Treatment During Remission
Consolidation and maintenance therapies follow induction and first remission in order 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 approximately six months and uses one to six 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 agent, such as daunorubicin (Cerubidine), used for reinduction followed by cyclophosphamide (Cytoxan, Neosar) three months after remission. These are very powerful drugs, but when used in this way toxicity is limited.
More intense regimens are used for children at high-risk for relapse.
Maintenance
The last phase of treatment is maintenance, or continuation therapy, which involves the following:
- Maintenance therapy typically uses weekly administration of methotrexate (usually in oral form) and daily doses of mercaptopurine. (Mercaptopurine should be given in the evening.)
- Treatment continues for between two and three 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.
A maintenance regimen is usually less toxic and easier to tolerate than induction and consolidation. Some studies, however, are showing that overall survival could further be improved with more-aggressive maintenance therapies, including the following:
- Pulses of vincristine and a corticosteroid added to the standard maintenance regimen. (One 2000 study reported that the intensive use of the corticosteroid prednisone caused severe bone damage and significant disability in 84% of children on this regimen. Dexamethasone is preferred in children.)
- Longer term low-dose maintenance.
- Intense regimens similar to induction (called reinduction).
Maintenance typically continues until continuous complete remission has lasted two to three years.
Investigation is ongoing to determine the optimal agents and schedules to use. For example, the agent thioguanine may be a more effective 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 (called minimal disease). (Advanced diagnostic techniques called polymerase chain reaction (PCR) tests are used for detection.)
- 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 seven to 14 days of induction therapy.
- The need for four or more weeks of induction chemotherapy in order to achieve a first complete remission. (One study suggested that a poor response, specifically to corticosteroids used in initial treatment, was a strong predictor for relapse.)
Patients with one or more of these risk factors may be candidates for bone marrow transplantation once they are in first remission.
Investigative Indicators for Predicting Relapse
A 2001 study suggested that test results showing elevated levels of a peptide called glutathione in blast cells may indicate a higher risk for relapse after treatment.
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