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In the past, systemic combination chemotherapy (chemotherapy given by mouth or through the vein to treat the whole body) plus radiation therapy to the head and spine have been used to prevent cancer of the brain and spine from recurring in children with acute lymphoblastic leukemia (ALL). This led to tremendous progress in the fight against ALL in children; however, the radiation treatment sometimes caused moderate to severe problems with a child’s growth and development, the development of neurologic conditions or second cancers. Now, Israeli researchers report that the use of systemic combination chemotherapy plus combination chemotherapy delivered directly into the spinal cord can help prevent the spreading of cancer to the brain or spine, without the use of radiation therapy.

Childhood acute lymphoblastic leukemia, also called acute lymphocytic leukemia, is the most common cancer occurring in children. ALL is a cancer of the blood, characterized by the presence of too many immature lymphocytes, or white blood cells. Not only can the excess lymphocytes cause swelling in the lymph tissues, but they may also crowd out other important blood cells made by the marrow, such as red blood cells (carry oxygen to the tissues) and platelets (help with blood clotting), preventing these cells from doing their jobs properly. Advanced ALL often involves the brain or spine. The brain and spine are also a common site of recurrence if not properly treated.

Depending on age and other factors, ALL may be treated with chemotherapy and/or radiation therapy. Bone marrow or blood stem cell transplantation is also a standard treatment for selected patients with ALL. Radiation to the brain and spine has been used to prevent spreading of ALL because, in the past, systemic chemotherapy drugs could not penetrate into the fluid surrounding these areas. Since then, systemic chemotherapy drugs that can penetrate into this fluid have been developed, and chemotherapy drugs used locally at the brain and spine are being studied to eliminate the need for radiation therapy.

Researchers in Israel treated 250 children with ALL and who were at either an average or a high risk for suffering a recurrence of leukemia. Patients considered at high risk were those who had a high quantity of leukemia cells in the blood, had a poor response to previous chemotherapy regimens, and/or had certain additional abnormalities of the leukemia cells. The children were placed on an intensive chemotherapy program, consisting of systemic combination chemotherapy plus combination chemotherapy delivered directly into the spinal cord. These patients were followed for an average of 58 months.

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The results showed a 5-year cancer-free survival rate of 74%. A recurrence of ALL in the brain or spine was observed in only 4% of patients; 2% occurring only in the brain or spine and 2% with a generalized relapse. With regard specifically to patients who were considered at high risk for cancer recurrence, the 5-year survival rate without recurrence of cancer was only 48%. Almost 9% of the children at high risk experienced a recurrence in the brain or spine.

The researchers concluded that, in those children who were not at high risk for cancer recurrence, the combination of intensive systemic chemotherapy and chemotherapy delivered directly to the spinal cord was as effective, perhaps even more effective, than the use of systemic chemotherapy with radiation therapy to prevent the recurrence of ALL to the brain and spine. Further study about any long-term effect on a child’s growth and development or neurologic function is needed. (Cancer, Vol 88, No 1, pp 205-216, 2000)

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