the drugs listed for each treatment phase may differ slightly from your child’s protocol.

1. Induction phase

The aim of induction therapy is to destroy leukemic cells and get your child into morphologic remission. This means that less than 5% of your child’s bone marrow cells are leukemic and a normal amount of white blood cells, red blood cells, and platelets are being produced.

How is your child’s progress monitored during induction?

Your child’s doctor will perform a bone marrow test on the 29th day of your child’s treatment. This test is called a minimal residue disease (MRD) test. It looks at how well the treatment is destroying the leukemia cells by measuring the number of leukemia cells left inside your child’s bone marrow. This information will help the oncologist decide on your child’s ALL risk category and subsequent treatment plan.

It is important to note that the MRD test can only measure detectable leukemia cells. We know that even if the MRD test is negative, there are still undetectable leukemia cells after completing induction chemotherapy. This is why more phases of treatment are required.

What do the MRD values mean?

  • If your child is MRD positive, they still have detectable leukemia cells inside their bone marrow.
  • A negative MRD value (less than 0.01%) means that your child may still have leukemic cells left in their bone marrow, but we cannot detect these leukemic cells by current methods.

Depending on the MRD value, your doctor might change the treatment plan to make sure your child receives the most effective course of treatment. Children with positive MRD are categorized as high-risk or very high-risk ALL. They may undergo more intense chemotherapy or may be recommended to have a bone marrow transplant (BMT).

How long does induction last?

Induction therapy usually lasts for 29 days followed by a 1-week rest from chemotherapy.

During induction, drugs will be given intravenously (IV) or through an intrathecal (IT) or orally (by mouth):

  • If a drug is given intravenously, an IV is used to deliver medicine directly into your child’s vein. To set up an IV, a nurse will place a hollow needle into a vein in your child’s hand or arm. Once they have found they vein, they remove the needle and insert the IV. The IV is a hollow tube that is placed in the vein and attaches to a longer tube, which connects to the IV pump and delivers medicine into your child’s vein.
  • Intrathecal (IT) is an injection into the spinal fluid around your child's spinal cord by a nurse or a doctor. It is given as a single injection or by using a catheter and a pump.

Medicines used during induction

Usually, all of the following drugs are given during induction:

  • cytarabine (ARA-C), intrathecal (IT)
  • methotrexate (MTX), IT
  • dexamethasone (DEX) or prednisone (PRED), by mouth
  • vincristine (VCR), intravenous (IV)
  • asparaginase (ASP) or PEG-asparaginase (PEG-ASP), intravenous (IV)
  • daunorubicin (DAUN), IV; this medicine is only used for children with high-risk ALL

2. Consolidation phase

After completing induction therapy, your child starts the consolidation phase. Although there may not be detectable leukemia cells in your child’s blood or bone marrow at the end of induction, there still might be some leukemia cells that doctors cannot detect. This is why the treatment continues.

The consolidation phase lasts for 4 to 8 weeks, depending on the ALL risk type and protocol.

Your child may take the following medicines:

  • methotrexate (MTX), IT
  • mercaptopurine (6-MP), by mouth
  • vincristine (VCR), IV
  • cyclophosphamide, IV
  • cytarabine (ARA-C), IV
  • PEG-asparaginase, IV

3. Interim maintenance phase

After consolidation, the next phase is interim maintenance. This phase aims to destroy any leukemic cells left in your child’s marrow or blood. This phase lasts about 8 weeks.

Your child may take the following medicines:

  • methotrexate (MTX), IV and IT
  • mercaptopurine (6-MP), by mouth
  • vincristine (VCR), IV

4. Delayed intensification phase

Delayed intensification is similar to another induction and consolidation phase and lasts for 8 weeks. This phase is important because it can improve a child’s event-free survival, which is the period after treatment in which a patient does not experience cancer symptoms or recurrence.

During delayed intensification phase, your child may take the following medicines:

  • methotrexate (MTX), IT
  • dexamethasone (DEX), by mouth
  • thioguanine (6-TG), by mouth
  • vincristine (VCR), IV
  • doxorubicin (DOXO), IV
  • PEG-asparaginase (PEG-ASP), IV
  • cyclophosphamide (CPM), IV
  • cytarabine (ARA-C), IV

5. Maintenance phase

In maintenance phase, there are still no detectable leukemic cells in your child’s marrow or blood. However, this phase must be completed because cancerous cells may still be present, even if we cannot see them. Maintenance occurs for all leukemia patients after completing the previous phases, unless doctors suspect your child has relapsed.

Each cycle of maintenance lasts for 84 days. Cycles are repeated until the duration of therapy from the start of interim maintenance is 2 years for girls and 3 years for boys.

As with all phases following induction therapy, the goal of maintenance is to consolidate and maintain remission. There is a high likelihood that the leukemia will return if this phase is not completed. For this reason, it is very important that your child takes all medicines as instructed.

During maintenance, your child takes all of the following medicines:

  • methotrexate (MTX), IT
  • dexamethasone (DEX) or prednisone (PRED), by mouth
  • 6-mercaptopurine (6-MP), by mouth
  • methotrexate (MTX), by mouth
  • vincristine (VCR), IV

What is maintenance like?

Your child receives intravenous chemotherapy on a schedule determined by your child’s protocol. They take chemotherapy medicines by mouth every night at home, and come into the hospital to:

  • receive blood-work to check complete blood counts (CBC) every 2 to 4 weeks
  • take vincristine intravenously every 4 weeks
  • start a course of steroids (dexamethasone or prednisone) every 4 weeks
  • receive a lumbar puncture so that doctors can give your child intrathecal chemotherapy, once every 3 months

Blood work is important because doctors need to make sure that the amount of your child’s white blood cells (neutrophils) are not too high or too low. If they are too low, then the chemotherapy is killing too many marrow cells, making your child neutropenic and at risk for developing an infection. If the amount of neutrophils is too high, then the therapy is not killing enough hidden leukemia cells. For this reason, making sure your child takes 6-mercaptopurine orally every day and methotrexate orally every week, without missing doses, is essential to ensure your child stays in remission and reduce the risk of relapse.

How can you help your child keep a healthy lifestyle during maintenance?

During maintenance, your child needs to maintain a healthy lifestyle. Encourage your child to eat nutritious food and to participate in daily exercise. Physical activity is very important to minimize your child’s risk of becoming overweight or obese, which can be a long-term side-effect of the treatment. In addition, exercise can also prevent muscle wasting (decrease in muscle mass) and help maintain bone health during treatment phases when steroids need to be used. Typically, there are no restrictions on physical activity during maintenance chemotherapy, even though the central line is still in place. Talk to your child’s treatment team to discuss your child’s physical activity options.

For more information, please visit Good nutrition during leukemia treatment.

Last updated: Machi 6th 2018