How I treat advanced phases of CML.

Advanced phases of Philadelphia chromosome-positive chronic myeloid leukemia (CML), classically encompassing de novo presentation of accelerated-phase disease and blast-phase disease (myeloid and lymphoid "blast crisis") and progression to these from antecedent chronic-phase disease, have diminished in incidence but remain a challenge. Despite continued development of additional and novel kinase inhibitors of BCR::ABL1, global limitations on access to diagnostics and therapy persist and account for continued incidence of advanced disease at initial presentation and progressive disease. Evolution in defining risk through clinical and molecular characterization should increase ability to identify emerging advanced disease, minimize progression, and improve treatment of resistant chronic-phase and blast-phase diseases. While BCR::ABL1 tyrosine kinase inhibition remains central in advanced disease, combination therapy with conventional and novel chemotherapy, immunotherapy, and allogeneic stem cell transplant provide best long-term outcomes.