Chronic myeloid leukemia (CML) — sometimes called chronic myelogenous leukemia — is a blood cancer that can be treated with several therapies. Many different CML drugs have been discovered and approved in the past couple of decades. These drugs are often very effective and have caused CML survival rates to drastically improve.
CML is an uncommon, slowly progressing type of leukemia, caused by a chromosome mutation. A type of cancer, CML starts in the blood-forming cells of the bone marrow and invades the blood.
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.
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.
Targeted therapies are drugs that recognize and attack molecules specifically found on cancer cells. Often, these abnormal molecules are the result of gene changes.
Most people with CML have a gene change called the Philadelphia chromosome. It is an abnormality that affects a cell’s chromosomes (long pieces of DNA that contain a cell’s genes). The Philadelphia chromosome occurs when part of a chromosome breaks off and attaches to a different chromosome. It creates an abnormal protein called BCR-ABL, which causes too many abnormal white blood cells to form.
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:
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.
Targeted therapies are very effective at treating CML, so chemotherapy is not used as often. If TKIs don’t work, however, chemotherapy drugs may be used. These drugs may include:
Immunotherapy drugs boost your immune system and help it better fight cancer. These medications are also sometimes known as biologics. One immunotherapy used to treat CML is Intron A (interferon alfa-2b). Interferon is not as effective as TKIs, but it may be an option for people who can’t use TKIs, including pregnant women.
Some people with chronic myeloid leukemia have high levels of white blood cells. Too many of these cells can cause damage to different organs and blood vessels. During leukapheresis, a machine removes some of the excess white blood cells. This treatment may be helpful for people who can’t use other CML treatments.
Blood stem cells are found in the 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.
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 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 is often only an option for younger people and people without any other health conditions.
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.
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. Different clinical trials may enroll people before, during, or after receiving treatment. If you are interested in learning more about participating, talk to your health care team.
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 diagnostic tests to measure how many blasts are in your blood and bone marrow. There are three CML phases:
Most people with CML are diagnosed when they are 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.
The goals of treatment for people with chronic-phase CML may include:
The majority of people with CML have very good outcomes after being treated with imatinib or another TKI. If the first TKI does not 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.
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 are able to 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.
People with blast-phase CML should generally get two different tests that can help determine the best treatment options. The first test is to determine 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:
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 getting those genetic tests can help a person learn which TKIs are likely to be the most effective. The TKIs that most often work to treat blast-phase CML are:
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.
The first treatment that you receive for CML may be called initial therapy or front-line therapy. If the leukemia doesn’t respond to initial therapy, the cancer is said to be resistant or refractory to that drug. In the case of refractory leukemia, a different treatment — referred to as 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. However, in some cases, the leukemia can relapse (come back). In this case, additional diagnostic testing may be needed to determine the best treatment options.
Initial treatment with imatinib is usually effective at treating CML. About 80 percent to 90 percent of 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 they may suggest switching to a different TKI drug. Bosutinib and ponatinib are commonly used in CML cases that become resistant to other TKIs.
Chemotherapy may also be used if TKIs aren’t working. In particular, people with chronic- or accelerated-phase CML that is TKI-resistant may be able to try the chemotherapy drug omacetaxine. Clinical trials may also provide ways to access new treatments.
People who undergo 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.
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