Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia, is a type of blood cancer that can be treated with different medications. Over the past few decades, researchers have developed several new CML drugs, many of which work very well. Thanks to these treatments, survival rates for CML have improved dramatically.

CML is an uncommon, slowly progressing type of leukemia caused by a chromosome mutation. A mutation is a change in a cell’s DNA, which acts like an instruction manual for the body. In CML, two chromosomes swap pieces, creating an abnormal gene. This gene tells the body to make too many white blood cells, leading to leukemia. CML starts in the blood-forming cells of the bone marrow and spreads into the blood.

Treatments for CML

When recommending leukemia treatments, your doctor will take into account several different factors, such as:

• Your age
• Your overall health
• How many blast cells (immature white blood cells) are in your blood or bone marrow
• Your blood cell count
• How big your spleen is

These factors provide a clue as to how severe your leukemia is and what types of treatments you can safely tolerate. This information helps you and your doctor understand whether more aggressive or less aggressive treatments may be a better fit for you.

Targeted therapies are very effective at treating CML, so chemotherapy is not used as often.

Additionally, CML is treated differently depending on the phase of the condition. The phase describes how quickly your leukemia is growing and how advanced it is. Your phase will determine which treatment options are available to you.

1. Targeted Therapy

Targeted therapies recognize and attack molecules specifically found on cancer cells. These abnormal molecules are often the result of gene changes.

Most people with CML have a genetic change called the Philadelphia chromosome. This abnormality affects a cell’s chromosomes — long strands of DNA that hold genetic instructions. It happens when a piece of one chromosome breaks off and attaches to another, creating an abnormal protein called BCR-ABL. This protein tells the body to make too many abnormal white blood cells. The Philadelphia chromosome was named after the city where scientists discovered it in 1960.

BCR-ABL is in the tyrosine kinase family of proteins and can be blocked with drugs called tyrosine kinase inhibitors (TKIs). Some TKIs used to treat CML include:

• Asciminib (Scemblix)
• Bosutinib (Bosulif)
• Dasatinib (Sprycel)
• Imatinib (Gleevec)
• Nilotinib (Tasigna/Danziten)
• Ponatinib (Iclusig)

Most people need to take TKIs long term to prevent CML from returning. Eventually, if the medication seems to be working well, some people may be able to take a lower dose or stop using the drug altogether.

2. Chemotherapy

Targeted therapies are very effective at treating CML, so chemotherapy is not used as often. However, chemotherapy can be used in certain cases, such as CML in the blast phase. These drugs may include:

• Ara-C (Cytarabine)
• Busulfex (Busulfan)
• Cyclophosphamide (Cytoxan)
• Hydrea (Hydroxyurea)
• Vincristine sulfate (Marqibo)

3. Immunotherapy

Immunotherapy drugs boost your immune system and help it better fight cancer. These medications are sometimes called biologics, meaning they are made from living cells.

One immunotherapy sometimes used to treat CML is interferon alfa-2b (Intron A). Interferon is not as effective as TKIs, but it may be an option for people who can’t use TKIs, including those who are pregnant.

4. Leukapheresis

Some people with CML have high levels of white blood cells. Too many of these cells can cause damage to different organs and blood vessels. Leukapheresis is a treatment in which excess white blood cells are removed via a filtering machine. This procedure may be helpful for people who can’t use other CML treatments.

5. Stem Cell Transplant

Blood stem cells are found in bone marrow (spongy tissue inside of certain bones). They make all of the other types of cells found in the blood. Some people with CML get an allogeneic stem cell transplant, in which they receive new stem cells from a donor.

Stem cell transplantation is the treatment most likely to cure CML but it's risky and can cause serious side effects.

Before undergoing a stem cell transplant (also sometimes called a bone marrow transplant), a person will receive high doses of chemotherapy. This high-dose treatment kills off leukemia cells — but also generally damages healthy blood cells. A delivery of healthy stem cells after treatment allows the body to replace the old blood cells.

Stem cell transplantation is the treatment that is most likely to cure CML. However, this procedure is risky and can cause serious side effects. It’s often only an option for younger people and those without any other health conditions.

Donor Lymphocyte Infusion

Some people have a donor lymphocyte infusion (DLI) after having a stem cell transplant. During a DLI, lymphocytes (white blood cells) are taken from the same donor who provided stem cells for the transplant. When the new lymphocytes are delivered to the person with CML, the lymphocytes attack the leukemia cells.

6. Surgery

CML may lead to an enlarged spleen in some people. If other therapies don’t help treat this symptom, the spleen may need to be removed in a procedure called a splenectomy.

7. Radiation Therapy

People with CML rarely undergo radiation therapy. This treatment uses high-energy beams to kill leukemia cells. Radiation therapy may be used to reduce symptoms, such as an enlarged spleen or bone pain.

8. Clinical Trial

Clinical trials aim to improve treatment options for everyone living with CML. These trials help researchers understand whether certain treatments are safe and effective. Clinical trials can also help people with CML access treatments that wouldn’t otherwise be available. However, clinical trials may also come with risks, such as unknown side effects or treatments that may not work as expected. Different clinical trials may enroll people before, during, or after receiving treatment. If you’re interested in learning more about participating, talk to your healthcare team.

