Overview
Chronic myeloid leukemia (CML) is a malignancy that affects the bone marrow and blood. In CML, the bone marrow creates an excess of granulocytes, which are white blood cells. These cells (also referred to as blasts or leukemic blasts) eventually overrun the bone marrow, inhibiting the generation of normal blood cells. In addition, they leak from the bone marrow and circulate throughout the body via the bloodstream. Due to their immaturity, they are unable to effectively fend off infections. A deficiency of red cells and platelets can result in anemia, bleeding, and/or bruising over time.
Acute vs Chronic Myeloid Leukemia
Unlike acute myeloid leukemia (AML), CML takes longer to develop. The majority of CML patients can live for many years. Rarely, CML can transform into acute leukemia, which requires prompt medical care. Importantly, some people with acute leukemia (particularly acute lymphocytic leukemia) contain the Philadelphia chromosome but may not develop CML. CML and ALL with the Philadelphia chromosome are treated differently, while some treatments overlap.
CML causes
- CML is caused by a genetic alteration (mutation) in the bone marrow stem cells.
- The mutation leads stem cells to produce an excessive number of immature white blood cells. It also decreases the number of other blood cells, including red blood cells.
- The alteration involves DNA structures known as chromosomes. Within each stem cell, DNA from one chromosome is exchanged for DNA from another. This variation is referred to as the “Philadelphia chromosome.” Learn more about chromosomes and genes.
- It is unknown what causes this, however, it is not a genetic trait and cannot be passed on to future generations.
Risk factors for CML
The following factors may raise the likelihood of having CML, according to scientists:
- Radiation exposure – CML is more prevalent in individuals exposed to high doses of radiation.
- Age – CML is more prevalent in older than in younger individuals.
- Gender – CML is significantly more prevalent in men than in women.
Chronic Myeloid Leukemia Phases
There are three distinct CML stages. The phases are determined by the number of immature blood cells (blast cells) in the patient’s blood or bone marrow. The CML stages are known as:
- Chronic Phase CML: This is the phase in which the majority of patients are initially diagnosed with leukemia. Symptoms are less severe during this phase. After initiating treatment for leukemia, individuals can typically resume their normal daily activities. Less than 10 percent of blood and bone marrow cells are blast cells.
- Accelerated Phase CML: Individuals in this phase may have a depleted red blood cell count. This is known as anemia. The amount of blast cells is greater than during the chronic phase (about 10 percent – 19 percent ). These cells may expand more rapidly than during the chronic period. In this phase, individuals may feel unwell.
- Blast Crisis Phase CML: Similar to acute leukemia, this phase is characterized by a high number of immature blast cells in the bone marrow and blood. Red blood cells, white blood cells, and platelets may be in insufficient supply. This may result in anemia, excessive bleeding, or infections. Also possible are shortness of breath and bone discomfort. As in acute leukemia, leukemia cells tend to multiply rapidly. More than twenty percent of blood and bone marrow cells are blast cells.
Symptoms of Chronic Myeloid Leukemia
As malignant cells flood the spleen and bone marrow and drive out healthy blood cells, the first symptoms of chronic myeloid leukemia appear. This leads in low red blood cell and platelet counts and elevated white blood cell levels. The onset of symptoms is slow and may include:
- Fever
- Fatigue and frailty
- Problems breathing
- Looking pale
- Extreme bruising or blood loss
- Night perspiration
- Soreness and aches in the bones
- Pain or enlargement on the left side of the abdomen resulting from an enlarged spleen
Diagnostic testing
CML is typically detected during a routine blood count. If your doctor feels you may have CML, he or she will order more tests to confirm your diagnosis. These tests may consist of:
- A physical examination: Your healthcare practitioner will assess your vital signs and palpate your belly and lymph nodes to detect any strange sensations.
- Bone marrow biopsy: Samples of bone marrow are extracted, typically from the hip bone, and sent to a pathology laboratory for analysis.
- FISH analysis (fluorescence in situ hybridization): This test uses fluorescence to detect and pinpoint genetic material in your cells.
- PCR (polymerase chain reaction) test: PCR can duplicate a DNA segment millions of times. This is useful when more assessments are required.
Treatment
The purpose of your treatment is to eradicate the leukemia blood cells in your body and return the healthy blood cell count to normal. Typically, it is impossible to eliminate all harmful cells. If you receive treatment at the early, chronic phase of CML, it can delay the progression of the disease to a more severe stage. Typically, tyrosine kinase inhibitors (TKIs) are used initially. They slow down the body’s production of leukemia cells.
Examples of commonly used TKIs include:
- Bosutinib (Bosulif)
- Dasatinib (Sprycel)
- Imatinib (Gleevec)
- Nilotinib (Tasigna)
Bosutinib (Bosulif) and ponatinib (Iclusig) may be prescribed if other medications are ineffective or make you too ill.
If your condition worsens despite the use of two or more TKIs, your physician may recommend asciminib (Scemblix) or omacetaxine mepesuccinate (Synribo).
Other treatment options for CML include chemotherapy and biologic therapy, which employs interferon to stimulate the immune system — the body’s protection against pathogens.
A stem cell transplant might treat some individuals. It is a complex technique that is often performed only when other therapies have failed. Stem cells are frequently mentioned in the media, although typically, they relate to “embryo” stem cells that are employed in cloning. Different stem cells are used in a stem cell transplant. These cells reside in the bone marrow and aid in the production of new blood cells.
When receiving a stem cell transplant, the new stem cells will come from a donor. So that your body does not “reject” the donor, you will need to be placed on a waiting list to find a compatible donor.
Close relatives, such as your brother or sister, offer the most potential for a successful relationship. If that does not work, you must add yourself to a list of possible donors from the general public. Sometimes you have the highest chance of receiving the correct stem cells from someone of the same race or ethnicity as you.
When should I consult a transplant physician?
You should consult a transplant physician if:
- The CML does not improve with regular therapy. The majority of people with CML take TKIs (tyrosine kinase inhibitors). These medications may suppress CML for several months or years.
- The CML worsens regardless of therapy with TKIs
- You cannot use TKIs due to serious adverse reactions or an allergy.
- The CML is accelerating or in the blast phase
Prognosis
Over the past two decades, CML survival rates have increased considerably due to TKI treatment.
CML has a favorable prognosis for the majority of patients, especially those identified during the chronic phase.
Poor prognostic factors:
- Being in the period of acceleration or detonation
- Osteoporosis brought on by leukemia
- Having an enlarged spleen
- Blood samples with a high concentration of eosinophils and basophils
- Extremely low or high platelet counts
- Being at least 60 years old
- CML cells having many chromosomal alterations
