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Chronic Myelogenous Leukemia Phases and Treatment

What's Happening in Your Blood?

Chronic myelogenous leukemia (also called chronic myeloid leukemia) is a rare cancer that affects bone marrow. That's where blood cells are made. With CML, the bone marrow makes many abnormal white blood cells that don't fight infection as well as the various types of normal white blood cells. As they build up in the blood and bone marrow, the abnormal cells crowd out healthy white blood cells, red blood cells, and platelets.

The Philadelphia Chromosome

People with CML have an abnormal chromosome called the Philadelphia chromosome. Chromosomes carry genes, which tell cells what to do. In CML, pieces of chromosomes 9 and 22 break and switch places. The changed chromosome 22 is called the Philadelphia chromosome. It carries a new gene called bcr-abl, which calls for a protein (tyrosine kinase) to be made, triggering stem cells to create abnormal white blood cells found in CML.

CML Phases: Chronic Phase

The chronic phase is the first period of CML. Most people in this phase don't have any symptoms. They're usually diagnosed during a routine blood test. Because there are only a small number of abnormal white blood cells in the blood and bone marrow, the body is still able to fight infection. Even though you might not feel sick now, it's important to get treated so CML doesn't progress to the next phase.

CML Accelerated Phase

During this phase, you may develop symptoms such as fatigue, weight loss, shortness of breath, or fever. This means the number of abnormal blood cells has increased. Once in this phase, it may become harder to achieve remission with CML treatments. The accelerated CML phase can lead to the most serious and aggressive phase of the cancer, blast phase.

CML Blast Phase

By this phase, the number of abnormal blood cells in your bone marrow and blood is high. Meanwhile, the amount of healthy red and white blood cells and platelets has dropped. With fewer disease-fighting white blood cells, you're more likely to get infections. You may have anemia or uncontrolled bleeding. This stage is severe and life-threatening.

Targeting the Abnormal CML Protein

The chronic phase of CML is first treated with targeted drugs called tyrosine kinase inhibitors (TKIs). These medicines can control the disease long term in many patients. Fewer people need transplants now. The TKIs kill off CML blood cells by blocking the protein made by the abnormal gene bcr-abl. Side effects can include rashes and swollen skin, nausea, muscle cramps, and diarrhea. When TKIs can't control the disease, there are other treatment options.

Stem Cell Transplant

A stem cell transplant is an option for some people who don't respond to TKIs. First, you get high doses of chemotherapy drugs to kill blood-forming stem cells in your bone marrow. Then, you receive stem cells from a matched donor. These will form new, healthy blood cells. A stem cell transplant is the only way to cure CML. But newer treatments that target bcr-abl can also normalize the Philadelphia chromosome and help many people with CML achieve remission.

Can I Get a Stem Cell Transplant?

The best candidates for a stem cell transplant:

  • Are younger rather than older patients
  • Are in the chronic phase of CML
  • Are in overall good health
  • Have a matched stem cell donor (preferably a close relative, such as a brother or sister)

The high doses of chemotherapy needed for transplants pose risks. Side effects can include infection and anemia. As you recover, most side effects will go away. There is a risk of permanent infertility, though.

Other CML Treatment Options

If TKIs aren't working and you're not a candidate for a stem cell transplant, other treatment options include:

  • Chemotherapy drugs taken by mouth to kill abnormal cells throughout your body, such as hydroxyurea or busulfan
  • Biological therapies, like interferon, that stimulate your immune system to fight off the cancer
  • New, experimental CML treatments you can try if you enroll in a clinical trial

Monitoring CML Treatment

When you have CML, you'll see your doctor at least every few months to monitor treatment and check for side effects. CML tests include:

  • Complete blood count and bone marrow tests to measure red and white blood cells and platelets
  • Fluorescent in situ hybridization (FISH) test to see how many cells contain the Philadelphia chromosome
  • Polymerase chain reaction (PCR) test to look for the bcr-abl gene

Questions About Your Treatment

Here are a few questions to ask your doctor while you're getting treated for CML:

  • What CML phase am I in?
  • What are my treatment options, and what are the possible side effects?
  • Should I get a second opinion?
  • Can I enroll in a clinical trial of an experimental treatment?

Be Active in Your Treatment

During your treatment for CML, here are a few ways to help yourself feel better:

  • Go to all of your check-ups so your doctor can change treatment if it isn't working.
  • Tell your doctor about any side effects you have.
  • If you're struggling with your illness, get support from friends, family members, or your medical team.

Signs Your Treatment Is Working

When you go for regular checkups, your doctor will look for these signs that your treatment is working:

  • Hematologic response: An improvement in the number of healthy white blood cells and platelets
  • Cytogenetic response: Fewer Philadelphia chromosome-positive cells in your blood and bone marrow
  • Molecular response: Fewer cells with the bcr-abl cancer gene

Am I in CML Remission?

You are considered to be in remission when:

  • Your blood cell count is normal (complete hematologic response).
  • No cells with the Philadelphia chromosome can be found in your blood or bone marrow (complete cytogenetic response).
  • None of the abnormal gene can be found in your blood (complete molecular response).

Being in remission isn't the same as being cured. The cancer can return.

Watch for Signs of Relapse

CML can come back even after it's been successfully treated. Signs of relapse include fatigue or weakness, weight loss, fever, night sweats, bone pain, swelling or pain on the left side (a sign of an enlarged spleen), and a feeling of fullness in the belly. If you have any of these symptoms, call your doctor.

Why Isn't My Treatment Working?

CML therapy works well for most people, but not everyone. Reasons why treatment might stop working include the cancer cells change (mutate) or not enough of medication is getting into your bloodstream. If your treatment isn't effective, your doctor may adjust your drug doses or switch you to another therapy.

Coping With Chronic Myelogenous Leukemia

Reviewed by Arefa Cassoobhoy, MD, MPH on January 27, 2014

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