Testing of Cancer Cell Helps Identify Children In Need of Aggressive Treatment

Childhood AML: Testing of Cancer Cell Genetics Helps Identify Children In Need of Aggressive Treatment.

Children who have acute myeloid leukemia (AML) are most commonly treated with chemotherapy, and 30 to 50% are cured. Importantly, 80% of children with AML have genetic abnormalities that can be detected in the leukemia cells. These abnormalities, usually affecting 1 or more chromosomes, are often associated with different responses to the standard chemotherapy treatment. Now, researchers from the Pediatric Oncology Group Study say that by identifying which leukemia cell genetic abnormalities are associated with a poorer response to the current treatment, children with these types of cells can be offered alternative treatment options.

Acute myeloid leukemia is a cancer of the blood cells in the bone marrow. The bone marrow contains early blood-forming cells, called stem cells, which grow and mature into the 3 blood cell types: white blood cells (protect the body from infection), red blood cells (carry oxygen to the tissues), and platelets (help the blood to clot). In the case of leukemia, too many cells of 1 type are produced in the bone marrow, resulting in an excess of abnormal, immature cells of this type. These cells crowd out other blood cells, and may invade other parts of the body, including the blood stream, lymph system, and vital organs. There are 2 types of myeloid leukemia, acute and chronic. Acute myeloid leukemia progresses more quickly than the chronic type. Treatment is usually chemotherapy, but may also include radiation therapy, biologic therapy to help the immune system, or high-dose chemotherapy followed by a procedure called a stem cell transplantation. A stem cell transplantation involves an infusion of stem cells, given to the child after receiving high-dose chemotherapy, to help “rescue” the bone marrow and replace blood cells that are destroyed by the high-dose chemotherapy.

Researchers from the Pediatric Oncology Group Study evaluated the leukemia cell genetics and the treatment outcomes of 478 children with AML. For children who had a genetic abnormality related to an inverted chromosome 16, 4-year survival without relapse (return) of the cancer was 58%. For children with a switch, or translocation, of chromosomes 8 and 21, 4-year survival without relapse was 45%. Also for those with no leukemia cell genetic abnormalities, 4-year survival without relapse was 45%. For children having a switch, or translocation, of chromosomes 15 and 17, 4-year survival without relapse was only 20%; for those with an abnormality called 11q23, only 24%.

These findings suggest that children with leukemia cell genetic abnormalities that are associated with a poorer outcome—such as those with a translocation of chromosomes 15 and 17 and those with a 11q23 abnormality—should be considered for therapies other than the standard chemotherapy regimen. Parents may wish to speak with their child’s doctor about the risks and benefits of treatment with a higher dose of chemotherapy, given with a stem cell transplantation, or of participation in a clinical trial in which a new therapy is being studied for childhood AML. (Blood, Vol 94, No 11, pp 3707-3716, 1999)

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