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There are currently several novel therapies being explored for the treatment of patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL), particularly in the relapsed/refractory setting. Adoptive cell therapies that engineer T cells to attack the tumor are of extreme interest. These approaches use a variety of methods that train T cells to recognize leukemia and B cells that express a specific protein. Three types of therapies have shown promise as treatments for ALL: CAR-modified T cells, the antibody blinatumomab, and the antibody-drug conjugate SGN-19A.