chronic myeloid leukemia

What Is Chronic Myeloid Leukemia?

Chronic myeloid leukaemia (CML) is a type of cancer that affects the blood and bone marrow. In CML the bone marrow produces too many white cells, called granulocytes. These cells (sometimes called blasts or leukaemic blasts) gradually crowd the bone marrow, interfering with normal blood cell production. They also spill out of the bone marrow and circulate around the body in the bloodstream. Because they are not fully mature, they are unable to work properly to fight infections. Over time, a shortage of red cells and platelets can cause anaemia, bleeding and/or bruising.

CML usually develops gradually during the early stages of disease, and progresses slowly over weeks or months. It has three phases:

  1. Chronic phase
  2. Accelerated phase
  3. Blast phase.


Chronic phase

Most people (more than 90%) are diagnosed in the early chronic phase of CML. Blood counts remain relatively stable and the proportion of blast cells in the bone marrow and blood is low (five per cent or less). Most people are generally well at this stage and have few, if any, troubling symptoms of their disease. For most people these days, the duration of this phase is substantially longer than five years, and may exceed 10-15 years.

Accelerated phase

After some time and despite treatment, CML begins to change from a relatively stable disease into a more rapidly progressing one. This is known as the accelerated phase of CML. During this time a proportion of blast cells may start to increase in your bone marrow and circulating blood.

Blast phase

Eventually, CML transforms into a rapidly progressing disease resembling acute leukaemia. This is known as the blast phase or blast crisis. It is characterised by a dramatic increase in the number of blast cells in the bone marrow and blood (usually 30% or more) and by the development of more severe symptoms of your disease.  In about two-thirds of cases, CML transforms into a disease resembling acute myeloid leukaemia (AML). The remainder transforms into a disease resembling acute lymphoblastic leukaemia (ALL). Occasionally, the blast cells are said to be undifferentiated or mixed.

Signs and Symptoms of Chronic Myeloid Leukemia

The symptoms of chronic myeloid leukemia (CML) are often vague and are more often caused by other things. They include:

  1. Weakness
  2. Fatigue
  3. Night sweats
  4. Weight loss
  5. Fever
  6. Bone pain (caused by leukemia cells spreading from the marrow cavity to the surface of the bone or into the joint)
  7. An enlarged spleen (felt as a mass under the left side of the ribcage)
  8. Pain or a sense of “fullness" in the belly
  9. Feeling full after eating even a small amount of food


But these aren't just symptoms of CML. They can happen with other cancers, as well as with many conditions that aren't cancer.

Problems caused by a shortage of blood cells

Many of the signs and symptoms of CML occur because the leukemia cells replace the bone marrow's normal blood-making cells. As a result, people with CML don't make enough red blood cells, properly functioning white blood cells, and platelets.

Anemia is a shortage of red blood cells: It can cause weakness, tiredness, and shortness of breath.

Leukopenia is a shortage of normal white blood cells: This shortage increases the risk of infections. Although patients with leukemia may have very high white blood cell counts, the leukemia cells don't protect against infection the way normal white blood cells do.

Neutropenia means that the level of normal neutrophils is low: Neutrophils, a type of white blood cell, are very important in fighting infection from bacteria. People who are neutropenic have a high risk of getting very serious bacterial infections.

Thrombocytopenia is a shortage of blood platelets: It can lead to easy bruising or bleeding, with frequent or severe nosebleeds and bleeding gums. Some patients with CML actually have too many platelets (thrombocytosis). But those platelets often don't work the way they should, so these people often have problems with bleeding and bruising as well.

The most common sign of CML is an abnormal white blood cell count.

What Causes Chronic Myeloid Leukemia?

Chronic myeloid leukemia occurs when something goes awry in the genes of your blood cells. It's not clear what initially sets off this process, but doctors have discovered how it progresses into chronic myeloid leukemia.

First, an abnormal chromosome develops

Human cells normally contain 23 pairs of chromosomes. These chromosomes hold the DNA that contains the instructions (genes) that control the cells in your body. In people with chronic myeloid leukemia, the chromosomes in the blood cells swap sections with each other. A section of chromosome 9 switches places with a section of chromosome 22, creating an extra-short chromosome 22 and an extra-long chromosome 9.

