Acute Lymphocytic Leukemia - Treatment to Achieve Remission

Preventing Central Nervous System Disease (CNS Prophylaxis)

CNS prophylaxis is critical for preventing disease that has spread to the brain, spine, and testes (called sanctuary disease sites). Although only 3% of children with ALL have evidence of leukemia in the central nervous system (CNS) at the time of diagnosis, leukemia will spread to this region in between 50 - 70% of children without preventive (prophylactic) treatment. The brain is one of the first sites for relapsing leukemia.

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CNS prophylaxis is usually:

Administered together with induction therapy before moving to consolidation, the next standard treatment phase, particularly if there are any leukemic cells detected in the spinal fluid.
Given through intrathecal chemotherapy, in which a drug is injected directly into the spinal fluid. The drugs used are either methotrexate alone or a combination of methotrexate, hydrocortisone, and cytarabine. (Induction chemotherapy does not penetrate the blood-brain barrier sufficiently to destroy leukemic cells in the brain.)
In some cases, methotrexate, with or without other drugs, is given as systemic (widespread) therapy at the same time as intrathecal chemotherapy. The addition of this treatment is effective in preventing relapse in the central nervous system and can substitute for radiation to the skull.

Cranial Radiation Therapy. Some high-risk children also receive radiation to the skull (cranial irradiation), radiation to the spine, or both at the same time. This combination can be very toxic and can cause later learning problems. It is generally used only in children who have evidence of the disease in the central nervous system at the time of diagnosis. Later complications can include learning and neurologic problems. Using lower-dose units of radiation, however, is proving to be effective and to significantly reduce the risk for mental impairment. Cranial radiation is also associated with later risk factors for heart disease.

A 2003 study reported the long-term effects of cranial or craniospinal radiation therapy during initial treatment for ALL. Among patients who achieved at least 10 years of event-free survival, those who received radiation therapy had a significantly higher risk of a second neoplasm, a slightly elevated mortality rate, and higher unemployment rate than patients who did not receive radiation therapy.

Indications for Remission after Induction Treatment

Survival in acute leukemia depends on complete remission. Although is not always clear-cut, remission is indicated by the following:

All signs and symptoms of leukemia disappear.
There are no abnormal cells in the blood, bone marrow, and cerebrospinal fluid.
The percentage of blast cells in the bone marrow is less than 5%.
Blood platelet count returns to normal.

Induction can produce extremely rapid results and the faster the time to remission the better the outlook:

A complete remission usually occurs within the first4 weeks. Patients who show low disease levels within7 to 14 days have an excellent outlook, particularly if they have favorable genetic factors, and may need less-intensive treatments afterward.
Patients with high disease levels at 14 days or who require more than4 weeks to achieve remission are at higher risk for relapse and most likely need more aggressive treatment.
According to a 2002 study, the timing of blood platelet recovery may be a simple and important way of predicting remission. The quicker the recovery, the more likely the patient will achieve a complete remission.