Chronic Myeloid Leukemia Diagnosis and Staging

April 19, 2024 
This page was reviewed under our medical and editorial policy by Guido Marcucci, M.D., Chair, Department of Hematologic Malignancies Translational Science, City of Hope Duarte

Chronic myeloid leukemia, or CML, is a type of blood cancer that’s diagnosed using a variety of tests. Since CML symptoms aren’t always present, the first indication of the disease is often high white blood cell counts found during routine blood tests, such as during a yearly examination.

A high white blood cell count may also indicate other conditions besides CML, and that’s why a doctor will order additional blood, bone marrow and genetic tests before making a diagnosis. A doctor called a pathologist then analyzes and interprets these test results.

Once a diagnosis is made, a patient’s care team focuses on identifying the cancer’s phase to understand how far it has spread, the recommended treatment plan and the outlook for recovery. A patient’s care team may include doctors such as a hematologist, who has expertise with blood disorders, and an oncologist, who provides cancer medicine like chemotherapy and radiation therapy.

How Is CML Diagnosed?

Three main types of tests are used to provide the most accurate chronic myeloid leukemia diagnosis.

Blood Cell Counts

Patients with CML have high levels of white blood cells, and they may also have low red blood cell counts and either high or low platelet levels. A CBC, or complete blood count, is used to measure these cell components. 

The shape and size of the white blood cells in the CBC are also analyzed using a test known as a blood smear. Doctors look for features that indicate these cells are immature. A high number of a specific type of immature white blood cell called a myeloblast or blast is an indication that a person has CML.

Genetic Tests

Almost all people with CML have the Philadelphia chromosome, which is a genetic mutation that forms after birth mainly due to DNA damage. Cytogenetic tests are designed to check for this chromosome and the genes that form it, called ABL1 and BCR.

During cytogenetics testing, bone marrow and sometimes blood samples are analyzed under a microscope to determine if the Philadelphia chromosome is present.

Sometimes, the Philadelphia chromosome is unable to be located, and technicians instead look for the genes that form the chromosome using more sensitive tests, such as the FISH (fluorescence in situ hybridization) or the PCR (polymerase chain reaction) DNA test.

Bone Marrow Tests

Knowing the ratio of blood-forming cells to fat-forming cells in bone marrow may aid pathologists in diagnosing CML. This is because people with the condition may have hypercellular bone marrow, which is a higher-than-normal number of blood-forming cells.

The two types of bone marrow tests that may be used to look for hypercellularity and other indicators of CML are listed below.

Bone marrow aspiration: A doctor uses a thin needle with suction to take a sample of fluid containing bone marrow cells, usually from the hip, but sometimes from the breastbone.

Bone marrow biopsy: A doctor employs a larger needle to remove a piece of the marrow from the same location. This is usually performed alongside an aspiration.

Bone marrow aspiration and biopsy tests are typically outpatient procedures that may be done in the doctor’s office with local anesthesia.

Additional tests aim to help clinicians and doctors expand the cancer care team’s understanding of CML cancer and how it affects the person’s tissues and organs. These may include:

• Blood chemistry tests that check for kidney or liver problems caused by CML spreading
• Imaging tests such as a computed tomography (CT) scan, magnetic resonance imaging (MRI) and ultrasound to look for symptom causes, cancer spread and the effects of CML cancer, such as an enlarged spleen that may need to be treated with cancer medicine or surgery

The care team will order a comprehensive battery of tests for chronic myeloid leukemia to help ensure that patients and their loved ones receive a detailed, accurate diagnosis.

Chronic Myeloid Leukemia Stages

Unlike many cancers where solid tumors grow and may be measured, CML is a condition that affects the bone marrow. It is categorized by phases rather than stages.

The three CML phases are based primarily on the percentage of immature white blood cells (myeloblasts or blasts) found in the bone marrow. Other factors may also help pinpoint a CML phase, such as the presence of certain symptoms, such as weight loss and fatigue.

CML Chronic Phase

In chronic phase CML, a person has less than 10% myeloblasts in samples of blood and bone marrow. Most people with CML are diagnosed in this phase.

A CML treatment plan may include options such as targeted drug therapy, which tends to be more appropriate for people in this phase of the disease than for those with more advanced CML. These drugs target the abnormal gene that causes CML cells to grow.

CML Accelerated Phase

People in the accelerated phase of CML usually have both blood and bone marrow samples containing 10% to 19% myeloblasts, although these numbers may vary.

Additional factors that may also contribute to an accelerated phase CML diagnosis include those listed below.

Blood samples containing between 15% and 30% myeloblasts: If a blood sample alone shows this level of myeloblasts, it indicates the accelerated phase.

Blood samples containing 20% or more basophils: Basophils are a type of cell that myeloblasts form when they mature.

Blood samples containing 30% or more of both myeloblasts and promyelocytes: Promyelocytes are more mature than myeloblasts, but they haven’t yet completely matured into cells like basophils.

New leukemia cell chromosomal changes: New leukemia cells that have the Philadelphia chromosome may have mutations or additional DNA damage that lead to cellular changes.

Noticeable or increasingly intense symptoms: These may include a decreased appetite, weight loss and fever.

Extremely low blood platelet levels: Counts at or below 100 x 1,000/mm3 that weren’t due to treatment would qualify.

A patient’s care team may recommend additional treatments for patients in the accelerated phase of CML, such as a donor stem cell transplant, immunotherapy or high-dose chemotherapy.

CML Blast Phase

Blast phase CML may be diagnosed when:

• The blood, bone marrow or both contain 20%t or higher levels of myeloblasts
• White blood cell overproduction is challenging to treat

In this phase, cancer has spread beyond the bone marrow to other tissues and organs. Additional symptoms may also appear, such as an enlarged spleen and changes in leukemia cells that give the appearance of the cancer cells found in other types of leukemia.

Treatments in the blast phase may focus on therapies to help improve the patient’s quality of life, like chemotherapy for pain management.

The care team's goal is to improve outcomes by helping patients and their families thoroughly understand a chronic myeloid leukemia diagnosis and to plan a treatment protocol based on test results, doctor recommendations and patient preferences.