Chronic myelogenous leukemia classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2]

Overview

Chronic myelogenous leukemia may be classified according to the clinical characteristics and laboratory findings into three subtypes: chronic phase, accelerated phase, and blast crisis.

Phases of CML

CML is often divided into three phases based on clinical characteristics and laboratory findings.

Phases	Associations
Chronic phase	Most patients are diagnosed in this phase Less than 10% of cells in the blood and bone marrow are blasts Usually asymptomatic or mild symptoms my present Progress slowly Respond well to treatment
Accelerated phase	10-20% of cells in the blood and bone marrow are blasts Cells show more damage to their DNA and grow faster Cells have often developed new changes in addition to the Philadelphia chromosome Usually symptomatic Poor response to treatment
Blast or acute phase	Disease acts more like an acute leukemia 30% of cells in blood and bone marrow are blast Blast cells often spread to tissues and organs outside the bone marrow Blast crisis may occur The accelerated phase can change quickly into the blast phase with symptoms of fever, malaise and splenomegaly Usually symptomatic Bleeding and infections are common

CML is often divided into three phases based on clinical characteristics and laboratory findings. In the absence of intervention, CML typically begins in the chronic phase, and over the course of several years progresses to an accelerated phase and ultimately to a blast crisis. Blast crisis is the terminal phase of CML and clinically behaves like an acute leukemia. One of the drivers of the progression from chronic phase through acceleration and blast crisis is the acquisition of new chromosomal abnormalities (in addition to the Philadelphia chromosome). Some patients may already be in the accelerated phase or blast crisis by the time they are diagnosed.

Chronic phase

Approximately 85% of patients with CML are in the chronic phase at the time of diagnosis. During this phase, patients are usually asymptomatic or have only mild symptoms of fatigue or abdominal fullness. The duration of chronic phase is variable and depends on how early the disease was diagnosed as well as the therapies used. Ultimately, in the absence of curative treatment, the disease progresses to an accelerated phase.

Accelerated phase

Criteria for diagnosing transition into the accelerated phase are somewhat variable; the most widely used criteria are those put forward by investigators at M.D. Anderson Cancer Center, by Sokal et al, and the World Health Organization. The WHO criteria are perhaps most widely used, and include:

• 10–19% myeloblasts in the blood or bone marrow
• >20% basophils in the blood or bone marrow
• Platelet count <100,000, unrelated to therapy
• Platelet count >1,000,000, unresponsive to therapy
• Cytogenetic evolution with new abnormalities in addition to the Philadelphia chromosome
• Increasing splenomegaly or white blood cell count, unresponsive to therapy

The patient is considered to be in the accelerated phase if any of the above are present. The accelerated phase is significant because it signals that the disease is progressing and transformation to blast crisis is imminent.

Blast crisis

Blast crisis is the final phase in the evolution of CML, and behaves like an acute leukemia, with rapid progression and short survival. Blast crisis is diagnosed if any of the following are present in a patient with CML:

• >20% myeloblasts or lymphoblasts in the blood or bone marrow
• Large clusters of blasts in the bone marrow on biopsy
• Development of a chloroma (solid focus of leukemia outside the bone marrow)

References

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