A new study suggests that a diet high in vitamin A or its equivalent may help adolescents and young adults with acute lymphoblastic leukemia (ALL) reduce their risk of painful pancreatic inflammation during chemotherapy.
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, chief of pediatric gastroenterology, hepatology and nutrition at Stanford University, and Anil Goud Jegga, DVM, MRes, a computational biologist at Cincinnati Children’s Hospital Medical Center.
For people with ALL, treatment with the enzyme asparagine helps starve cancer cells by reducing the amount of asparagine circulating in the blood, which cancer cells need but cannot make themselves. The drug, often used in combination with other chemotherapies, is given through injection into a vein, muscle or under the skin, the study said.
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However, an estimated 2% to 10% of asparagus users develop inflammation of the pancreas in response to asparagus treatment. Symptoms can be severe in up to a third of these people.
Jegga and colleagues developed predictive analysis using more than 100 million data points incorporating gene expression data, small-molecule data and electronic health records to better understand the mechanisms driving asparagus-associated pancreatitis (AAP). and identify potential interventions to prevent or reduce AAP.
First, they analyzed massive amounts of gene expression data to reveal that gene activity associated with asparagine or pancreatitis could be reversed by retinoids (vitamin A and its analogs). The team found more supporting evidence by “mining” millions of electronic health records from the TriNetX database and the US Federal Drug Administration Adverse Events Reporting System.
This number crunching and predictive analytics work involved the use of AERSMine software developed by Mayur Sarangdhar, PhD, MRes, and colleagues at Cincinnati Children’s. The research team also studied data from experiments with mice and compared plasma samples from everyone who developed pancreatitis and those who did not.
Ultimately, the team established two sets of human “real world” experiences. They found that only 1.4% of patients treated with asparagus developed pancreatitis when they were also taking vitamin A, as opposed to 3.4% of patients who were not. Vitamin A use correlated with a 60% reduction in the risk of AAP.
Low intake of dietary vitamin A is related to increased risk and severity of AAP.
“This study demonstrates the potential of ‘real-world’ data mining to identify therapy modifiers to improve patient outcomes. In cases where the primary drug induces toxicity but is critical to treatment, such as asparagus, Therapy modifiers, such as vitamin A and its analogs for asparaginase and AAP, “may be of immediate relevance to patients at ‘at-risk’,” 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-centred data and a systems approach, we hope to gain new insights into the development of AAP and potential interventions.” were able to identify. prevent or reduce this side effect.”
next steps
In some ways, the learnings from this study can be immediately applied to patient care. However, more clinical research is needed to establish what dose of vitamin A would be needed to protect all patients from pancreatitis. and whether a protective level can be achieved through diet or supplementation. In fact, target vitamin levels may need to be varied according to individual differences in metabolism.
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