Treatment by Phase of Chronic Myeloid Leukemia

Many cancers are classified by stages that describe how far the cancer has spread. Instead of stages, CML is divided into phases. To determine the CML phase, your doctor will use tests to measure how many blasts are in your blood and bone marrow. There are three CML phases:

• The chronic phase is the earliest and least aggressive stage. Fewer than 10 percent of blood cells are blasts (immature cells), and symptoms may be mild or even unnoticed.
• In the accelerated phase, the leukemia is getting worse. Between 10 percent and 19 percent of blood cells are blasts, and symptoms like fatigue, fever, or weight loss may appear.
• The blast phase is the most severe stage. At least 20 percent of blood cells are blasts, making it harder for the body to fight infections and control bleeding. This phase acts more like acute leukemia and needs urgent treatment.

Most people with CML are diagnosed when they’re in the chronic phase. There are certain treatments that are usually used when a person is in this phase. Later, if CML progresses to a different stage, doctors may recommend other treatments.

Chronic-Phase Treatments

The goals of treatment for people with chronic-phase CML may include:

• Relieving symptoms
• Eliminating leukemia cells
• Preventing CML from moving to the blast phase

The majority of people with CML have very good outcomes after being treated with imatinib or another TKI. If the first TKI doesn’t seem to be working, a doctor may recommend changing doses or trying a different TKI. Occasionally, people with chronic-phase CML may be able to get a stem cell transplant.

Accelerated-Phase Treatments

The treatment goal for accelerated-phase CML is usually to kill cancer cells and help a person go into remission, in which leukemia signs and symptoms go away. In some cases, the goal may be to help the leukemia go back to the chronic phase.

TKIs may not be as effective for people in the accelerated phase. They may help people go into remission, but the CML often comes back within about two years. Stem cell transplants may be a good option for people in the accelerated phase who can tolerate the side effects.

Cells in accelerated-phase CML often have additional gene changes compared to the leukemia cells found in chronic-phase CML. Genetic testing can help people in the accelerated phase learn more about which treatments may be most effective.

Blast-Phase Treatments

Generally, people with blast-phase CML should get two specific tests that can help determine their best treatment options. The first test shows whether the CML cells are myeloid or lymphoid (two different forms of white blood cells). The second looks for mutations in BCR-ABL.

If a person’s leukemia cells are myeloid, they may be able to use chemotherapy treatments that are normally used to treat acute myeloid leukemia (AML). However, remission only occurs in about 20 percent of people with blast-phase myeloid cells.

On the other hand, some people with blast-phase CML have lymphoid cells that are similar to the cells seen in acute lymphoblastic leukemia (ALL). Chemotherapy often works better in these cases. Chemotherapy drugs may include:

• Doxorubicin (Adriamycin)
• Imatinib
• Prednisone
• Vincristine

People with lymphoid cells may need to get chemotherapy injected into the spinal cord or brain to treat leukemia cells that can spread there.

TKI drugs don’t work as well for people with blast-phase CML. TKIs often only help control CML for a few months. Some BCR-ABL mutations make leukemia cells more resistant or more sensitive to TKIs, so having genetic testing can help determine which TKIs are likely to be the most effective. The TKIs that most often work to treat blast-phase CML are:

• Bosutinib
• Dasatinib
• Nilotinib

People with blast-phase CML may be able to try a stem cell transplant, use chemotherapy drugs in addition to TKIs, or join clinical trials.

Treating Resistant or Relapsed CML

The first treatment that you receive for CML may be called initial therapy or first-line therapy. If the leukemia doesn’t respond to initial therapy, the cancer is said to be resistant or refractory. In the case of refractory leukemia, a different treatment — or second-line therapy — is tried. If second-line therapy is also ineffective, third-line therapy may be an option.

Many people with CML go into remission permanently. Sometimes, however, the leukemia can relapse (come back). In this case, additional testing may be needed to determine the best treatment options.

Treatments for Resistant or Refractory CML

Initial treatment with imatinib is usually effective at treating CML. Most people who use this drug have no remaining signs of cancer cells. However, sometimes the drug stops working over time. In such cases, doctors may recommend increasing the imatinib dose or switching to a different TKI drug. Bosutinib and ponatinib are commonly used in CML cases that become resistant to other TKIs. Asciminib is another TKI option for refractory CML.

Chemotherapy may be used if TKIs don’t work, especially for those with chronic- or accelerated-phase CML that doesn’t respond to TKIs. Clinical trials can also help people try new treatments.

Treatments for Relapsed CML

People who experience a CML relapse often use the same types of treatments as they did the first time, or they may try new therapies. Sometimes, previous drugs are given at new doses or used in different combinations.

Ask Your Doctor

If you have CML, your doctor can help you find the best treatment plan. They can explain your options, check how well your treatment is working, and make changes if needed. If you have questions about side effects, drug resistance, or new treatments, don’t be afraid to ask. Learning more about your care can help you manage CML and feel more in control of your health.

Talk With Others Who Understand

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