Cincinnati [US], March 19 : A diet high in vitamin A or its analogues may help prevent children and young adults with acute lymphoblastic leukaemia (ALL) from developing painful pancreas inflammation during chemotherapy.
Details about this potential dietary solution to prevent a potentially life-threatening adverse event were published in Science Translational Medicine. The research team was led by Sohail Husain, MD, chief of Pediatric Gastroenterology, Hepatology, and Nutrition at Stanford University and l Goud Jegga, DVM, MRes, a computational biologist at Cincinnati Children's Hospital Medical Center.
For 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 medication, often used in combination with other chemotherapies, is given via injection into a vein, muscle, or under the skin.
However, an estimated 2 per cent to 10 per cent of asparaginase users develop inflammation of the pancreas in reaction to asparaginase treatment. For a third of these people, the symptoms can be severe.
Jegga and colleagues developed predictive analytics using over 100 million data points encompassing gene expression data, small-molecule data, and electronic health records to understand more of the mechsms driving asparaginase-associated pancreatitis (AAP) and identify potential interventions to prevent or mitigate AAP.
First, they analyzed massive amounts of gene expression data to reveal that gene activity associated with asparaginase or pancreatitis might be reversed by retinoids (vitamin A and its analogues). The team found more supporting evidence by "mining" millions of electronic health records from the TriNetX database and the U.S. Federal Drug Administration Adverse Events Reporting System.
This number crunching and predictive analytics work included the use of the AERSMine software developed at Cincinnati Children's by Mayur Sarangdhar, PhD, MRes, and colleagues. The research team also studied data from mice experiments and compared plasma samples from people with ALL 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 per cent of patients treated with asparaginase developed pancreatitis when they were also taking vitamin A in contrast to 3.4 per cent of patients who did not. Concomitant use of vitamin A correlated with a 60 per cent reduction in the risk of AAP. Lower amounts of dietary vitamin A correlated with increased risk and severity of AAP.
"This study demonstrates the potential of mining 'real-world' data to identify therapy modifiers for improving patient outcomes. In cases where a primary drug induces toxicity but is critical to therapy, such as asparaginase, therapy modifiers, such as vitamin A and its analogues, may be of immediate relevance to patients on asparaginase and 'at-risk' for AAP," says Sarangdhar, a co-first author of the study.
Says Jegga: "Our study highlights 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 identify new insights into the development of AAP and potential interventions to prevent or mitigate this side effect."
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