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The five-year survival rate of chronic myeloid leukemia (CML) has more than doubled in recent years with 70 percent of patients surviving for more than 5 years.

Previously, the typical survival rate of chronic myeloid leukemia (CML) was three to five years.

• With advancements in diagnostic and treatment strategies, survival rates increased beyond five years, following CML diagnosis.
• Since then, the five-year survival rate has more than doubled in recent years. 
• This has been made possible by advancements in medications; patients who receive adequate targeted therapy after being diagnosed with CML have higher survival rates.

In general, the five-year survival rate is about 70 percent for patients with CML. Younger people have a better prognosis. Survival rates largely depend on the stage of the disease and the patient’s general health.

What is chronic myeloid leukemia?

Chronic myeloid leukemia (CML), also referred to as chronic myelogenous leukemia, is a slow-progressing malignancy that starts in the blood-forming cells of the bone marrow. It is characterized by an overproduction of white blood cells that do not mature and, as a result, are unable to perform their intended job.

CML is distinguishable from other types of leukemia by a genetic mutation in white blood cells in the bone marrow known as the Philadelphia (Ph) chromosome.

• This promotes cancer cell division and appears to be present in approximately 90 percent of CML cases.
• The Ph chromosome is generated when two chromosomes, 9 and 22, exchange some of their gene material in a process called translocation.
• The ABL gene from chromosome 9 is fused with the BCR gene on chromosome 22 forming a BCR-ABL fusion gene.

The cause of this chromosomal anomaly is unclear. However, it is predicted that exposure to very high doses of radiation may increase CML risk.

The risk of CML is higher in men and older individuals.

What are the symptoms of chronic myeloid leukemia?

Although most of the patients with chronic myeloid leukemia (CML) do not present with any symptoms in the early stages, there are a few signs associated with CML, which include:

• Fatigue
• Lethargy (lack of energy)
• Breathing difficulties
• Pain or discomfort below the ribs on the left side
• Dizziness
• Unexplained weight loss
• Fever
• Night sweats

3 phases of chronic myeloid leukemia

Chronic myeloid leukemia (CML) is classified into three stages to assist doctors to plan therapy and estimating prognosis or the possibility of recovery.

1. Chronic phase:
   • The chronic phase is the initial stage of developing cancer, and the cancer cells grow very slowly.
     • The undeveloped, immature white blood cells are known as blasts.
     • During this stage, the total number of blast cells in the blood and bone marrow is less than 10 percent.
     • A patient may remain in this stage for several years. However, if treatment is not effective, the illness may advance to accelerated or blast phases.
   • The diagnosis of CML is generally done after testing blood for other reasons.
     • During such accidental diagnosis, it is noted that approximately 90 percent of patients have chronic phase CML.
     • Some patients with chronic phase CML exhibit symptoms at the time of diagnosis, whereas others do not. However, as treatment begins, the majority of the symptoms disappear.
2. Accelerated phase:
   • There is no universally accepted definition of the accelerated phase. However, during the accelerated phase, the cancer cells multiply and develop at a faster rate.
     • The majority of individuals with this stage of CML have 10 to 19 percent blasts in both the blood and bone marrow or more than 20 percent basophils in peripheral blood. Basophils are a type of white blood cell.
     • Because of extra DNA damage and mutations in CML cells, these cells may have new chromosomal abnormalities in addition to the Philadelphia (Ph) chromosome.
3. Blast phase:
   • During the blast phase, the abnormal cells grow out of control, and there are 20 percent or more blasts in the blood or bone marrow.
     • Controlling white blood cells during this phase is quite challenging.
     • The cancer cells may have other genetic mutations.
   • The blast cells can resemble the immature cells observed in individuals with other types of leukemia such as acute lymphoblastic leukemia and acute myeloid leukemia.
     • Patients in the blast phase frequently experience a fever, an enlarged spleen, weight loss, and an overall feeling of being poorly.
   • Knowing the phase of CML is essential for planning the treatment and estimating the survival rate of the patient.
     • Without successful treatment, CML in the chronic phase will progress to the accelerated phase first and subsequently to the blast phase three to four years following diagnosis.

