Treatment During Remission:

Consolidation and maintenance therapies follow induction and first remission. The goal of consolidation and maintenance therapies is to prevent a relapse. The specific treatment choices and degree of aggressiveness after induction therapy depend on a number of factors, particularly the risk factors for relapse.

Consolidation (or Intensification) Therapy

Consolidation therapy is additional treatment that is administered after induction therapy and before maintenance therapy. This is an intense regimen that is designed to prevent the high relapse rates that occur with induction therapy alone. (The benefits of this therapy are clearer in children than in older adults, who may just be given maintenance.)

Consolidation therapy usually continues for about 6 months and uses 1 - 6 courses of chemotherapy, depending on risk factors for relapse.

Examples of consolidation regimens for children at standard risk:

• A limited number of courses of intermediate- or high-dose methotrexate, one of the oldest drugs used for leukemia.
• An anthracycline drug, such as daunorubicin (Cerubidine), used for reinduction followed by cyclophosphamide (Cytoxan, Neosar) 3 months after remission. These are very powerful drugs, but when used in this way toxicity is limited.
• Extended use of an asparaginase drug.

More intense regimens are used for children at high-risk for relapse.

Instead of chemotherapy alone as consolidation therapy, some high-risk patients in first remission who are unlikely to be cured by standard chemotherapy alone may undergo allogeneic stem cell or autologous stem cell bone marrow transplant after the intensive chemotherapy regimens. Many adult patients may fall into this category. Studies on high-risk children have been conflicting about the value of transplants during a first remission.

• Allogeneic transplantation is an option when a well-matched donor is available. Although this treatment can be effective in keeping the leukemia away, significant complications -- such as graft versus host disease, blood clots, liver problems, and lung damage -- can occur and may be a cause of death even without a return of cancer.
• Autologous stem cell bone marrow transplant (using the patient's own bone marrow cells) seems to be helpful also and may be as effective as allogeneic transplantation.

Maintenance

The last phase of treatment is maintenance, or continuation therapy:

• Maintenance therapy typically uses weekly administration of methotrexate (usually in oral form) and daily doses of mercaptopurine.
• Treatment continues for 2 - 3 years for most children with ALL (with the exception of those with mature B-cell leukemia). It is not yet clear if prolonged maintenance therapy benefits adults with ALL.
• If children were not given CNS prophylaxis before, it may be given now.
• Vincristine and a corticosteroid drug (generally dexamethasone) are often added to standard maintenance therapy, although some studies indicate that they do not provide additional benefit.

A maintenance regimen is usually less toxic and easier to tolerate than induction and consolidation. Some studies, however, indicate that overall survival could further be improved with more-aggressive maintenance therapies, including:

• Vincristine and a corticosteroid added to the standard maintenance regimen
• Longer term low-dose maintenance
• Intense regimens similar to induction (called reinduction)

Maintenance is typically ongoing until complete remission has lasted 2 - 3 years.

Investigation is ongoing to determine the best drugs and schedules to use. For example, doctors have debated whether thioguanine is a better choice than mercaptopurine. Researchers are also trying to pinpoint patients who would best benefit from aggressive maintenance treatments.

Risk Factors for Relapse after a First Remission

The following are factors that increase the risk for relapse after initial treatments:

• Microscopic evidence of leukemia after 20 weeks of therapy (minimal disease)
• Age over 30
• A high white blood cell count at the time of diagnosis
• Disease that has spread beyond the bone marrow to other organs
• Certain genetic abnormalities, such as the presence of the Philadelphia chromosome or MLL gene translocations
• Patients with high disease levels after 7 - 14 days of induction therapy
• The need for 4 or more weeks of induction chemotherapy in order to achieve a first complete remission

Patients with one or more of these risk factors may be candidates for bone marrow transplantation once they are in first remission.