Researchers Study New Drug Combinations to Treat Childhood Leukemia

Scientists from the Barbara Ann Karmanos Cancer Institute in Detroit presented data today at the American Association for Cancer Research's 100th Annual Meeting 2009 that could potentially provide a brighter future for children who suffer from a more deadly form of acute leukemia.

Yubin Ge and Chengzhi Xie presented work at the conference revealing that a combination of FDA-approved drugs works synergistically to help children with acute myeloid leukemia (AML). Ge is an assistant professor at the Karmanos Cancer Institute and at the Wayne State University School of Medicine's Department of Pediatrics. Xie is a postdoctoral fellow with the Developmental Therapeutics Program at Karmanos Cancer Institute and Wayne State University School of Medicine. He also is a lecturer with the College of Life Science at Jilin University in Changchun, China.

AML, which originates in bone marrow, accounts for one-fourth of acute leukemia in children and is responsible for more than half of the leukemia deaths in this population. Approximately 600 children are diagnosed with AML each year, according to Ge and presently there is no effective drug treatment for those children should they relapse.

"Right now, we are at a bottleneck," Ge says. "We really want to find a better treatment for those relapsed cases."

Ge and fellow researchers considered drugs that are already FDA-approved to help fight AML. Resistance among patients to FDA-approved cytarabine is a major cause of treatment failure in AML. Scientists considered clofarabine, approved by the FDA in 2004, and paired it with valproic acid (VPA), typically used to treat epilepsy. They found the two drugs worked together to dramatically stimulate cell death.

"We considered an old drug for a new use," Ge says. "It looks like the increased drug activity or synergy is not due to the transport or delivery of clofarabine, but to enhanced cell death. We were so pleased with the results."

AML afflicts mostly adults -- about 10,000 new cases each year -- and strikes older children. Acute lymphoblastic leukemia usually affects children between the ages of 2 to 5 and is generally easier to treat. Treatment advancements for AML, however, have been less successful.

Ge says that researchers at Karmanos discovered the synergy between VPA and clofarabine only a few months ago, though departmental research has spanned some 15 years in the field of treating childhood leukemias. The current research represents a unique partnership between Ge, his Karmanos colleagues, and Dr. Jeffrey Taub, M.D., a pediatric oncologist at Children's Hospital of Michigan, also in Detroit.

Ge expects that their findings will move into the clinical phase in the next few years. St. Jude Children's Research Hospital in Memphis, Tenn. Is now conducting its own clinical drug trial studying the combined effects of VPA and cytarabine to treat newly diagnosed AML patients 21 years old and younger.

"This is truly translational research," Ge says. "We really want to translate what we do in the laboratory to the clinic and hopefully save more lives."

Located in mid-town Detroit, Mich., the Barbara Ann Karmanos Cancer Institute is one of 40 National Cancer Institute-designated comprehensive cancer centers in the United States. Caring for more than 6,000 new patients annually on a budget of $216 million, conducting more than 700 cancer-specific scientific investigation programs and clinical trials, the Karmanos Cancer Institute is among the nation's best cancer centers.

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