A multi-center study on the consistency of drug sensitivity testing in patients with acute myeloid leukemia

Clinical implementation of patient cell-based drug testing is hampered by inconsistencies and irreproducible results. Using linear mixed models and drug response data from four cohorts of patients with acute myeloid leukemia (n = 993 samples), we identified sources of variability in ex vivo drug sensitivity testing across the studies. We identified several experimental factors, including the time until sample was tested, the type of culture media and viability assay, which led to systematic differences in drug sensitivity profiles. We further investigated the effects of sample types (fresh or frozen) and disease status (diagnosis, relapse, or refractory), and observed that peripheral blood samples resulted in higher drug sensitivity levels, compared to those derived from bone marrow. Technical factors, such as the type of plate reader and centrifugation procedure, further contributed to the response variability depending on the chosen drug response metric. These factors need to be standardized for improved consistency in functional precision medicine studies.