The extra-short chromosome 22 is called the Philadelphia chromosome, named for the city where it was discovered. The Philadelphia chromosome is present in the blood cells of 90 percent of people with chronic myeloid leukemia.

Second, the abnormal chromosome creates a new gene

The Philadelphia chromosome creates a new gene. Genes from chromosome 9 combine with genes from chromosome 22 to create a new gene called BCR-ABL. The BCR-ABL gene contains instructions that tell the abnormal blood cell to produce too much of a protein called tyrosine kinase. Tyrosine kinase promotes cancer by allowing certain blood cells to grow out of control.

Third, the new gene allows too many diseased blood cells

Your blood cells originate in the bone marrow, a spongy material inside your bones. When your bone marrow functions normally, it produces immature cells (blood stem cells) in a controlled way. These cells then mature and specialize into the various types of blood cells that circulate in your body — red cells, white cells and platelets.

In chronic myeloid leukemia, this process doesn't work properly. The tyrosine kinase caused by the BCR-ABL gene causes too many white blood cells. Most or all of these cells contain the abnormal Philadelphia chromosome. The diseased white blood cells don't grow and die like normal cells. The diseased white blood cells build up in huge numbers, crowding out healthy blood cells and damaging the bone marrow.

Risk Factors for Chronic Myeloid Leukemia

A risk factor is something that affects a person's chance of getting a disease such as cancer. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for a number of cancers. But having a risk factor, or even many risk factors, does not mean that you will get the disease. And many people who get the disease may not have had any known risk factors.

The only risk factors for chronic myeloid leukemia (CML) are:

Radiation exposure: Being exposed to high-dose radiation (such as being a survivor of an atomic bomb blast or nuclear reactor accident) increases the risk of getting CML.

Age: The risk of getting CML goes up with age.

Gender: This disease is slightly more common in males than females, but it's not known why.

There are no other proven risk factors for CML. The risk of getting CML does not seem to be affected by smoking, diet, exposure to chemicals, or infections. And CML does not run in families.

Complications of Chronic Myeloid Leukemia

Chronic Myeloid leukemia (CML) can cause a variety of complications, including:

Fatigue: If diseased white blood cells crowd out healthy red blood cells, anemia may result. Anemia can make you feel tired and worn down. Treatment for CML also can cause a drop in red blood cells.

Excess bleeding: Blood cells called platelets help control bleeding by plugging small leaks in blood vessels and helping your blood to clot. A shortage of blood platelets (thrombocytopenia) can result in easy bleeding and bruising, including frequent or severe nosebleeds, bleeding from the gums, or tiny red dots caused by bleeding into the skin (petechiae).

Pain: CML can cause bone pain or joint pain as the bone marrow expands when excess white blood cells build up.

Enlarged spleen: Some of the extra blood cells produced when you have CML are stored in the spleen. This can cause the spleen to become swollen or enlarged. The swollen spleen takes up space in your abdomen and makes you feel full even after small meals or causes pain on the left side of your body below your ribs.

Infection: White blood cells help the body fight off infection. Although people with CML have too many white blood cells, these cells are often diseased and don't function properly. As a result, they aren't able to fight infection as well as healthy white cells can. In addition, treatment can cause your white cell count to drop too low (neutropenia), also making you vulnerable to infection.

Death: If CML can't be successfully treated, it ultimately is fatal.

Diagnosis of Chronic Myeloid Leukemia

Tests and procedures used to diagnose chronic Myeloid leukemia include:

Physical exam: Your doctor will examine you and check such vital signs as pulse and blood pressure. He or she will also feel your lymph nodes, spleen and abdomen for abnormalities.

Blood tests: A complete blood count may reveal abnormalities in your blood cells. Blood chemistry tests to measure organ function may also reveal abnormalities that can help your doctor make a diagnosis.

Bone marrow tests: Bone marrow biopsy and bone marrow aspiration are used to collect bone marrow samples for laboratory testing. These tests involve collecting bone marrow from your hipbone.

