Advanced-Stage Chronic Myeloid Leukemia: Options for Difficult Treatment Situations

A small number of patients with chronic myeloid leukemia (CML) either present with or progress to the accelerated phase (AP) or blast phase (BP). This occurs in approximately 4–7% of patients with CML. Most patients who progress to BP-CML are of myeloid lineage, while approximately 30% are of lymphoid lineage. Due to the rarity of this condition, there are no large or randomized trials that can inform clinical decisions. Most data are from retrospective chart reviews or data from old studies when tyrosine kinase inhibitors (TKIs) were initially approved. In addition, the definition of these categories has been in continuous flux over the last 20 years, making applicability of data even more confusing. In some classifications, the cutoff is 30% blasts for the definition of BP-CML, while in others a cutoff of 20% is used. In addition, more recently the World Health Organization (WHO) classification omitted the accelerated phase and recognized only a two-phase disease, while the International Consensus Classification retained a three-phase definition and retained the accelerated phase. Therapy for patients with AP/BP-CML depends on several factors, including prior therapy, BCR::ABL1 mutation, co-morbidities, cell lineage, and eligibility for allogeneic stem cell transplantation (alloHCT). Patients with AP-CML at presentation have a relatively favorable prognosis and may not need alloHCT if they respond appropriately to therapy. For patients with AP-CML who progressed while on TKI therapy or those with BP-CML, alloHCT is considered the only curative therapy. Our goal is to review the available data on the therapy of patients with AP-CML and BP-CML.