Researchers Work to Improve Treatment for Pediatric Leukemia


Researchers at Dell Pediatric Research Institute, working closely with doctors at Dell Children’s Medical Center of Central Texas, have received a $250,000 grant to seek ways to improve treatment and improve the survival rates of children diagnosed with two common forms of pediatric leukemia.

Ultimately, the researchers hope to better predict which patients will not respond well to treatment. Being able to foresee potential resistance to traditional treatment protocols gives doctors a way to improve treatment and overcome that resistance.

The grant is one of 40 awarded nationally for 2014 as part of the Hyundai Hope Grant Program.

University of Texas researchers are working to identify new metabolic biomarkers that will better predict patients’ response to cancer treatment drugs. They are: Stefano Tiziani, assistant professor in the Department of Nutritional Sciences, College of Natural Sciences and adjunct assistant professor at the School of Medicine, The University of Texas Health Science Center, San Antonio; Philip Neff pediatric hematologist and oncologist with Children’s Blood & Cancer Center at Dell Children’s; and John DiGiovanni, a cancer researcher who is a professor in the Division of Pharmacology and Toxicology of the College of Pharmacy and in the Department of Nutritional Sciences of the College of Natural Sciences.

Using state-of-the-art methods to examine blood and bone marrow samples taken before and after the course of treatment from children diagnosed with acute lymphoblastic (ALL) or acute myeloid (AML) leukemias, the scientists will profile changes in cancer cell metabolism.

“Results of this exciting bench research — the first of its kind ever — will provide the first step toward the development of new strategies for cancer therapy design,” says Tiziani. “We foresee that the innovative combined use of the metabolic status and other current clinical parameters will allow the timely design of targeted and personalized protocols not only for treatment of childhood leukemia patients, but also other pediatric diseases.”

The researchers’ first goal is to analyze samples — taken shortly after diagnosis but before treatment begins — to identify new metabolic biomarkers, small molecules unique to cancer cells’ metabolism that serve as chemical targets for treatment. Aided by high-resolution magnetic resonance spectroscopy and mass spectrometry, researchers will measure the types and amounts of metabolites produced by cancer cells to determine the best molecular targets for treatment.

“This collaborative research is the first step toward the development of new strategies for cancer therapy,” says Neff. “Using the patients’ blood and actual cancer cells to create a metabolic profile will greatly improve the understanding of the drugs and how they are used in therapy. This could result in higher survival rates in children with leukemia, with less chance of relapse and with fewer side effects.”

“We need better predictors for treating these patients. While the treatment regimens for ALL are quite effective, with high cure rates, there is still a risk of relapse or resistance to treatment,” says DiGiovanni. “We want to know what it is about those kids, what makes them more prone to resistance and/or relapse and how we can best identify them earlier in the course of treatment.”

With a new set of promising disease metabolism biomarkers, the researchers will analyze a set of samples taken after disease remission, the point at which the numbers of abnormal cells in the blood and bone marrow cease to be present in observable numbers. The metabolic profiles of the remission samples will give scientists and doctors a road map for consolidation therapy, the treatments intended to keep patients in remission, and will suggest new combinations of treatments.

Dell Children’s Medical Center and the Dell Pediatric Research Institute are located within 50 yards of each other and offer a prime collaborative environment of frontline treatment physicians and accomplished university bench researchers. These centers are ideally positioned to develop a robust metabolomic program for personalized pediatric cancer therapy and make important contributions to improving therapeutic responses in children suffering from hematological malignancies. The Dell Medical School at The University of Texas at Austin will support and extend this type of collaboration.