What is Chronic Myelogenous Leukemia (Chronic Cancer of the Cells that Create Blood Cells)?
Chronic myeloid leukemia (CML), where BCR-ABL1 is positive, is a type of blood disorder where there is an increase in immature white blood cells. This condition is identified by the presence of a specific change in chromosomes, also known as the Philadelphia chromosome or translocation t(9;22)(q34;q11.2). Both the peripheral blood stream and the bone marrow, where blood cells are produced, are affected by CML.
What Causes Chronic Myelogenous Leukemia (Chronic Cancer of the Cells that Create Blood Cells)?
Studies show that there’s a higher rate of a type of cancer known as chronic myeloid leukemia (CML) among people who survived atomic bombings. However, it’s not clear what specific factors increase the risk of developing this disease.
Risk Factors and Frequency for Chronic Myelogenous Leukemia (Chronic Cancer of the Cells that Create Blood Cells)
Chronic Myelogenous Leukemia (CML) is a condition that occurs globally with an annual rate of 0.87 cases per 100,000 people. This number tends to rise, reaching 1.52 cases for individuals over 70 years old. Men are slightly more likely to get it than women. The median age for diagnosis is 56 years old.
In the context of the United States, between 2009 and 2013, the annual occurrence rate was 1.4 and 2.2 per 100,000 for women and men, respectively. It was estimated that 2018 saw 8,490 new cases of CML and approximately 1,090 deaths due to the condition.
Signs and Symptoms of Chronic Myelogenous Leukemia (Chronic Cancer of the Cells that Create Blood Cells)
Chronic Myelogenous Leukemia (CML) is a kind of blood cancer often found during routine blood tests, as about half of its patients do not show any obvious symptoms. Most people with CML are usually in the chronic phase when diagnosed. During this phase, patients often show symptoms related to anemia, such as fatigue and malaise, and to enlarged spleen, like early satiety, left upper quadrant fullness, or pain. It could also lead to low platelet count, causing bleeding, or high platelet count resulting in blood clots or priapism. Basophilia, a condition where there is an excessive number of basophils (a kind of white blood cell) in the blood, could lead to histamine release and upper gastrointestinal ulcers. Patients’ symptoms might escalate as CML advances into the accelerated phase or blast phase, with symptoms such as headaches, bone pain, fever, joint pain, bleeding, infections, and swollen lymph nodes becoming more common.
During the physical exam, the doctor typically assesses the size of the spleen by touching the abdomen. Enlarged spleen is the most common physical exam finding in CML patients. In many cases, the spleen size extends beyond 5 cm below the left rib margin at the time of diagnosis. A very large spleen often indicates the disease transitioning into the acute blast crisis stage. An enlarged liver may also be found since it is involved in blood cell production occurring in the spleen. Other physical findings might include signs of thick blood. On examining the back of the eye, there might be signs of pressure on the optic nerve, venous obstruction, and hemorrhages.
- Fatigue and malaise due to anemia
- Early satiety
- Upper abdomen fullness or pain from an enlarged spleen
- Bleeding due to low platelet count
- Blood clots or priapism due to high platelet count
- Upper gastrointestinal ulcers from excessive basophils releasing histamine into blood
- Headaches, bone pain, fever, joint pain, infections, and swollen lymph nodes as CML progresses
- Physical findings of spleen size, possible enlarged liver, signs of thick blood, or changes in the back of the eye
Testing for Chronic Myelogenous Leukemia (Chronic Cancer of the Cells that Create Blood Cells)
If the doctors suspect chronic myeloid leukemia (CML), they may recommend specific blood tests, such as cytogenetic testing, fluorescent in situ hybridization (FISH), and/or reverse transcriptase-polymerase chain reaction (PCR). These tests will look for certain markers such as the Philadelphia chromosome or BCR-ABL1 oncoprotein.
When diagnosing CML, doctors typically perform a comprehensive set of blood tests, including a complete blood count, chemistry panel, and hepatitis panel. In addition, they perform a PCR test for BCR-ABL1 and a bone marrow aspirate and biopsy. The PCR test will be repeated every three months once the treatment starts and then every 3 to 6 months after two years of successful reduction in BCR-ABL1 levels.
Doctors also use a scoring system to determine the risk factor of CML. Two commonly used systems are the Sokal and Hasford risk calculations. The Sokal risk system uses the patient’s age, spleen size, platelet count, and percentage of myeloblasts in the blood. The Hasford risk system uses those factors plus the percentage of eosinophils and basophils in the blood.
In more severe cases of CML, such as the accelerated or blast phase, doctors may also perform tests like flow cytometry to identify the type of cells involved, mutational analysis to detect genetic changes, and HLA testing if a stem cell transplant is being considered. If the treatment doesn’t seem to be working, additional testing of the bone marrow and mutation analysis may be necessary.