Patients with more blasts or a higher number of basophils, chromosomal alterations other than the Ph chromosome, a high number of white blood cells, or a very enlarged spleen are more likely to undergo the blast phase sooner.

What is leukemia?
See Answer

How is chronic myeloid leukemia diagnosed?

Most patients with chronic myeloid leukemia (CML) are symptom-free in the early stages and are only diagnosed with CML while having a routine blood checkup or to rule out another disease.

Once the patient is known to have an abnormal white blood cell count or present with symptoms of cancer, they may be subjected to a series of tests to confirm the diagnosis.

• Blood test:
  • Blood is drawn from the patient’s veins and is sent to a lab for a complete blood count.
  • A smear of blood is studied under a microscope, which is when the patient’s numerous immature white blood cells known as myeloblast or blasts are observed.
  • This gives the primary diagnosis of leukemia, and the patient undergoes various other tests to determine the diagnosis.
• Bone marrow aspiration:
  • The patient undergoes bone marrow aspiration; the sample is extracted from the hip bone or breastbone.
  • This is a painful procedure, so it is done under the influence of local anesthesia.
  • After giving anesthesia, a thin needle is inserted into the bone, and some liquid bone marrow (inner tissue) is extracted into the syringe.
• Bone marrow biopsy:
  • Following aspiration of liquid, a small piece of the bone and marrow is removed using a larger needle.
  • Although the patient may be in anesthesia, there may be pain while performing and following the procedure. Samples are then sent for analysis.
• Cytogenetic analysis:
  • The study of chromosomes and chromosomal disorders is known as cytogenetics.
    • Under a microscope, bone marrow samples are evaluated for chromosomal alterations or abnormalities such as the Philadelphia (Ph) chromosome.
    • The presence of the Ph chromosome in bone marrow cells, in addition to a high white blood cell count and other typical blood and bone marrow test findings, confirms the diagnosis of CML.
  • The Ph chromosome is identified using cytogenetic analysis in the bone marrow cells of around 95 percent of people with CML.
    • Although a tiny minority of people with CML do not have a cytogenetically detectable Ph chromosome, they virtually invariably test positive for the BCR-ABL1 fusion gene on chromosome 22 using other tests.
• Fluorescence in situ hybridization (FISH):
  • FISH is a laboratory test that looks at genes and chromosomes in cells and is a more sensitive test to diagnose CML than traditional cytogenetic tests.
    • The presence of the BCR-ABL1 gene may be detected through FISH.
  • FISH locates BCR and ABL1 genes in chromosomes by using color probes that are attached to the DNA. Both BCR and ABL1 genes are tagged with various compounds, each of which produces a distinct color.
    • The color appears on the chromosome that has the gene.
    • ABL1 gene is on chromosome 9, and the BCR gene is on chromosome 22. 
    • FISH detects the fragment of chromosome 9 that has shifted to chromosome 22 in CML cells.
    • Overlapping colors of two probes represent the BCR-ABL1 fusion gene.
• Quantitative polymerase chain reaction (qPCR):
  • The most sensitive test for detecting and quantifying the BCR-ABL1 gene in blood or bone marrow samples is qPCR.
    • It can identify small quantities of the BCR-ABL1 gene to a level of one CML cell in a background of 100,000 to 1,000,000 normal cells.

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What are the treatment options for chronic myeloid leukemia?

Treatment is planned according to the type of phase of the disease, side effects following treatment, and the overall health of the patient.

An oncologist who specializes in cancer may work with a hematologist who specializes in blood disorders along with other specialties to treat chronic myeloid leukemia (CML) and various other types of blood cancer.

Treatment of CML may include:

Targeted therapy

Targeted therapy is a type of cancer treatment in which medications or other substances are used to locate and kill specific cancer cells.

Targeted treatments are less likely to kill normal cells than chemotherapy or radiation therapy.

