Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder. The disease is driven by the BCR-ABL1 chimeric gene product, that codes for a constitutively active tyrosine kinase, resulting from a reciprocal balanced translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34.1;q11.2), known as the Philadelphia chromosome (Ph) (Fig. 101-1). Untreated, the course of CML is typically biphasic or triphasic, with an early indolent or chronic phase, followed often by an accelerated phase and a terminal blastic phase. Before the era of selective BCR-ABL1 tyrosine kinase inhibitors (TKIs), the median survival in CML was 3–7 years, and the 10-year survival rate was 30% or less. Introduced into standard CML therapy in 2000, TKIs have revolutionized the treatment, natural history, and prognosis of CML. Today, the estimated 10-year survival rate with imatinib mesylate, the first BCR-ABL1 TKI approved, is 85%. Allogeneic stem cell transplantation (SCT), a curative approach but one that involves more risks, is now more often offered as second- or third-line therapy after failure of TKIs.
A. The Philadelphia (Ph) chromosome cytogenetic abnormality. B. Breakpoints in the long arms of chromosome 9 (ABL locus) and chromosome 22 (BCR regions) result in at least three different BCR-ABL1 oncoprotein messages, p210BCR-ABL1 (most common message in chronic myeloid leukemia [CML]), p190BCR-ABL1 (present in two-thirds of patients with Ph-positive acute lymphocytic leukemia; rare in CML), and p230BCR-ABL1 (rare in CML and associated with an indolent course). Other rearrangements (e.g., b14a3) are less common. (© 2013 The University of Texas MD Anderson Cancer Center.)
INCIDENCE AND EPIDEMIOLOGY
CML accounts for ∼15% of all cases of leukemia. There is a slight male preponderance (male:female ratio 1.6:1). The median age at diagnosis is 55–65 years. It is uncommon in children; only 3% of patients with CML are younger than 20 years although in recent years a higher proportion of young patients seem to be diagnosed. CML incidence increases slowly with age, with a steeper increase after the age of 40–50 years. The annual incidence of CML is 1.5 cases per 100,000 individuals. In the United States this translates into about 8000 new cases per year. The incidence of CML has not changed over several decades. By extrapolation, the worldwide annual incidence of CML is about 100,000–120,000 cases. With a median survival of 6 years before 2000, the disease prevalence in the United States was 25,000–30,000 cases. With TKI therapy, the annual mortality has been reduced from 10–20% to about 2%. Therefore, the prevalence of CML in the United States is expected to continue to increase (approximately 100,000 in 2016). The worldwide prevalence will depend on the treatment penetration of TKIs and their effect on reduction of worldwide annual mortality. Ideally, ...