Leukemias

Chronic myeloid leukemia

Diagnosing and treatment of CML

Chronic myeloid leukemia (CML) is a slow-growing leukemia that starts in early myeloid cells, which are the cells that become white blood cells (other than lymphocytes), red blood cells or cells that make platelets.

Human cells contain 23 pairs of chromosomes (long molecules of DNA). Most cases of CML start when two chromosomes “swap” DNA, creating an abnormally short chromosome. The resulting abnormal chromosome, the Philadelphia chromosome, is in the leukemia cells of almost all people with CML. The DNA swap causes the formation of the BCR-ABL gene, which produces the BCR-ABL protein. This protein helps CML to grow. Many CML treatments are designed to block the BCR-ABL protein so it cannot help CML grow.

Diagnosing CML

CML grows slowly, so many people with CML do not have any symptoms when their cancer is diagnosed. The disease is often suspected because of the results of blood tests ordered for another problem or because of findings on a routine physical examination. In addition to a physical exam, blood, bone marrow and genetic testing may be used to diagnose CML. These tests include the following:

  • Complete blood count (CBC) measures the number of white blood cells, red blood cells and platelets in the blood.
  • Bone marrow aspiration and biopsy are often done at the same time. During these procedures, bone marrow tissue samples are removed for examination. A bone marrow biopsy involves removal of a sample of marrow from within the bone (usually the pelvic bone). For bone marrow aspiration, liquid bone marrow is removed, usually from the back of the pelvic bone or the breastbone.
  • Cytogenetic test/karyotype involves examination of chromosomes with a microscope to determine whether the Philadelphia chromosome is present.
  • Fluorescent in situ hybridization (FISH) is done to look for pieces of the BCR-ABL gene on chromosomes.
  • Polymerase chain reaction (PCR) can be used to look for the BCR-ABL gene.

Imaging tests, such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasound and X-ray are not necessary to diagnose CML but may be done to help determine the extent of the disease.

Phases of CML

Most cancers are given a numbered stage based on the size of the tumor and how far the cancer has spread. Staging is different with CML. Instead of numbered stages, CML is classified into three phases that help determine the prognosis (prediction of the outlook): chronic phase, accelerated phase and blast phase (see Table 1). In most cases, CML is in the chronic phase at the time of diagnosis. In this phase, symptoms are typically mild or nonexistent. In the accelerated phase, symptoms may include fever and weight loss. The most advanced and aggressive phase of this disease is the blast phase.

Table 1. Phases of CML

Phase Description
Chronic
▪ Immature (blast) cells make up less than 10% of the cells in bone
Accelerated phase
▪ Blasts make up 10% to 19% of cells in the bone marrow or blood OR
▪ Basophils make up at least 20% of white blood cells OR
▪ High white blood cell counts do not decrease with treatment OR
▪ High or low platelet counts are not caused by treatment OR
▪ New chromosome changes are present in leukemia cells
Blast phase ▪ Blasts make up more than 20% of the cells in bone marrow or blood

Treating CML

After CML is diagnosed and assigned a phase, your health care team will work with you to choose the best treatment option. Targeted therapy is the most common treatment for CML. Immunotherapy, chemotherapy and stem cell transplantation may also be used to treat CML. Participating in a clinical trial is something that should definitely be considered by you and your physician. Surgery and radiation therapy may be used to treat symptoms of CML but are not used to treat CML itself.

  • Targeted therapy is the main treatment for CML. Targeted therapy fights CML by blocking the BCR-ABL protein that help CML cells grow. BCR-ABL is a type of protein called a tyrosine kinase, and drugs that block tyrosine kinases are called tyrosine kinase inhibitors (TKIs). TKIs are the standard treatment for CML and include bosutinib (Bosulif), dasatinib (Sprycel), imatinib (Gleevec), nilotinib (Tasigna) and ponatinib (Iclusig).
  • Immunotherapy stimulates the body’s own immune system to fight cancer. Interferon alfa is an immunotherapy drug that can be used to treat CML, but it is used less often than targeted therapy drugs. It stops the leukemia cells from growing and is given as a daily injection over several years.
  • Chemotherapy drugs, also called cytotoxic drugs, are used to stop the growth of cancer, either by killing cancer cells or by preventing them from dividing and growing. Chemotherapy is considered a systemic treatment because the drugs travel throughout the body in the bloodstream. Chemotherapy may be used if TKIs have stopped working or as part of treatment during stem cell transplantation. Busulfan (Busulfex), cyclophosphamide (Cytoxan), cytarabine, hydroxyurea (Hydrea) and omacetaxine (Synribo) are chemotherapy drugs used for people with CML.
  • Stem cell transplantation (also known as a bone marrow transplant) is an infusion of healthy stem cells into the body. After a person receives high-dose chemotherapy to kill the cancer cells, a transplant can occur. The healthy cells can be collected from blood or bone marrow from the patient. It can also be collected from umbilical cord blood, a family member or another donor. An autologous stem cell transplant is a transplant of the patient’s own stem cells, from either the bone marrow or blood. In an allogeneic stem cell transplant, the stem cells come from a volunteer donor whose tissue type closely matches that of the patient. If available, a sister or brother offers the best chance of a close match. If a sibling or another family member is not a good match, an unrelated volunteer donor may be found through a national registry.

Using the patient’s own stem cells could reintroduce leukemia cells, so allogeneic stem cell transplants are the preferred type of stem cell transplants for people with CML. Stem cell transplantation may be used in younger patients or if targeted therapy is not working well.

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