Post-remission Treatment

This content has been reviewed and approved by

Hagop M. Kantarjian, MD
Chairman & Professor, Leukemia Department
MD Anderson Cancer Center
University of Texas

Without further treatment, more than 90 percent of patients in remission will have a recurrence of leukemia in weeks or months. To ensure the best outcome, it is important to understand what can make a treatment succeed or fail. Standard post-remission therapy in adults and children typically consists of treatment with more than one cycle of multidrug intensive chemotherapy, or a stem cell transplant combined with treatment (prophylaxis) of the central nervous system and prolonged low-dose "maintenance" chemotherapy for 2 to 3 years.

Because the drugs used in chemotherapy do not cross from the blood into the central nervous system, separate treatment must be used to kill leukemia cells that may enter the brain and nerves.

Risk Factors

The likelihood of a cure for children with acute lymphocytic leukemia (ALL) depends mainly on the intensity of post-remission therapy and the presence of adverse risk factors. The following risk factors may lead to a poor outcome:

• Age less than 1 year or greater than 10
• High white blood cell count
• Cell types:
  • Pre B phenotype
  • FAB L2 phenotype
• Presence of the Philadelphia chromosome
• Blasts (immature cells) in the bone marrow on day 40 after starting therapy

Children and young adults with adverse risk factors may wish to perform an early search for a compatible stem cell donor in case chemotherapy treatment fails. The use of stem cells from a compatible donor is known as allogeneic stem cell transplantation. This procedure involves the placing of donor stem cells into a patient to improve low levels of blood cells caused by high-dose treatment.

It is important to understand your prognosis following standard post-remission therapy. Knowing this will help you to make informed decisions about whether to undergo conventional treatment or to pursue more aggressive or new therapies.

ALL is associated with a genetic abnormality in approximately 50 percent of patients. These genetic abnormalities increase the risk of a poor outcome after standard post-remission treatment. Leukemia recurs in as many as 90 percent to 100 percent of patients with the Philadelphia chromosome.

Other factors, including a high white blood cell count at diagnosis or a prolonged time to achieve an initial complete remission (greater than 4 weeks), also predict a high rate of leukemia recurrence following standard post-remission treatment.

Patients with none of these risk factors have a 60 percent chance of cure with conventional post-remission therapy. These patients may not get additional benefit from more aggressive treatment. Patients with one, two, or three risk factors treated with conventional post-remission therapy, however, have a 35 percent, 25 percent, and 10 percent chance of cure, respectively.

Post-remission therapy with allogeneic stem cell transplantation results in a cure for more than 50 percent of children and young adults. For this treatment, a suitable stem cell donor must be found. Adult patients with adverse risk factors may wish to consider treatment with allogeneic stem cell transplant. It is important for patients with adverse risk factors to identify a suitable allogeneic stem cell donor at the time of diagnosis.

The Importance of Treating the Central Nervous System and Other Sanctuary Sites

ALL cells spread into the central nervous system, testicles, and other locations not easily reached with chemotherapy. These are often referred to as sanctuary sites. This is because many drugs are unable to penetrate into these areas to destroy the cancer cells. The risk of leukemia recurrence can be reduced by injecting chemotherapy drugs into the central nervous system or by treatment with radiation. This is known as central nervous system prophylaxis.

The injection of drugs into the central nervous system is called intrathecal therapy. The chemotherapy drugs methotrexate, or cytarabine, or both are injected through a needle inserted into the spinal canal on several occasions. Without intrathecal therapy, the risk of leukemia recurrence in the central nervous system is 20 percent to 50 percent. This has progressively decreased as more intensive treatments have been developed. The risk of central nervous system recurrence is now only 2 percent to 4 percent, if chemotherapy is injected into the central nervous system according to the treatment plan. Treatment of the central nervous system is therefore standard. Radiation therapy can also be used to prevent leukemia in the central nervous system, but this may cause more long-term side effects, especially in younger patients.

Research is in progress to refine existing treatments and develop new ones. For information on some of the techniques currently under investigation, see Strategies to Improve Treatment.