When leukemia is diagnosed, there are usually about 100 billion leukemia cells in the body. Killing 99.9% of these leukemia cells during the 1-month induction treatment is enough to achieve a remission, but it still leaves about 100 million leukemia cells in the body. These also must be destroyed. An intensive 4- to 6-month program of consolidation treatment and about 2 years of maintenance chemotherapy helps destroy the remaining cancer cells.

As mentioned earlier, children with ALL are divided into risk groups to make sure that the correct types and doses of drugs are given. Treatment will be different for different risk groups.

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.

More than 95% of children with ALL enter remission after 1 month of treatment. This first month of treatment is quite intensive, and you will need to make frequent visits to the doctor. Your child may spend some or much of this time in the hospital, because serious infections can occur. It is very important to take all medicines prescribed. Because of advances in supportive care (nursing care, nutrition, antibiotics, red blood cell and platelet transfusions as needed, etc.), fewer than 3% of children with leukemia die of complications during this initial treatment.

Children with standard-risk ALL often receive 3 drugs for the first month of treatment. These include the chemotherapy drugs L-asparaginase, vincristine, and a steroid (usually dexamethasone). A fourth drug in the anthracycline class (daunorubicin is the one most often used) is typically added for high-risk children. Other drugs that may be given early are methotrexate and/or 6-mercaptopurine.

Intrathecal chemotherapy: All children also need to receive spinal taps to inject chemotherapy into the cerebrospinal fluid (CSF) to kill any leukemia cells that may have spread to the central nervous system. This intrathecal chemotherapy is usually given twice (more often if the leukemia is high risk) during the first month and 4 to 6 times during the next 1 or 2 months. It is then repeated less often during consolidation and maintenance. Usually, methotrexate is used for intrathecal chemotherapy, but drugs called hydrocortisone (a steroid, like prednisone) and cytarabine (ara-C) may be added, particularly in high-risk children.

Along with intrathecal therapy, high-risk patients (for example, those with very high numbers of white blood cells, T-cell ALL, or older children) and those with leukemia cells detected in their CSF when the leukemia is diagnosed may be given radiation therapy to the brain (and possibly the spinal cord). Doctors try to avoid this treatment if possible because no matter how low the dose is kept, it can cause some slight problems in thinking and growth and development. Some doctors feel they can avoid radiation by giving the child very high doses of methotrexate and then neutralizing its side effects with another drug called leucovorin. Others may try more frequent intrathecal treatments.

A possible side effect of the intrathecal treatment is epileptic seizures during treatment, which happen in about 5% to 10% of children. Children who develop seizures are treated with drugs to prevent them.

Consolidation (Intensification)

The next, most "intensive" phase of chemotherapy lasts 4 to 8 months. The consolidation phase reduces the number of leukemia cells still remaining in the body. Several drugs are used in combination to prevent the remaining leukemia cells from developing resistance. Intrathecal therapy (as described above) is continued at this time.

Children with standard-risk ALL are usually treated with drugs such as methotrexate and 6-mercaptopurine or 6-thioguanine, although regimens may differ between cancer centers. Vincristine, L-asparaginase, and/or prednisone may also be added.

Children whose leukemia cells showed high risk factors generally will receive a more intense regimen of chemotherapy. Extra drugs such as L-asparaginase, doxorubicin (Adriamycin), etoposide, cyclophosphamide, and cytarabine (ara-C) are often used and dexamethasone substituted for prednisone. There may be a second round of intense chemotherapy with the same drugs.

Some children, such as those with Philadelphia chromosome-positive ALL, may benefit from a stem cell transplant at this time.

Maintenance

Once induction and consolidation phases of therapy are complete and the leukemia continues to be in remission, maintenance therapy can begin. Most treatment plans use methotrexate and 6-mercaptopurine, given as pills, often along with vincristine, which is given intravenously, and a steroid (prednisone or dexamethasone). These latter 2 drugs are given for brief periods every 4 to 8 weeks.

Occasionally, leukemia patients at higher risk may receive more intensive maintenance chemotherapy and intrathecal therapy.

The total duration of therapy (induction, intensification, and maintenance) for most ALL treatment plans is 2 to 3 years.

Treatment of Residual Disease

All these treatment plans may change if the leukemia hasn't completely disappeared. Several days after treatment has begun the doctor may check the child's bone marrow to see if the leukemia is disappearing. If not, treatment may be intensified or prolonged. If the leukemia seems to have disappeared by standard tests, the doctor may do a special chemical test to look for small numbers of leukemia cells that may be left. If any are found, then once again, chemotherapy may be intensified or prolonged.

Treatment of Recurrent ALL

If a child with ALL relapses, he or she will most likely be treated again with chemotherapy. Much of the treatment strategy depends on how soon the leukemia returns after the first treatment. The shorter the time interval, the greater will be the need for newer and more aggressive chemotherapy.

The most commonly used chemotherapy drugs are vincristine, L-asparaginase, anthracyclines (doxorubicin, daunorubicin), cyclophosphamide, cytarabine (ara-C), and epipodophyllotoxins (etoposide, teniposide). Your child will also receive a steroid (prednisone or dexamethasone) and vincristine unless he or she is known to be resistant to these medications. Intrathecal chemotherapy will also be given.

For children whose leukemia comes back within 6 months of starting therapy or for children with T-cell ALL who relapse, a stem cell transplant may be considered, especially if there is a brother or sister who is a good tissue type match. Stem cell transplant may also be used for other children who relapse after a second course of chemotherapy.

Some children have an extramedullary relapse, meaning that leukemic cells are found in one part of the body (such as the CSF or the testicles) but are not detectable in the bone marrow. In addition to receiving intensive chemotherapy as described above, these children may also have radiation therapy to the affected area (if that area had not been already treated with radiation).

Cure Rates for ALL

The chance of being cured of low-risk ALL is about 85% to 95%, standard-risk is about 65% to 85%, and high-risk ALL is about 60% to 65%.

Philadelphia Chromosome-Type ALL

For children with this high-risk type of leukemia, a stem cell transplant may be advised if induction treatment yields a remission.

Newer, targeted drugs such as imatinib (Gleevec) and dasatinib (Sprycel) are designed to kill leukemia cells that contain the Philadelphia chromosome. These drugs, which are taken as pills and seem to have limited side effects, are now being studied for use along with chemotherapy.