As mentioned, chemotherapy given intravenously or orally does not penetrate the blood-brain barrier sufficiently to destroy leukemic cells in the brain. Since the brain is one of the first sites for relapsing leukemia, preventive treatment is administered to the brain, spine, and testes (called sanctuary disease sites). This is called CNS prophylaxis.

For children, CNS prophylaxis uses intrathecal chemotherapy, in which a drug is injected directly into the spinal fluid. Intrathecal chemotherapy is given with methotrexate alone or a combination of methotrexate (MTX), cytarabine, and hydrocortisone.

Some high-risk children also receive radiation to the skull (cranial radiation), radiation to the spine, or both at the same time. This combination can be very toxic and is generally used only in children who have evidence of the disease in the central nervous system at the time of diagnosis. Later complications of higher-dose cranial radiation can include learning and neurologic problems. Cranial radiation is also associated with increased risks for stroke and secondary cancers.

Adult CNS prophylaxis is performed in one of three ways:

• Cranial radiation plus intrathecal chemotherapy with methotrexate
• High-dose systemic infusion of methotrexate plus intrathecal methotrexate without cranial radiation
• Intrathecal methotrexate chemotherapy alone

Evidence of Remission after Induction Treatment

Survival in acute leukemia depends on complete remission (no signs of active cancer). Although 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. Nearly all children with ALL achieve remission after a month of induction treatment. The shorter the time to remission the better the outlook:

• A complete remission usually occurs within the first 4 weeks. Patients who show low disease levels within 7 - 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 than 4 weeks to achieve remission are at higher risk for relapse and most likely need more aggressive treatment.

Side Effects and Complications

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Review Date: 01/27/2011
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org)