Nicholas Short, MD, University of Texas MD Anderson Cancer Center, Houston, TX, outlines what questions need to be addressed to make the best use of the therapeutic armamentarium of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Dr Short believes that the drugs currently available can lead to cure in most patients. However, how to combine them remains an open question. The frontline use of more potent tyrosine kinase inhibitors and blinatumomab should be considered rather than waiting for the relapsed/refractory setting. Additionally, deep curative therapies without the need for transplant are yet to see. This interview took place during the 2021 European School of Hematology (ESH) 2nd Translational Research Conference on Acute Lymphoblastic Leukemia.