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Chronic Myeloid Leukaemia - CML Symptoms
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CML symptoms during the Chronic Phase of CML
CML symptoms during the Accelerated Phase of CML
CML symptoms during the Blast Crisis: Final Phase of CML
Chronic myeloid leukaemia (CML) progresses through 3 distinct clinical phases:
- Chronic phase
- Accelerated phase
- Blast crisis (also called blast phase or blastic phase)
CML symptoms during the Chronic Phase of CML
At the time of initial diagnosis, the majority (over 80%) of patients with CML are in the chronic phase of disease15. In the chronic phase, the signs and symptoms of CML may be mild initially and worsen as the disease progresses20. The most common CML symptoms at presentation in the chronic phase include17, 18:
- 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 diagnosis18.
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)20. Common laboratory findings include a complete blood cell count with differential analysis revealing18, 19:
- 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 crisis6.
CML symptoms during the Accelerated Phase of CML
The accelerated phase of CML is the second and intermediate phase in the natural history of the disease20. 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 BM18,19. The onset of the accelerated phase may be marked by17,19:
- Thrombocytopaenia
- Progressive anaemia
As CML progresses through accelerated phase, a general worsening of CML symptoms occurs and additional symptoms may be observed, including18:
- Bone pain
- Persistent unexplained fever
- Splenomegaly unresponsive to treatment
- Hepatomegaly
CML symptoms during the 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 cells18. The blast phase is characterised by the presence of >30% of blast cells in peripheral blood or BM.
This phase is marked by an increase in the CML symptoms, including18:
- 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 the 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.
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