Progression

Typically CML follows three identifiable phases (triphasic):

• chronic phase (CP):
  • more than 90% of patients are diagnosed at this phase (1)
  • duration is variable, median of 3 years, range of several months to more than 10 years
  • treatment can alleviate symptoms and return the white cell count and spleen to normal
  • few symptoms
• accelerated disease (AP):
  • two-thirds gradually transform to an acute leukaemia, this is termed the accelerated phase
  • lasts for 2–15 months after which blast crisis phase occurs (2)
  • characterised by an increasing arrest of maturation (which is an indication of transformation to BP)
  • WHO criteria used to define this phase
    • blasts 10%-19% of WBCs in peripheral and/or nucleated bone marrow cells
    • peripheral blood basophils 20%
    • persistent thrombocytopenia (< 100 x 10 /L) unrelated to therapy, or persistent thrombocytosis (> 1000 x 10 /L) unresponsive to therapy
    • increasing spleen size and increasing WBC count unresponsive to therapy
    • cytogenetic evidence of clonal evolution
• blastic phase (BP) or blast crisis (BC)
  • lasts 3-6 months and inevitably leads to death (2)
  • around 20-25% of patients progress directly from CP to BP (3)
  • WHO definition criteria of this phase
    • blasts 20% of peripheral blood white cells or nucleated bone marrow cells
    • extramedullary blast proliferation
    • large foci or clusters of blasts in the bone marrow biopsy

Gradual progression of AML from chronic phase through accelerated phase to blastic phase may take around 1 year or more (4).

• typically, the annual progression from chronic to blast-crisis phase is 5-10% in the first 2 years, and 20% in subsequent years (2).

The transformed disease resembles a fulminating acute leukaemia. 70% of cases involve myeloid lineage blast cells. Lymphoid blast cells are less common and display characteristic cell membrane markers such as common acute lymphoblastic leukaemia antigen (CALLA), and nuclear terminal deoxynucleotidyl transferase.

Reference:

• (1) Baccarani M et al. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v165-7.
• (2) NICE (October 2003).Guidance on the use of imatinib for chronic myeloid leukaemia
• (3) Jabbour E et al. Current and emerging treatment options in chronic myeloid leukemia. Cancer. 2007;109(11):2171-81.
• (4) National Cancer Institute at the National Institutes of Health. Chronic Myelogenous Leukemia Treatment