Eating a diet rich in vitamin A or its analogues may help prevent children and young adults with acute lymphoblastic leukemia (ALL) by reducing the risk of developing painful pancreatitis during chemotherapy.
For people with ALL, treatment with the enzyme asparaginase helps starve cancer cells by reducing the amount of asparagine circulating in the blood, which 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.
However, an estimated 2% to 10% of asparaginase users develop pancreatitis as a reaction to asparaginase treatment. For a third of these people, symptoms can be severe.
Jegga and colleagues developed predictive analyzes using more than 100 million data points including gene expression data, small molecule data and electronic health records to further understand the mechanisms driving asparaginase-associated pancreatitis (AAP) and to 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 could 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 US Federal Drug Administration’s adverse event reporting system.
Number crunching and predictive analytics work involved the use of AERSroyal A program developed at Cincinnati Children’s by Mayur Sarangdhar, Ph.D., MRes, and colleagues. The research team also studied data from mouse experiments and compared plasma samples from people with ALL who developed pancreatitis and those who did not.
In the end, the team created two sets of human “real world” experiments. They found that only 1.4% of patients treated with asparaginase developed pancreatitis when they were also taking vitamin A, in contrast to 3.4% of patients who did not take it. Concurrent use of vitamin A is associated with a 60% lower risk of AAP. Low amounts of dietary vitamin A have been associated with an increased risk and severity of AAP.
“This study demonstrates the potential for ‘real-world’ data mining to determine treatment rates to improve patient outcomes. In cases where a prodrug causes toxicity but is essential for treatment, such as asparaginase, treatment rates, such as vitamin A and its analogues, may be relevant. directly to patients taking asparaginase and “at risk of developing AAP,” says Sarangdhar, co-first author of the study.
“Our study highlights the power of integrating and analyzing heterogeneous data in translational research,” says Giga. “By leveraging existing data omics with a patient-centered and systems approach, we were able to identify novel insights into the development of AAP and potential interventions in order to prevent or mitigate this side effect.” “.
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 determine how much vitamin a is needed to protect all patients from pancreatitis; and whether the level of protection can be achieved by diet or by supplementation. In fact, target vitamin levels may need to vary according to individual differences in metabolism.