A new study shows that a diet high in vitamin A or its analogs may help reduce the risk of painful pancreatic inflammation during acute lymphoblastic leukemia (ALL) chemotherapy in adolescents and young adults.
Details about this potential dietary solution to prevent a potentially life-threatening adverse event were published March 15 in Science Translational Medicine. The research team was led by Sohail Hussain, MD, of Stanford University’s Department of Pediatric Gastroenterology, Hepatology and Nutrition, and computational biologist Anil Goud Jegga, DVM, MRS, of Cincinnati Children’s Hospital Medical Center.
For people with ALL, treatment with the enzyme asparaginase helps starve cancer cells by reducing the amount of circulating asparagine in the blood, which cancer cells need but cannot make themselves. The drug, often used in combination with other chemotherapy, is given through a vein, muscle or injection under the skin, the study said.
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However, an estimated 2% to 10% of asparaginase users develop inflammation of the pancreas in response to asparaginase treatment. For one-third of these people, symptoms can be severe.
Jegga and colleagues predicted using 100 million data points including gene expression data, small-molecule data, and electronic health records to understand additional mechanisms driving asparaginase-associated pancreatitis (AAP) and identify potential interventions to prevent or reduce AAP. developed the analyses.
First, they analyzed large amounts of gene expression data to reveal that gene activity associated with asparaginase or pancreatitis could be reversed by retinoids (vitamin A and its analogs). The team found additional supporting evidence by “mining” millions of electronic health records from the TriNetX database and the US Federal Drug Administration Adverse Event Reporting System.
This number crunching and predictive analytics work involved the use of AERSmine software developed at Cincinnati Children’s by Mayur Sarangdhar, PhD, MRS, and colleagues. The research team also studied data from mice and compared plasma samples from those with and without pancreatitis.
Ultimately, the team established two sets of human “real-world” experiences. They found that only 1.4% of patients treated with asparaginase developed pancreatitis when they were also taking vitamin A compared to 3.4% of patients who did not. Concomitant use of vitamin A is associated with a 60% reduction in the risk of AAP.
Low intake of dietary vitamin A is associated with increased risk and severity of AAP.
“This study demonstrates the potential of mining ‘real-world’ data to identify therapy modifiers to improve patient outcomes. Primary drugs that cause toxicity but are important for therapy, such as asparaginase, therapy modifiers, such as vitamin A and its analogs, are of immediate relevance to patients with asparaginase. may and may be ‘at risk’ for AAP,” says Sarangdhar, co-first author of the study.
Jegga says: “Our study highlights the power of heterogeneous data integration and analysis in translational research. By leveraging existing ‘omics and patient-centered data and systems approaches, we were able to identify new insights into AAP and the development of potential interventions. To prevent or reduce this side effect Do it.”
Next steps
In some ways, the lessons learned from this study can be immediately applied to patient care. However, more clinical research is needed to establish how much vitamin A is needed to protect all patients from pancreatitis; And a protective level can be achieved through diet or supplementation. In fact, target vitamin levels may vary according to individual differences in metabolism.
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