Vitamin A and risk of pancreatitis during chemotherapy for ALL

By ASCO Postal Staff

Published: 03/17/2023 11:51:00

Last update: 03/17/2023 11:52:54

According to a recent study by Tsai et al in Science Translational Medicine.

Background

For patients with ALL, treatment with the enzyme asparaginase can help starve cancer cells by reducing the amount of asparagine circulating in the blood. However, an estimated 2% to 10% of patients on asparaginase therapy may experience pancreatitis as a side effect of treatment. In addition, a third of these patients may develop severe disease.

Study methods and results

In this study, researchers developed predictive analyzes using more than 100 million data points encompassing gene expression data, small molecule data, and electronic health records to better understand the mechanisms at the origin of asparaginase-associated pancreatitis and identify potential interventions to prevent or lessen the disease.

Researchers first analyzed gene expression data along with electronic health records and found that gene activity associated with asparaginase or pancreatitis could be reversed by retinoids, which include vitamin A and its analogues. The researchers further used the AERSExploit software, studied data from mouse models and compared plasma samples from patients with ALL who 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 to 3.4% of asparaginase-treated patients who did not consume vitamin A, 1.4% of those who consumed vitamin A developed pancreatitis. Researchers concluded that concurrent vitamin A use was correlated with a 60% reduction in the risk of asparaginase-associated pancreatitis, while lower amounts of dietary vitamin A were correlated with increased risk and severity. of the disease.

conclusion

“This study demonstrates the potential of mining ‘real world’ data to identify treatment modifiers to improve patient outcomes. In cases where a primary drug induces toxicity but is essential to treatment—[including] asparaginase – therapy modifiers such as vitamin A and its analogues may be of immediate relevance to patients on asparaginase and “at risk” for [asparaginase-associated pancreatitis]“, explained the co-lead author of the study Mayur Sarangdhar, PhD, MResAssistant Professor of Pediatrics in the Division of Biomedical Informatics at Cincinnati Children’s Hospital Medical Center.

“Our study highlights the power of integrating and analyzing heterogeneous data 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,” the study author emphasized. Anil Gold Jegga, DMV, MResProfessor of Pediatrics in the Division of Biomedical Informatics at Cincinnati Children’s Hospital Medical Center.

The researchers concluded that their findings could be applied to patient care. However, further clinical research is needed to determine how much vitamin A is needed to protect patients with ALL from developing pancreatitis and whether a level of protection can be achieved through diet or via supplements.

Disclosure: For full disclosures from the study authors, visit science.org.

The content of this article has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the views and opinions of ASCO®.

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