Tests to look for the Philadelphia chromosome: Specialized tests, such as fluorescence in situ hybridization (FISH) analysis and the polymerase chain reaction (PCR) test, analyze blood or bone marrow samples for the presence of the Philadelphia chromosome or the BCR-ABL gene.

Phases of chronic Myeloid leukemia

The phase of chronic Myeloid leukemia refers to the aggressiveness of the disease. Your doctor determines the phase by measuring the proportion of diseased cells to healthy cells in your blood or bone marrow. A higher proportion of diseased cells means chronic Myeloid leukemia is at a more advanced stage.

Phases of chronic Myeloid leukemia include:

Chronic: The chronic phase is the earliest phase and generally has the best response to treatment.

Accelerated: The accelerated phase is a transitional phase when the disease becomes more aggressive.

Blastic: Blastic phase is a severe, aggressive phase that becomes life-threatening.

Treatment for chronic Myeloid leukemia

The goal of chronic Myeloid leukemia treatment is to eliminate the blood cells that contain the abnormal BCR-ABL gene that causes the overabundance of diseased blood cells. For most people, it's not possible to eliminate all diseased cells, but treatment can help achieve a long-term remission of the disease.

Targeted drugs

Targeted drugs are designed to attack cancer by focusing on a specific aspect of cancer cells that allows them to grow and multiply. In chronic Myeloid leukemia, the target of these drugs is the protein produced by the BCR-ABL gene — tyrosine kinase. Targeted drugs that block the action of tyrosine kinase include:

  1. Imatinib (Gleevec)
  2. Dasatinib (Sprycel)
  3. Nilotinib (Tasigna)
  4. Bosutinib (Bosulif)
  5. Ponatinib (Iclusig)


Targeted drugs are the initial treatment for most people diagnosed with chronic Myeloid leukemia. If the disease doesn't respond or becomes resistant to the first targeted drug, doctors may consider other targeted drugs, such as omacetaxine (Synribo), or other treatments. Side effects of these targeted drugs include swelling or puffiness of the skin, nausea, muscle cramps, rash, fatigue, diarrhea, and skin rashes.

Doctors haven't determined a safe point at which people with chronic Myeloid leukemia can stop taking targeted drugs. For this reason, most people continue to take targeted drugs even when blood tests reveal a remission of chronic Myeloid leukemia.

Blood stem cell transplant

A blood stem cell transplant, also called a bone marrow transplant, offers the only chance for a definitive cure for chronic Myeloid leukemia. However, it's usually reserved for people who haven't been helped by other treatments because blood stem cell transplants have risks and carry a high rate of serious complications.

During a blood stem cell transplant, high doses of chemotherapy drugs are used to kill the blood-forming cells in your bone marrow. Then blood stem cells from a donor or your own cells that were previously collected and stored are infused into your bloodstream. The new cells form new, healthy blood cells to replace the diseased cells.


Chemotherapy drugs are typically combined with other treatments for chronic Myeloid leukemia. Often, chemotherapy treatment for chronic Myeloid leukemia is given as a tablet you take by mouth. Side effects of chemotherapy drugs depend on what drugs you take.

Biological therapy

Biological therapies harness your body's immune system to help fight cancer. The biological drug interferon is a synthetic version of an immune system cell. Interferon may help reduce the growth of leukemia cells. Interferon may be an option if other treatments don't work or if you can't take other drugs, such as during pregnancy. Side effects of interferon include fatigue, fever, flu-like symptoms and weight loss.

Team Of Consultants

Dr. Dharma Choudhary

Dr.Dharma Choudhary

Director (BMT) - Sanar International Hospital, Gurgram

Dr.Dharma Choudhary

Director (BMT) - Sanar International Hospital, Gurgram
Dr Rahul Bharqava

Dr. Rahul Bhargava

Director & head - Fortis Hospital, Gurgaon

Dr. Rahul Bhargava

Director & head - Fortis Hospital, Gurgaon
Dr. Sunil Kumar Gupta

Dr. Sunil Kumar Gupta

Director & HOD - Venkateshwar Hospital, Delhi

Dr. Sunil Kumar Gupta

Director & HOD - Venkateshwar Hospital, Delhi