A new study shows that a diet high in vitamin A or its analogues could help adolescents and young adults with acute lymphoblastic leukemia (ALL) reduce their risk of painful inflammation of the pancreas during chemotherapy.
Details of 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 Husain, 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.
In people with ALL, treatment with the enzyme asparaginase helps starve cancer cells by reducing the amount of asparagine circulating in the blood, which the cancer cells need but cannot make themselves. The drug, which is often used in combination with other chemotherapy treatments, is given by injection into a vein, muscle or under the skin, according to the study.
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However, an estimated 2% to 10% of asparaginase users develop inflammation of the pancreas in response to treatment with asparaginase. In a third of these people, symptoms can be severe.
Jegga and colleagues developed predictive analytics using over 100 million data points spanning gene expression data, small molecule data and electronic health records to understand more about the mechanisms driving asparaginase-associated pancreatitis (AAP) and potential interventions to prevent or mitigate AAP to identify.
First, they analyzed vast amounts of gene expression data to show that gene activity associated with asparaginase or pancreatitis could be reversed by retinoids (vitamin A and its analogues). The team found further supporting evidence by “scrutinizing” millions of electronic medical records from the US Federal Drug Administration’s TriNetX database and adverse event 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 looked at data from mouse experiments, comparing plasma samples from people with ALL who developed pancreatitis and those who didn’t.
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 also took vitamin A, compared to 3.4% of patients who did not. Concomitant use of vitamin A correlated with a 60% reduction in AAP risk.
Lower amounts of dietary vitamin A correlated with increased risk and severity of AAP.
“This study demonstrates the potential of extracting ‘real-world’ data to identify therapy modifiers to improve patient outcomes. Analogues may be of immediate relevance to asparaginase patients and patients ‘at risk’ for AAP,” says Sarangdhar, co-author of the study .
Says Jegga: “Our study underscores the power of heterogeneous data integration and analysis in translational research. By leveraging existing omics and patient-centric data and a systems approach, we were able to gain new insights into the development of AAP and possible interventions to prevent or mitigate this side effect.”
Next Steps
In a way, the insights from this study could be directly applied to patient care. However, more clinical research is needed to determine how much vitamin A would be required to protect ALL patients from pancreatitis; and whether a level of protection can be achieved through diet or supplements. In fact, target vitamin levels may need to vary based on individual differences in metabolism.
This story was published from a wire agency feed with no changes to the text. Only the headline has been changed.
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