Consuming a diet rich in vitamin A or its analogs may help prevent pediatric and young adult patients with acute lymphoblastic leukemia (ALL) reduce their risk of developing pancreatitis during chemotherapy, according to a recent study by Tsai et al in Science Translational Medicine.
Background
For patients with ALL, treatment with the enzyme asparaginase may help starve cancer cells by reducing the amount of asparagine circulating in the blood. However, an estimated 2% to 10% of patients who undergo treatment with asparaginase may experience pancreatitis as a side effect to the treatment. Further, one-third of these patients may develop severe disease.
Study Methods and Results
In this study, the researchers developed predictive analytics using more than 100 million data points encompassing gene-expression data, small-molecule data, and electronic health records to more fully understand the mechanisms driving asparaginase-associated pancreatitis—and identify potential interventions to prevent or mitigate the disease.
The researchers first analyzed the gene-expression data as well as electronic health records and found that gene activity associated with asparaginase or pancreatitis might be reversed by retinoids—which include vitamin A and its analogs. The researchers further utilized the AERSMine software, studied data from mouse models, and compared plasma samples from patients who had ALL and developed pancreatitis with those who had ALL but did not develop the disease.
After conducting their analysis, the researchers developed two sets of real-world human experiences. They found that compared with 3.4% of patients treated with asparaginase who did not consume vitamin A, 1.4% of those who did consume vitamin A developed pancreatitis. The researchers concluded that concomitant use of vitamin A correlated with a 60% reduction in the risk of asparaginase-associated pancreatitis, whereas lower amounts of dietary vitamin A correlated with an increased risk and severity of the disease.
Conclusions
“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—[including] asparaginase—therapy modifiers such as vitamin A and its analogs may be of immediate relevance to patients on asparaginase and ‘at-risk’ for [asparaginase-associated pancreatitis],” explained co–lead study author Mayur Sarangdhar, PhD, MRes, Assistant Professor of Pediatrics in the Division of Biomedical Informatics at the Cincinnati Children’s Hospital Medical Center.
“Our study highlights the power of heterogeneous data integration and analysis in translational research. By leveraging existing ‘omics, patient-centric data, and a systems approach, we were able to identify new insights into the development of [asparaginase-associated pancreatitis] and potential interventions to prevent or mitigate this side effect,” underscored study author Anil Goud Jegga, DVM, MRes, Professor of Pediatrics in the Division of Biomedical Informatics at the Cincinnati Children’s Hospital Medical Center.
The researchers concluded that their findings could be applied to patient care. However, more clinical research is needed to establish how much vitamin A would be needed to protect patients with ALL from developing pancreatitis—and whether a protective level can be achieved by diet or via supplements.
Disclosure: For full disclosures of the study authors, visit science.org.
