Chronic Myeloid Leukemia

Darah

Table of Contents

Chronic myeloid leukemia is a type of white blood cell cancer. White blood cells serve to help your body fight infection. Your blood cells are formed in the bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. These cells expel healthy blood cells, making it difficult for the blood to do its job. In chronic myeloid leukemia (CML), there are too many granulocytes – which is a type of white blood cell.

In general, chronic myeloid leukemia does not cause any symptoms. If you have symptoms, they may include:

  • Fatigue
  • Weight loss
  • Night sweats
  • Fever
  • Pain or a feeling of fullness below the ribs on the left side

To diagnose chronic myeloid leukemia, a blood and bone marrow test is performed. Treatment includes chemotherapy, stem cell transplant, infusion of the donor’s white blood cells after stem cell transplant, surgical removal of the spleen, and biological and targeted therapy. Biological therapy increases your body’s own ability to fight cancer. Targeted therapy uses substances that attack cancer cells without damaging normal cells.

Overview of Chronic Myeloid Leukemia

Chronic myelogenous leukemia is a disease in which the bone marrow produces too many white blood cells.

Chronic myelogenous leukemia (also called CML or chronic granulocytic leukemia) is a slow-progressing blood and bone marrow disease that usually occurs during or after middle age, and rarely occurs in children.

Bone consists of compact bone, spongy bone, and bone marrow. Compact bone forms the outer layer of bone. Spongy bones are located at the ends of the bones and contain red bone marrow. Bone marrow is usually found in the centre of most bones and has many blood vessels. There are two types of bone marrow: red and yellow. Red bone marrow contains blood stem cells that can turn into red blood cells, white blood cells, or platelets. Meanwhile, yellow bone marrow is mostly made of fat.

Leukemia can affect red blood cells, white blood cells, and platelets.

Normally, the bone marrow makes blood stem cells (immature cells) that become mature blood cells over time. Blood stem cells can become myeloid stem cells or lymphoid stem cells. Lymphoid stem cells become white blood cells.

Myeloid stem cells form one of three types of mature blood cells:

  • Red blood cells that carry oxygen and other substances to all body tissues.
  • Platelets that form blood clots to stop bleeding.
  • Granulocytes (white blood cells) that fight infection and disease.

Blood stem cells go through several steps to become red blood cells, platelets, or white blood cells.

In chronic myeloid leukemia, too many blood stem cells become a type of white blood cell called granulocytes. This form of abnormal white blood cells are not healthy. Granulocytes are also called leukemia cells. Leukemia cells can build up in the blood and bone marrow so there is less room for healthy white blood cells, red blood cells, and platelets. When this happens, infection, anemia, or bleeding easily occurs.

Signs and Symptoms of Chronic Myeloid Leukemia

The following are signs and symptoms that may be caused by Chronic Myeloid Leukemia. Check with your doctor if you experience any of the following symptoms: 

  • Fatigue
  • Weight loss for no apparent reason.
  • Night sweats.
  • Fever.
  • Pain or a feeling of fullness below the ribs on the left side

In some cases, CML causes no symptoms at all.

Most people with Chronic Myeloid Leukemia have a gene muation called the Philadelphia chromosome.

Every cell contains DNA (genetic material) which determines how cells look and act. DNA is found in chromosomes. In Chronic Myeloid Leukemia, a piece of DNA from one chromosome moves to another. This change is known as “Philadelphia chromosome”, which produces bone marrow that makes an enzyme called tyrosine kinase – causing too many stem cells to become white blood cells (granulocytes or blasts).

The Philadelphia chromosome is not passed from parent to child.

A piece of chromosome 9 and a piece of chromosome 22 break off and switch places. The bcr-abl gene is formed on chromosome 22 where pieces of the chromosome 9 attach. The change in chromosome 22 is called the Philadelphia chromosome.

