Blast and accelerated phase CML: room for improvement

Abstract

Tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). With TKI therapy, the percentage of patients who progress to accelerated phase (AP) or blast phase (BP) CML has decreased from more than 20% to 1% to 1.5% per year. Although AP- and BP-CML occur in a minority of patients, outcomes in these patients are significantly worse compared with chronic phase CML, with decreased response rates and duration of response to TKI. Despite this, TKIs have improved outcomes in advanced phase CML, particularly in de novo AP patients, but are often inadequate for lasting remissions. The goal of initial therapy in advanced CML is a return to a chronic phase followed by consideration for bone marrow transplantation. The addition of induction chemotherapy with TKI is often necessary for achievement of a second chronic phase. Given the small population of patients with advanced CML, development of novel treatment strategies and investigational agents is challenging, although clinical trial participation is encouraged in AP and BP patients, whenever possible. We review the overall management approach to advanced CML, including TKI selection, combination therapy, consideration of transplant, and novel agents.

Use of low-dose decitabine with or without tyrosine kinase inhibitors in advanced phase chronic myelogenous leukemia: a systemic review and metaanalysis

“…Response ranges from 11% to 57%, with survival rate ranging from 60% at 4 years for Bosutinib to 84% at 1 year for Ponatinib. 12 These responses were also reflected in an earlier study done by Bonifacio et al…”

“…Response ranges from 11% to 57%, with survival rate ranging from 60% at 4 years for Bosutinib to 84% at 1 year for Ponatinib. 12 These responses were also reflected in an earlier study done by Bonifacio et al (2019). 13 However, other treatment modalities, like chemotherapy, and if possible, hematopoietic stem cell transplantation (HSCT), are generally recommended in advanced phase CML, especially in blastic phase.…”

“…These regimens produced a superior survival rates compared to TKI alone. 12 Based on one of the mechanisms of disease progression in CML, decitabine has been explored even in the pre-TKI era, to address hypermethylation seen in advanced phase CML. 3 In an earlier study by Kantarjian et al (1997), 37 patients with advanced phase CML were treated with 75 to 100 mg/m 2 decitabine for 10 doses.…”

Identification of microRNA editing sites in three subtypes of leukemia

“…In most cases, this disease involves a bone marrow malignancy, although malignant cells may also be detected in peripheral blood or as extramedullary infiltration ( Doehner et al, 2013 ; Nepstad et al, 2020 ). CML is a myeloproliferative neoplasm characterized by the Philadelphia chromosome (Ph) that affects one to two per 100,000 new patients per year and comprises 15% of leukemias in adults ( How et al, 2021 ). The disease is driven by a reciprocal translocation of chromosomes 9 and 22, which results in the BCR-ABL fusion protein and dysregulated tyrosine kinase activity ( Shallis et al, 2020 ).…”

Differences In Hematology And Bcr-Abl Molecular Profiles In Patients With Chronic Myeloid Leukemia Undergoing Tyrosine Kinase Inhibitor Therapy

“…However, unless proper treatment is administered, the disease can progress to an accelerated phase to a blast crisis phase within 3-5 years (Brümmendorf et al, 2020). The chronic phase is usually asymptomatic, yet in the accelerated phase and the blast crisis phase, the symptoms will become more severe as characterized by anemia and a platelet count below 100,000/mm3 or above 1,000,000/mm3 (How et al, 2021).…”