CML

CML

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Leukemia

Co-Editors-in-Chief

Charles M. Balch, MD, FACSProfessor of Surgery, The University of Texas MD Anderson Cancer CenterEditor-in-Chief, 
Patient Resource LLCFormer Executive Vice President & CEO, American Society of Clinical OncologyPast President, Society ofSurgical OncologyMichael A. Caligiuri, MDPresident andPhysician-in-Chief, City of Hope National Medical CenterPast President, American Association for Cancer ResearchDavid S. Snyder, MDEmeritus Professor, 
Department of
Hematology/HCT
City of Hope NationalMedical Center

Chronic Myeloid Leukemia

CML is a slow-growing cancer of the bone marrow and blood that begins when a genetic change mutates or damages early (immature) myeloid cells, which are the cells that become white blood cells (other than lymphocytes), red blood cells or cells that make platelets. Most people who have CML have an abnormal chromosome called the Philadelphia chromosome. It results from an abnormal fusion of two genes, BCR and ABL, which then produces the BCR-ABL protein. It is important to test for the Philadelphia chromosome or the BCR-ABL gene fusion, as some treatments are likely to be more effective.

Other chromosomes may begin to mutate in the accelerated and blast phases. Almost all people with CML will have the BCR-ABL gene detected in their blood or bone marrow.

Classifying CML

Your doctor will use a variety of tests to look for leukemic cells, chromosome abnormalities (which may indicate the Philadelphia chromosome), molecular markers and an enlarged spleen. Those tests may include a complete blood count (CBC) with differential, blood chemistry study, a hepatitis panel (to look for hepatitis B, which can occur with CML), bone marrow aspiration and biopsy, molecular tests, cytogenetic analysis, including karyotyping and fluorescence in situ hybridization (FISH), and imaging tests, including computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound.

The World Health Organization (WHO) classification system is used to classify CML into chronic phase, accelerated phase and blast crisis phase (see Table 2). This helps doctors determine the best treatment and prognosis (predicted outcome after treatment). The phases primarily describe the differences in the number of immature white blood cells (myeloblasts or blasts). Other blood cell count levels and chromosome changes are also considered.

The progression of CML in the chronic phase is generally slow, and it may be several months or years before the next phase is reached. Response to treatment is typically better when the treatment begins in this phase. The most advanced and aggressive phase is the blast crisis phase.

It is normal for bone marrow to contain 5 percent blasts. In a person diagnosed with CML, they blasts are usually higher than 5 percent and indicates a more advanced CML.

Treating CML

The following options may be used alone or in combination.

Targeted therapy is the main treatment for chronic phase CML. Targeted therapy that is taken orally (in pill form) is almost always the first line of treatment (meaning the first treatment given) for chronic phase CML. The more advanced stages of CML will usually respond temporarily but quickly require additional treatment; however, when caught in the chronic phase, some patients can receive targeted therapy and remain in remission for many years.

The BCR-ABL gene is a tyrosine kinase protein that helps CML cells grow, and it can be blocked by a tyrosine kinase inhibitor (TKI). Resistance to this type of targeted therapy can develop in patients; when that happens, several other TKIs are available that may work where others have failed. The response to the TKI therapy (complete response, partial response or no response) can be monitored by a blood test.

For some patients who remain in remission long enough, your doctor may consider a trial period off of the TKI targeted therapy. This requires very close blood monitoring to look for signs of relapse of the leukemia, but it can allow some patients to stop taking chemotherapy permanently. 

Chemotherapy may be used for CML that does not respond to targeted therapy or has not improved after treatment with TKIs.

Stem cell transplantation may be an option, especially when disease is in the accelerated or blast phase (see Stem Cell Transplantation, page 8). Allogeneic stem cell recipients may also receive a donor lymphocyte infusion from the original allogeneic blood stem cell donor to boost the attack on leukemia cells. A donor lymphocyte infusion is used to kill the remaining CML cells that have not gone away completely or have come back following the stem cell transplant.

Immunotherapy is not typically used as the first treatment for this disease. Cytokine immunotherapy works by introducing large amounts of the laboratory-made cytokines to the immune system to promote specific immune responses.

As of 10/13/21 

Relapses or Resistant CML

The goal of CML treatment is to reach remission, which occurs when leukemia is not detected in the body and there are no symptoms. However, remission may be temporary or permanent. When CML returns, it is called relapses CML. Sometimes, the leukemia does not respond to treatment or stops responding. This is called resistant CML.