Understanding CML
Phases of Disease
Chronic myeloid leukaemia (CML) progresses through 3 distinct clinical phases:
- Chronic phase
- Accelerated phase
- Blast crisis (also called blast phase or blastic phase)
Chronic Phase of CML
At the time of initial diagnosis, the majority (over 80%) of patients with CML are in the chronic phase of disease.1
In the chronic phase of CML, signs and symptoms may be mild initially and worsen as the disease progresses.2 The most common symptoms at presentation in the chronic phase of CML include:3,4
- Fatigue
- Weight loss
- Abdominal fullness
- Bleeding
- Sweating
On physical examination, a palpable spleen is present in more than half of patients, although it is not unusual for patients to be asymptomatic at diagnosis.4
Laboratory Findings
The chronic phase of CML is defined by an elevated white blood cell count at presentation (≥20 × 109/L) and a relative lack of blasts (<10%) in peripheral blood and bone marrow (BM). Common laboratory findings include a complete blood cell count with differential analysis revealing:4,5
- Leukocytosis (≥20 × 109/L)
- Anaemia
- Thrombocytosis (in 30%-50% of patients)
- Thrombocytopaenia (especially in more advanced disease)
Overall risk of progression to advanced phase is low and is associated with the degree of response, regardless of when achieved. Five-year follow-up of 350 patients in the International Randomised Study of Interferon and STI571 (IRIS) trial who obtained a complete cytogenetic response at 12 months after initiation of Glivec treatment indicates that 97% of patients had not progressed to accelerated phase or blast crisis.6
Accelerated Phase of CML
The accelerated phase of CML is the second and intermediate phase in the natural history of the disease.2 Although diagnosis may be made on the basis of the presence of any of the typical laboratory findings, the defining criterion is the presence of 10%-19% blast cells in peripheral blood or BM.4,5 The onset of the accelerated phase may be marked by:3,5
- Thrombocytopaenia
- Progressive anaemia
As CML progresses through accelerated phase, a general worsening of symptoms occurs and additional symptoms may be observed, including:
- Bone pain
- Persistent unexplained fever
- Splenomegaly unresponsive to treatment
- Hepatomegaly
Blast Crisis: Final Phase of CML
The blast or blast-crisis phase is the final phase of CML; however, nearly 25% of patients progress directly from chronic phase to the terminal blast phase without evidence of transition through the accelerated phase18. Blast-crisis phase in CML may resemble acute leukaemia with increasing hypercellularity of the BM and a shift to more immature cells.4 The blast phase is characterised by the presence of >30% of blast cells in peripheral blood or BM.
This phase is marked by increased symptomatology, including:4
- Fatigue related to progressive anaemia
- Bleeding
- Infectious complications
- Lymphadenopathy
- Central nervous system (CNS) dysfunction
Overall, the prognosis for patients developing more advanced phases of CML is worse. Optimising the recognition of symptoms early in the course of CML disease is vital to increasing the chances for prolonged survival of patients with CML. Improvements in treatment options with the advent of the molecular era are redefining the course of CML disease.
References:
1. Cortes J. Natural history and staging of chronic myelogenous leukemia. Hematol Oncol Clin North Am. 2004;18:569-584.
2. Silver RT. Chronic myeloid leukemia. Hematol Oncol Clin North Am. 2003;17:1159-1173, vi-vii
3. Faderl S, Kantarjian HM, Talpaz M. Chronic myelogenous leukemia: update on biology and treatment. Oncology (Williston Park).1999;13:169-180; discussion 181, 184.
4. Kantarjian HM, Giles FJ, O'Brien SM, Talpaz M. Clinical course and therapy of chronic myelogenous leukemia with interferon-alpha and chemotherapy. Hematol Oncol Clin North Am. 1998;12:31-80.
5. Spiers AS. Clinical manifestations of chronic granulocytic leukemia. Semin Oncol. 1995;22:380-395.
6. Druker BJ, Guilhot F, O'Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408-2417.