Phenotypic Drug Response Profiling Identifies Asparaginase-Based Synergistic Combinations for Very High Risk Acute Lymphoblastic Leukaemia

In acute lymphoblastic leukaemia (ALL), empirical multi-drug chemotherapy combinations lead to >85% cure rates in children. But 10-15% of patients show suboptimal response and as drugs are dosed to tolerance, further intensification is not possible. An exception is the key antileukaemic drug, asparaginase (ASNase), which is not associated with dose-related toxicity. We evaluated the use of ex-vivo co-culture based drug response profiling (DRP) to identify novel synergistic and effective drug combinations with ASNase for patients with suboptimal responses to standard chemotherapy in ALL.