Browsing by Subject "drug sensitivity testing"

Ex vivo drug sensitivity testing is used widely in studies aiming at personalizing medicine for acute myeloid leukemia (AML) patients. However, different conditions, such as cytokines used in media and cryopreservation of cells, as well as varying readout methods can affect primary cell viability, cell composition and sensitivity results. Such affects have been previously studied in some AML treatments, however, not with flow cytometry or with venetoclax. In this thesis, we studied the responses of AML patients to venetoclax using ex vivo drug sensitivity testing with various settings. We first tested three media and two sensitivity readout methods on 29 fresh primary AML samples to determine the optimal media and method for determining ex vivo drug sensitivity. We then tested these same variables on 16 cryopreserved samples and compared these results to their fresh counterparts. Finally, we applied our platform to clinical use and tested its capability to predict in vivo responses to venetoclax in ten AML patients. Our platform was able to predict venetoclax responses in nine out of ten patients using condition media coupled with a flow cytometry-based method, determined as optimal in the first phase. Sensitivity results as well as cell composition obtained after cryopreservation differed from their fresh counterparts and, therefore, we conclude that cryopreserved samples should not be used in guiding treatment ex vivo. Our results give valuable information about sources of error associated with ex vivo drug sensitivity testing. Consideration of these results when designing preclinical studies will enhance their reliability and relevance. Ex vivo testing could be in the future implemented into clinical practice in guiding treatment, saving society and patients from costs and unnecessary adverse effects.