Diagnosis of Chronic Myeloid Leukemia

The following tests and procedures can be used to diagnose CML:

  • Physical test and medical history: A physical test is done to check for general signs of health, including signs of disease (e.g. enlarged spleen). A medical history reviews the patient’s health habits and previous illnesses and medical treatments
  • Complete blood count (CBC) with differential test: A procedure that takes a blood sample which is tested for for the following purposes:
    • The red blood cells and platelets count
    • The type of white blood cells count
    • The amount of hemoglobin (a protein that carries oxygen) in red blood cells.
    • The portion of the blood sample made up of red blood cells.

The blood sample is taken by inserting a needle into the vein – allowing blood to flow into the tube. The blood sample is sent to the laboratory and red blood cells, white blood cells, and platelets are counted. CBC is performed to test, diagnose and monitor a variety of conditions.

  • Blood chemistry study: A procedure in which a blood sample is examined to measure the amount of certain substances released into the blood by organs and tissues. Unusual amounts of substance (higher or lower than normal) can be a sign of disease.  
  • Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hip or sternum. The bone marrow, blood, and bone are viewed under a microscope to look for abnormal cells.

After a small area of ​​skin is numbed, a bone marrow needle is inserted into the patient’s hip bone. The samples of blood, bone, and bone marrow are removed to be viewed under a microscope.

One of the following tests can be done to examine the samples of blood or bone marrow tissue removed:

  • Cytogenetic analysis: A test in which cells in a blood or bone marrow sample are viewed under a microscope to look for certain changes in chromosomes, such as the Philadelphia chromosome.
  • FISH (fluorescence in situ hybridization): A laboratory test to look at genes or chromosomes in cells and tissues. DNA fragments containing fluorescent dye are made in the laboratory and added to the cells or tissues on glass slides. When these DNA pieces bind to specific genes or chromosome areas on the slide, they light up under a microscope using a special light.
  • Reverse transcription-polymerase chain reaction (RT-PCR): A laboratory test in which cells in a tissue sample are studied using chemicals to look for specific changes in the structure or function of genes.

Prognosis of Chronic Myeloid Leukemia 

Prognosis (chances of recovery) and treatment options for CML depend on the following factors: 

  • Age.
  • Phase of CML
  • The number of blasts in the blood or bone marrow.
  • The size of spleen when diagnosed.
  • The patient’s general health.

Stages of Chronic Myeloid Leukemia

Staging is a process used to determine how far the cancer has spread. To determine the right treatment, it is important to know the stage of the disease. There is no standard staging for chronic myelogenous leukemia (CML). Instead, the disease is classified into phases: chronic phase, accelerated phase, or blast phase. Tests and procedures that are done to find and diagnose chronic myelogenous leukemia also determine the treatment plan.

Chronic Myeloid Leukemia has 3 phases. 

When there is an increased number of blast cells in the blood and bone marrow, this means less room for healthy white blood cells, red blood cells, and platelets. This can lead to infection, anemia, and easy bleeding, as well as bone pain or a feeling of fullness below the ribs on the left side. The number of blast cells and the severity of CML symptoms determine the phase of the disease.

Chronic Phase

In the chronic phase of chronic myelogenous leukemia, less than 10% of the cells in the blood and bone marrow are blast cells.

Accelerated phase

In the accelerated phase of chronic myelogenous leukemia, 10% to 19% of the cells in the blood and bone marrow are blast cells.

Blast phase

In the blast phase of chronic myelogenous leukemia, 20% or more of the cells in the blood or bone marrow are blast cells. If you experience fatigue, fever, and an enlarged spleen during this phase, it is known as a blast crisis.

Relapse in Chronic Myelogenous Leukemia

In relapsed chronic myelogenous leukemia, the number of blast cells increases after remission.

Treatment for Chronic Myelogenous Leukemia

A variety of treatments are available to treat chronic myelogenous leukemia. Some are standard treatments, and some are still in clinical trials. A clinical trial is research intended to help improve current treatments or gather information about new treatments for cancer patients. When clinical trials show that the new treatment is better than standard treatment, the new treatment can become the standard treatment. Certain clinical trials are only open to patients who have not undergone any treatment. 

