Synergy of anti-leukemic effects between anti-thymocyte globulin, busulfan, and fludarabine

Date
2017-11-30
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Abstract
Antithymocyte Globulin (ATG) is an anti-GvHD (Graft versus Host Disease) drug that has recently been shown to have anti-leukemic effects. In Alberta, Busulfan and Fludarabine are used to treat acute myeloid leukemia. However, both drugs also lead to the death of healthy cells within the body, especially with increased doses. It would be beneficial to study ways to maintain their effects while decreasing their toxicity, such as synergy with ATG. Different concentrations of ATG were combined with different concentrations of Busulfan and Fludarabine separately to test their effects on pre-conditioned leukemia cell samples from acute myeloid leukemia patients. Cell death was quantified using flow cytometry. The cells from five patients were used and combined into graphs that compared cells dyed by 7AAD (dead cells) between the drugs. In some of the combinations, there appeared to be increased cell death in test tubes with a combination of ATG with Busulfan or ATG with Fludarabine. However, with the use of the Wilcoxon Matched Pairs Test, the difference was deemed not significant. Even though there were no significant differences, it could be due to the low sample size. Furthermore, other concentrations not tested in this experiment could yield better results. If synergy exists between ATG and Busulfan or Fludarabine, the two drugs should be moved up in patients’ conditioning schedules to allow synergism to occur, leading to more cancer cell death with less risk for side effects.
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Keywords
Leukemia, Cancer, Immunology, Pharmacology, Busulfan, Fludarabine, Anti-Thymocyte Globulin
Citation
Yang, L. (2017). "Synergy of anti-leukemic effects between anti-thymocyte globulin, busulfan, and fludarabine". 12th Annual Students' Union Undergraduate Research Symposium, November 30, 2017. University of Calgary, Calgary, AB.