In Bid to Make Child Cancer Treatments Safer, Scientists Find Possible Warning Signs of Severe Reaction

Scientists seeking a way to eliminate an adverse reaction to treatments for acute lymphocytic leukemia, a common childhood cancer, have found what they believe to be an early warning indicator.

Mouse studies conducted by Rutgers researchers as part of a larger scientific team are pointing to vitamin A levels as a signal that a patient may or may not be vulnerable to a dangerous toxicity.

Summarizing their findings in Science Translational Medicine, the scientists found that, in patients being treated for acute lymphocytic leukemia with the chemotherapy drug asparaginase, there is an association between low levels of vitamin A and the development of pancreatitis. The results also suggest that increasing levels of vitamin A in the diet may reduce the risk of developing pancreatitis.

“These findings are important because they serve as a possible tool to aid in improving the safety of chemotherapy treatment in patients diagnosed with acute lymphocytic leukemia,” said study author Tracy Anthony, a professor in the Department of Nutritional Sciences in the Rutgers School of Environmental and Biological Sciences (SEBS) and a researcher in the Cancer Metabolism and Immunology Research Program at Rutgers Cancer Institute of New Jersey.

“Asparaginase is viewed as a powerful weapon against acute lymphocytic leukemia,” Anthony said. However, the drug can trigger pancreatitis, halting treatment and threatening the life of the patient.

“Currently, there are no established tools or clinical practices to predict the emergence of asparaginase-associated toxicities,” Anthony said.

Teaming with Loredana Quadro, a professor in the Department of Food Science at SEBS and a co-author of the study, they decided to search for any metabolic signatures that might exist and could be used to predict the onset of pancreatitis. In studies conducted at Rutgers, the scientists detected lower levels of vitamin A in the liver and the blood of mice exposed to asparaginase.

They combined their experimental data with other researchers’ analyses that included gene expression data in human patients administered asparaginase and electronic patient health records to understand more about the mechanisms driving the development of pancreatitis in some patients.

Collectively, the data showed that a lower level of dietary vitamin A is associated with an increased risk of developing pancreatitis, as well as an increase in its severity.

Vitamin A can be taken as a supplement or obtained through foods, including meat and dairy products as well as vegetables and fruits. It’s an essential nutrient for humans and aids general health, including vision, growth and cell division.

The researchers said the study could offer an important step forward in patient care and presents the opportunity for more research to examine how much vitamin A would be needed to protect every acute lymphocytic leukemia patient from pancreatitis.

“The long-term goal of this work is to make cancer treatment in children safer,” Quadro said.

Researchers from Stanford University and the University of Cincinnati College of Medicine also were involved in the study.