Six chronic myelogenous leukemia treatments 

Targeted Therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without damaging normal cells. Tyrosine kinase inhibitor is a type of targeted therapy used for the treatment of chronic myelogenous leukemia.

Imatinib, Mesylate, nilotinib, dasatinib, and ponatinib are tyrosine kinase inhibitors used to treat CML.

Chemotherapy

Chemotherapy uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Either through oral or injection chemotherapy, the drugs enter the bloodstream and reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, organs, or body cavities (e.g. the stomach), or when the drugs mainly affect cancer cells in the areas concerned, that is referred to as regional chemotherapy. Chemotherapy will depend on the type and stage of cancer. 

Biological therapy

Biological therapy is a treatment that uses a patient’s immune system to fight cancer. Substances produced by your body or created in the laboratory are used to enhance, direct, or restore the body’s natural defenses against cancer. This cancer treatment is also called biotherapy or immunotherapy.

Stem cell transplantation with high-dose chemotherapy

Stem cell transplantation with high-dose chemotherapy is a method of administering high-dose chemotherapy and replacing blood-forming cells that are destroyed by cancer treatment. Stem cells (immature blood cells) are removed from the donor blood or bone marrow for later to be frozen and stored. After chemotherapy, the stored stem cells are thawed and given back to the patient through an IV. These reinfused stem cells grow into (and restore) the body’s blood cells.

  • Step 1: Blood sample is taken from a vein of the donor’s arm. Blood flows through a machine that removes the stem cells. Then, the blood is returned to the donor through a vein in the other arm.
  • Step 2: The patient receives chemotherapy to kill blood-forming cells. The patient may receive radiation therapy.
  • Step 3: The patient receives stem cells through a catheter inserted into a vein in the chest.

Donor lymphocyte infusion (DLI)

Donor lymphocyte infusion (DLI) is a cancer treatment used after a stem cell transplantation. Lymphocytes (a type of white blood cell) from the donor’s stem cell transplant are removed from the donor’s blood and may later be frozen or stored. Donor lymphocytes are thawed if previously frozen and then given to the patient through one or more intravenous infusions. The lymphocytes see the patient’s cancer cells as not belonging to the body and attack them. 

Surgery

Splenectomy is a surgical removal of the spleen.

Stage-based treatments of Chronic Myelogenous Leukemia 

Chronic phase of Chronic Myelogenous Leukemia

Treatment for chronic phase myelogenous leukemia may include the following:

  • Targeted therapy with tyrosine kinase inhibitors.
  • High-dose chemotherapy with donor stem cell transplant.
  • Chemotherapy.
  • Splenectomy.
  • Blood stem cell transplant with low-dose chemotherapy
  • New clinical trials 

Accelerated Phase of Chronic Myelogenous Leukemia 

Treatment for the accelerated phase of chronic myelogenous leukemia may include the following:

  • Donor stem cell transplant.
  • Targeted therapy with tyrosine kinase inhibitors.
  • Tyrosine kinase inhibitor therapy followed by blood stem cell transplantation.
  • Biological therapy (interferon) with or without chemotherapy.
  • High-dose chemotherapy.
  • Chemotherapy.
  • Transfusion therapy to replace red blood cells, platelets, and sometimes white blood cells, to relieve symptoms and improve quality of life.
  • New clinical trials 

Blast Phase of Chronic Myelogenous Leukemia 

Treatment for the blast phase of chronic myelogenous leukemia may include the following:

  • Targeted therapy with tyrosine kinase inhibitors.
  • Chemotherapy with one or multiple medications.
  • High-dose chemotherapy.
  • Stem cell transplant.
  • Chemotherapy as palliative therapy to relieve symptoms and improve quality of life.
  • New clinical trials 

Relapse in Chronic Myelogenous Leukemia 

Treatment for relapsed chronic myelogenous leukemia may include the following:

  • Targeted therapy with tyrosine kinase inhibitors.
  • Donor stem cell transplant.
  • Chemotherapy.
  • Donor lymphocyte infusion.
  • Biological therapy (interferon).
  • New clinical trials or higher doses of targeted therapy or donor stem cell transplant.

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