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The main treatment for children with acute lymphocytic (lymphoblastic) leukemia (ALL) is chemotherapy, which is usually given in 3 main phases:

• Induction
• Consolidation (also called intensification)
• Maintenance

The entire length of treatment is typically about 2 to 3 years, with the most intense treatment in the first few months.

Children with ALL are typically classified by risk group to make sure that the correct types and doses of drugs are given. Treatment may be more or less intense, depending on the risk group.

Induction

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 become normal. (A remission is not necessarily a cure.) More than 95% of children with ALL enter remission after 1 month of induction treatment.

This first month is intense and requires prolonged hospital stays for treatment 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. 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 standard-risk ALL often receive 3 drugs for the first month of treatment. These include the chemotherapy drugs L-asparaginase and vincristine, and a steroid drug (such as dexamethasone). For children in high-risk groups, a fourth chemo drug in the anthracycline class (most often daunorubicin) is typically added. Other drugs that may be given early are methotrexate and/or 6-mercaptopurine.

Children with Philadelphia chromosome-positive ALL may be given a targeted drug such as imatinib (Gleevec) as well. (See below.)

Intrathecal chemotherapy: All children 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). It is usually given twice (or more if the leukemia is high risk or leukemia cells have been found in the CSF) during the first month and several times during the next 1 or 2 months. It is then repeated less often during the rest of treatment.

Usually, methotrexate is the drug used for intrathecal chemo. Hydrocortisone (a steroid) and cytarabine (ara-C) may be added, particularly in high-risk children.

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 if possible, especially in younger children, because no matter how low the dose is kept, it can cause problems with thinking, 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.

Consolidation (intensification)

The next, and usually more intense, 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 the remaining leukemia cells from developing resistance. Intrathecal chemo (as described above) is continued at this time.

Children with standard-risk ALL are usually treated with drugs such as methotrexate, 6-mercaptopurine (6-MP), vincristine, L-asparaginase, and/or prednisone, but regimens differ among cancer centers.

Children with high-risk leukemia (because of gene or chromosome changes in the leukemia cells, for example, or because there is still minimal residual disease after induction) generally get more intense chemo. Extra chemo drugs such as L-asparaginase, doxorubicin (Adriamycin), etoposide, cyclophosphamide, and cytarabine (ara-C) are often used, and dexamethasone is substituted for prednisone.

There may be a second round of intense chemotherapy as part of consolidation. (This is known as delayed intensification.)

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

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.

Maintenance

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 as pills, 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 4 to 8 weeks. Other drugs may be added depending on the type of ALL and the risk of recurrence.

Some children at higher risk may get more intense maintenance chemo and intrathecal therapy.

Treatment of residual disease

The treatment plans may change if the leukemia doesn’t go into remission during induction or consolidation. The doctor will probably check the child’s bone marrow soon after treatment starts to see if the leukemia is going away. If not, treatment might need to be more intense or prolonged.

If standard lab tests show the leukemia seems to have gone away, the doctor may use more sensitive tests to look for even small numbers of remaining leukemia cells (known as minimal residual disease, or MRD). If any are found, chemotherapy again might need to be intensified or prolonged.

If the leukemia remains despite chemotherapy, newer types of immunotherapy such as CAR T-cell therapy or blinatumomab (Blincyto), or the antibody-drug conjugate inotuzumab ozogamicin (Besponsa) might be options.

Treatment of recurrent ALL

If the ALL recurs (comes back) during or after treatment, the child will most likely be treated again with chemotherapy. Much of the treatment strategy depends on how soon the leukemia returns after the first treatment. If the relapse occurs after a long time, the same drugs might still be effective, so the same or similar treatment may be used to try to get the leukemia into a second remission.

If it comes back after a shorter time interval, more aggressive chemo with other drugs may be needed. The most commonly used chemo drugs are vincristine, L-asparaginase, anthracyclines (doxorubicin, daunorubicin, or mitoxantrone), cyclophosphamide, cytarabine (ara-C), and either etoposide or teniposide. The child will also receive a steroid (prednisone or dexamethasone). Intrathecal chemo will also be given.

For children whose leukemia comes back sooner after starting treatment, or for children with T-cell ALL who relapse, a stem cell transplant may be considered, especially if the child has a brother or sister who is a good tissue type match. Stem cell transplants may also be used for children who relapse after a second course of chemotherapy.

Some children have an extramedullary relapse, meaning that leukemia cells are found in one part of the body (such as the cerebrospinal fluid [CSF] or the testicles) but are not detectable in the bone marrow. In addition to intensive chemotherapy as described above, children with spread to the CSF may get more intense intrathecal chemotherapy, sometimes with radiation to the brain and spinal cord (if that area had not been already treated with radiation). Boys with relapse in a testicle may get radiation to the area.

If ALL doesn’t go away completely or if it comes back after a stem cell transplant, newer types of immunotherapy, such as CAR T-cell therapy or blinatumomab (Blincyto), or the antibody-drug conjugate inotuzumab ozogamicin (Besponsa) might be options. 

Philadelphia chromosome-type ALL

For children with certain types of ALL, such as those with the Philadelphia chromosome, standard chemotherapy for ALL (as outlined above) might not be as effective. A stem cell transplant may be advised if induction treatment puts the leukemia in remission and a suitable stem cell donor is available.

Newer, targeted drugs such as imatinib (Gleevec) and dasatinib (Sprycel) are designed to kill leukemia cells that have the Philadelphia chromosome. These drugs are taken as pills. Adding these drugs to chemotherapy throughout treatment seems to help improve outcomes, according to studies done so far.