Drugs used for targeted therapy of CML include:

• Imatinib mesylate
• Dasatinib
• Nilotinib
• Ponatinib
• Bosutinib

These drugs are tyrosine kinase inhibitors that inhibit the enzyme tyrosine kinase, which causes stem cells to multiply into more immature white blood cells (blasts).

Chemotherapy

Chemotherapy is a cancer treatment that uses medications to halt the growth of cancer cells, either by killing them or preventing them from multiplying.

• Chemotherapy medications are given orally or injected into a vein or muscle.
• On entering the blood circulation, drugs reach cancer cells throughout the body.

A chemotherapy regimen consists of a particular number of cycles to be given at a certain time. A patient may be administered one medicine at a time or a mixture of drugs at the same time.

Immunotherapy

Immunotherapy is also referred to as biological therapy where the body’s natural immune system is used to fight cancer cells.

Immunotherapy drugs are developed in a laboratory. These drugs are injected into the patients to enhance or restore the body’s natural anti-cancer defenses.

• Interferon is the immunotherapy drug that reduces white blood cells and cells with the Philadelphia chromosome.
• It affects the cellular division of cancer cells and slows down tumor growth.
• Interferon may induce flu-like symptoms such as:
  • Fever and chills
  • Exhaustion
  • Lack of appetite
  • Memory loss
  • Fatigue 

Earlier, interferon was given to treat CML, but with the development of imatinib, interferon is no longer advised as the first-line therapy. This is because studies reported that targeted therapy drugs have fewer side effects while providing better outcomes.

High-dose chemotherapy with stem cell transplant

To destroy cancer cells, high dosages of chemotherapy are administered. However, with cancer therapy, healthy cells are also destroyed, including blood-forming cells.

Stem cell transplantation is a procedure used to replenish blood-forming cells.

Hematopoietic stem cells are immature blood cells that give rise to various mature blood cells and are of two types:

1. Autologous transplant: Stem cells are extracted from the patient’s bone marrow or blood before giving chemotherapy and are stored frozen until reinfusion.
2. Allogenic transplant: Stem cells may be extracted from a donor and infused into the patient.

The stored stem cells are defrosted and infused back into the patient following chemotherapy. These reinfused hematopoietic stem cells develop into healthy bone marrow and blood cells in the body.

Currently, hematopoietic stem cell transfer is widely used rather than a bone marrow transplant that cures CML because bone marrow transplant has several side effects.

Donor lymphocyte infusion (DLI)

DLI is a cancer therapy that is done after a stem cell transplant.

• Lymphocytes are immune cells that belong to white blood cells.
• These lymphocytes are extracted from the stem cells of the donor and are preserved for future use.
• These lymphocytes when infused into the patient recognize and kill the cancer cells considering them as foreign bodies.

Surgery

If other cancer treatments, such as chemotherapy, don’t help cure cancer, the spleen is removed by performing splenectomy.

Although it has no role in cancer treatment, removal reduces the symptoms of an enlarged spleen that occurred due to the blood disorder. Splenectomy may help improve the blood count that reduce the need for blood transfusion.

What is resistant chronic myeloid leukemia?

Chronic myeloid leukemia (CML) that is resistant to therapy is CML that has returned after treatment or does not respond to treatment.

• If CML returns, more tests will be performed to determine the degree of the disease. 
• These tests and scans are frequently identical to those performed at the time of the first diagnosis.

What is palliative care?

Palliative care includes a wide range of interventions, including medication, dietary modifications, relaxation methods, emotional support, and others.

• Palliative care refers to any therapy that aims to alleviate symptoms, improve quality of life, and assist patients and their families.
• Palliative care is available to everybody, regardless of age or type of disease.
• It is most effective when palliative care is initiated as early as possible in the cancer treatment process.

Patients who are frequently treated for leukemia receive palliative treatment at the same time that helps alleviate adverse effects, and such patients have less severe symptoms, a higher quality of life, and are happy with their treatment.