Novel, even unlikely drugs may curb childhood leukemia

ul in other cancers as well."

Blocking cancer signals

News reports over the past year have heralded highly encouraging results from clinical trials of Glivec (STI-571) for adults with chronic myeloid leukemia (CML). Glivec represents a new class of drugs called signal transduction inhibitors that block the signaling pathways that cause cancer cells to grow. It is bioengineered to zero in on a cell receptor present in leukemia cells that carry a genetic defect called the Philadelphia chromosome.

This targeted approach causes minimal side effects to healthy tissue. While CML is rare in children, the same genetic defect found in CML, the Philadelphia chromosome, occurs in an aggressive form of childhood acute lymphoblastic leukemia (ALL).

Directed by Dr. Lange, Childrens Hospital is testing Glivec against that treatment-resistant form of ALL. Through its participation in the Childrens Oncology Group, a collaborative national organization that pools data and expertise from many cooperating cancer centers, Childrens Hospital is currently conducting pediatric trials of the drug. Because studies have suggested Glivec may have wider applications against other types of cancer, Childrens Hospital will test it later this year in children with highly malignant brain tumors.

Boosting immune effects

Also under the umbrella of the Childrens Oncology Group, Dr. Lange is leading tests of interleukin-2 (IL-2), a compound that occurs naturally in the body. IL-2 is an immune system protein that plays an important role in an immune response that occurs after a bone marrow transplant. In the "graft vs. leukemia effect," IL-2 stimulates the bodys natural killer cells to attack leukemia cells and drive the disease into remission.

The pediatric clinical trials led by Dr. Lange will test whether providing IL-2 can confer this benefit against acute myeloid leukemia (AML) in the absence of a marrow transplant. If so, said Dr. Lange, the approach may

Contact: John Ascenzi
Children's Hospital of Philadelphia

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