Treatment of Children with Acute Lymphocytic Leukemia (ALL)

The goal of induction chemotherapy is to achieve a remission. This means that leukemia cells are no longer found in bone marrow samples, the normal marrow cells return, and the blood counts improve. (A remission is not necessarily a cure.) More than 95% of children with ALL enter remission after 4 weeks of induction treatment.

This first month of treatment is intense and requires hospital stays and frequent visits to the doctor. Your child may spend some or much of this time in the hospital, because serious infections or other complications can occur. It is very important to take all medicines as prescribed and tell your care team about any new symptoms, such as a fever. Sometimes complications can be serious enough to be life threatening, but in recent years, advances in supportive care (nursing care, nutrition, antibiotics, red blood cell and platelet transfusions as needed, etc.) have made these much less common than in the past.

Children with ALL may receive 3 or 4 chemo drugs for the first 4 weeks of treatment. These include asparaginase, vincristine, steroids (such as prednisone or dexamethasone) and, in some cases, a fourth drug in the anthracycline class (daunorubicin or doxorubicin). Whether 3 or 4 drugs are used may depend on the type of ALL, ALL risk group, and routine practice at your treatment center.

Children with Philadelphia chromosome-positive ALL may be given a targeted drug, such as imatinib or dasatinib, as well.

Intrathecal chemotherapy: All children with ALL also get chemo into the cerebrospinal fluid (CSF) to kill any leukemia cells that might have spread to the brain and spinal cord. This treatment, known as intrathecal chemotherapy, is given through a lumbar puncture (spinal tap). This treatment starts during induction and is often given in the later phases of treatment as well. How often intrathecal chemo is given depends on a few factors like risk group and whether or not leukemia cells were found in the CSF at the time the leukemia was diagnosed.

Some cancer centers use methotrexate or cytarabine for intrathecal chemo doses, and others may use a combination of methotrexate, hydrocortisone, and cytarabine (called triple intrathecal chemo). Triple intrathecal chemo is more common in the treatment of children with higher-risk ALL.

Along with intrathecal chemo, some high-risk patients (for example, those with T-cell ALL and those with many leukemia cells in their CSF when the leukemia is diagnosed) may be given radiation therapy to the brain. This was more common in the past, but recent studies have found that many children, even with high-risk ALL, may not need radiation therapy if they are given more intensive chemo. Doctors try to avoid giving radiation to the brain, especially in younger children, because no matter how low the dose is kept, it can cause problems with thinking, learning, growth, and development.

A possible side effect of intrathecal chemo is seizures during treatment, which happen in a small percentage of children. Children who develop seizures are treated with drugs to prevent them.

The consolidation phase of chemo starts once the leukemia is in remission and typically lasts for several months. This phase further reduces the number of leukemia cells still in the body. Several chemo drugs are combined to help prevent any remaining leukemia cells from developing resistance. Intrathecal chemo (as described above) is continued during this time.

During consolidation, children may be treated with drugs such as methotrexate, cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), vincristine, asparaginase, doxorubicin, and/or steroids, but regimens differ among cancer centers. Children with T-cell ALL may be treated with nelarabine during this phase as well.

Children with high-risk leukemia, because of gene or chromosome changes in the leukemia cells or because there is still minimal residual disease after induction, generally get more intense treatment and higher doses of certain chemo drugs over the treatment course.

For some children with ALL, there may be other rounds of intense chemotherapy as part of consolidation. These are known as delayed intensification and interim maintenance.

Children with Philadelphia chromosome-positive ALL may also get a targeted drug such as imatinib (Gleevec).

For some children with B-cell ALL, the immunotherapy drug blinatumomab (Blincyto) might be part of the consolidation phase as well.

For some children in high-risk groups, a stem cell transplant might be an option at this time once the leukemia is in remission.

If the leukemia remains in remission after induction and consolidation, maintenance therapy can begin. Most treatment plans use daily 6-mercaptopurine (6-MP) and weekly methotrexate, given by mouth, often along with vincristine, which is given into a vein (IV), and a steroid (prednisone or dexamethasone). These latter 2 drugs are given for brief periods every 12 weeks. Other drugs may be added depending on the type of ALL and the risk of recurrence. Intrathecal chemo continues during maintenance treatment.

Maintenance can last up to 2 years. For most children, maintenance chemo can be given in the clinic or at home. Some children at higher risk may get more intense maintenance chemo and intrathecal therapy.