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Family Matters - Fall 2008

New Approaches Found Against Leukemia and Other Pediatric Cancers

Several pediatric oncologists from the Children’s Cancer Hospital at M. D. Anderson traveled across the country this summer to deliver research findings that could possibly be used to fight pediatric cancer while minimizing side effects.

First Stop: Cincinnati, Ohio – ASPHO Conference

Three researchers from the Children’s Cancer Hospital were selected to give oral presentations of their work on childhood cancer at the annual American Society of Pediatric Hematology/Oncology (ASPHO) conference, the premier conference for pediatric hematologists and oncologists worldwide.

Expanding Natural Killer Cells from Cord Blood to Fight Leukemia

Patrick Zweidler-McKay, M.D., Ph.D., assistant professor of pediatrics, and his collaborators identified how immune cells from umbilical cord blood, called natural killer (NK) cells, could be increased and used to kill human leukemia cells in mice.
When given to mice with aggressive human leukemias, these NK cells reduced the circulating leukemia cells by 60% to 85%.

“Cord blood is a promising source of natural killer cells because the NK cells have enhanced sensitivity to stimulation, decreased potential to cause graft-versus-host disease and are available from cord banks throughout the country and world,” Zweidler-McKay says.

Bolstering NK Cells’ Ability to Fight Cancer When Transplanted

Also investigating the therapeutic potential of NK cells is Dean Lee, M.D., Ph.D., assistant professor of pediatrics. Lee identified a drug therapy that may make NK cells more effective once transplanted.

Relapsed and metastatic osteosarcomas often are not sensitive to chemotherapy or radiation, but several studies have suggested these tumors may be immunologically responsive.

Lee’s study showed that combining a certain drug, MS-275, with NK cells increases their killing ability and makes osteosarcoma cells more sensitive to NK cells.

“Traditional chemotherapy drugs kill any fast-growing cells like cancer, but they also kill healthy fast-growing cells like hair, bone marrow and mucous membranes, making the drugs very toxic,” says Lee, senior investigator on the study. “There’s a new class of drugs that takes cells that aren’t properly regulated and makes them behave. In our study, we found that these drugs make tumor cells more recognizable and vulnerable to natural killer cells.”

Delivering a One-Two Punch Against Leukemia

Post-doctoral fellow Lauren Akers, D.O., working with Zweidler-McKay, found a different way to fight leukemia in her preclinical research. Akers found that combining a glycolysis inhibitor, 3-BrOP, with another drug, rapamycin, induced more than 90% cell death in human tissue cultures of acute lymphocytic leukemia.

Glycolysis is a process that turns glucose into energy for cells. Unlike healthy cells that get their energy for growth from both glycolysis and respiration, cancer cells are highly dependent on glycolysis. Using the M. D. Anderson-developed drug, 3-BrOP, researchers inhibited glycolysis, thus starving the leukemia cells from their energy source while leaving healthy cells free to get their energy from respiration.

Rapamycin is an mTOR inhibitor that keeps cancer cells from coping with stress, thus resulting in cell death. When researchers on the study combined the two drugs, they discovered a synergistic effect.

Second Stop: Chicago, Illinois – ASCO Meeting

Two weeks after ASPHO and two states over, Dennis Hughes, M.D., Ph.D., traveled to the windy city for the 44th American Society of Clinical Oncology (ASCO) annual meeting. Hughes presented comprehensive therapeutic practices to treat pediatric bone cancer patients with poor prognosis due to tumor metastasis in the heart, central nervous system and mediastinal areas.

“When patients relapse or metastasize in rare locations, standard treatment is no longer an effective option,” says Hughes, assistant professor of pediatrics from the Children’s Cancer Hospital at M. D. Anderson. “Bringing together a multidisciplinary team of pediatric oncologists, radiation oncologists and specialized surgeons, we can offer some patients unique treatments that give them longer survival with a quality of life they wouldn’t have had otherwise.”

Cardiac tumors are very rare in children. Hughes collaborated with senior investigator on the study, William Douglas, M.D., from Children’s Memorial Hermann Hospital in Houston, who surgically removed the cardiac tumors. As a result of their success, the two are collaborating to develop a pediatric cardiac tumor program for children with benign and malignant tumors.

Third Stop: Los Angeles, California – Cord Blood Symposium

As Hughes was returning from ASCO, Zweidler-McKay was back in the air – this time flying to Los Angeles for the International Umbilical Cord Blood Transplantation Symposium.

At the symposium, Zweidler-McKay presented a new process that “sugarcoats” cord blood cells to make them engraft faster and more efficiently when used for stem cell transplantation in mice. Co-investigators Shpall and Simon Robinson of the Department of Stem Cell Transplantation and Cellular Therapy at M. D. Anderson have helped pioneer this approach that combines the sugar, fucose, with a special enzyme, EngraftinTM.

In comparison to cells from bone marrow, previous research has shown that cord blood cells often take longer to engraft to the recipient’s bone marrow. This puts the patient at higher risk for infection due to low blood counts. In some cases, there aren’t enough cord blood cells that make it to the bone marrow resulting in cord blood transplant failure.

If Zweidler-McKay’s process shows to be effective when used in clinical trials in patients, then it will overcome these potential disadvantages to cord blood transplant and further enhance the opportunities for using cord blood transplants to fight cancer.

More Stops to Come

The pediatric oncology researchers mentioned here, and others like them, have many more “stops” scheduled in the years to come. Their work at the Children’s Cancer Hospital at M. D. Anderson is the future of pediatric cancer treatment and the hope of all pediatric cancer patients and their families.




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