Treatment Options for Chronic Myelogenous Leukemia (Chronic Cancer of the Cells that Create Blood Cells)
There are four FDA-approved, front-line treatments for chronic phase Chronic Myeloid Leukemia (CML) that can be obtained. These include a first-generation drug called imatinib, and three second-generation drugs, dasatinib, nilotinib, and bosutinib, which are grouped as tyrosine kinase inhibitors.
How these drugs are taken, dosing, varies:
* Imatinib: 400 mg per day
* Bosutinib: 500 mg per day
* Dasatinib: 100 mg per day
* Nilotinib: 300 mg, two times a day
For chronic phase CML which is at an intermediate or high risk, the second-generation inhibitors (bosutinib, dasatinib, nilotinib) may have more benefits compared to the first generation drug, imatinib.
Ponatinib, a third-generation inhibitor, is used at a dosage of 45 mg daily and is used as a third option in chronic CML treatment. This is for patients who have not seen an improvement after treatment with other tyrosine kinase inhibitors and for those who have a T315I mutation.
In more advanced cases of CML, such as the accelerated or blast phases, other treatment considerations should be made. Second or third-generation inhibitor therapy should be started to reduce the burden of CML, and early allogeneic hematopoic stem cell transplant (HSCT) should be considered. Omacetaxine, a chemotherapy agent, can also be considered for treatment, especially for chronic phase CML cases that resist tyrosine kinase inhibitor therapy.
HSCT should also be considered for patients resistant to tyrosine kinase inhibitor therapy in chronic phase CML, and in cases of advanced CML.
In addition, participation in clinical trials should be considered for all CML patients.
What else can Chronic Myelogenous Leukemia (Chronic Cancer of the Cells that Create Blood Cells) be?
It’s important to distinguish Chronic Myeloid Leukemia (CML) from other conditions that can increase white blood cells, like infections or certain medications. Most times, when the increase in white blood cells is due to these causes, the count is usually less than 50 x 10/L. Also, these cases often show signs like toxic granulation and Dohle bodies, and there’s no increase in basophils, a type of white blood cell.
Other blood disorders like Chronic Neutrophilic Leukemia (CNL) and Polycythemia Vera (PV) can also lead to an increased count of white blood cells and platelets. However, neither CNL nor PV includes a specific gene fusion (BCR-ABL1) that is present in CML. CNL is a rare condition that results in an increased number of mature neutrophils (a type of white blood cell) and won’t show an increased count of myelocytes (young white blood cells) which typically occurs in CML.
What to expect with Chronic Myelogenous Leukemia (Chronic Cancer of the Cells that Create Blood Cells)
Before the introduction of the medical treatment known as imatinib, people commonly experienced a rapidly deteriorating condition with their Chronic Myeloid Leukemia (CML) and would often pass away within five years. But the use of a new treatment called tyrosine kinase inhibitors dramatically improved survival rates. The five-year survival rate shot up from 33% to over 90%, the ten-year survival rate went from 11% to 84%, and 70% to 90% of patients experienced a full cytogenetic response, which means their cells returned to a normal state.
CML patients who get diagnosed during the chronic phase, the first stage of the disease, can expect to live a normal or almost normal lifespan.
Doctors often perform cytogenetic analysis to look for additional abnormalities in the chromosomes, which can provide essential information about the patient’s prognosis. Previously, any extra chromosomal abnormalities were seen as indicators of the disease’s progression, resistance to tyrosine kinase inhibitors, and a worse prognosis. However, recent studies have shown that solitary chromosomal abnormalities involving trisomy 8 (an extra copy of chromosome 8), the loss of the Y chromosome, or an extra copy of the Philadelphia chromosome don’t affect the patient’s survival rate. On the other hand, having two or more additional chromosomal abnormalities or a single additional chromosomal abnormality that includes specific changes are indicators of a poor prognosis.
A patient’s prognosis might also be impacted by BCR-ABL1 mutation analysis. The mutation T315I was found to be associated with resistance to tyrosine kinase inhibitors. More than a hundred other point mutations have been found in patients who are resistant to imatinib, and these mutations can have significant implications for treatment planning.
In the future, prognosis evaluations may include tests for mutations in cancer-related genes such as IKZF1, RUNX1, ASXL1, BCORL1, and IDH1. These mutations were found in patients who developed blast-phase CML, the more severe form of the disease.
Possible Complications When Diagnosed with Chronic Myelogenous Leukemia (Chronic Cancer of the Cells that Create Blood Cells)
Complications from Chronic Myeloid Leukemia (CML) could consist of various health issues, which may include:
- Enlarged liver and/or spleen
- Deteriorating anemia
- Alterations in platelet count, leading to clotting or bleeding problems
- Frequent infections
- Pain in the bones
- Fever
Preventing Chronic Myelogenous Leukemia (Chronic Cancer of the Cells that Create Blood Cells)
After being diagnosed with Chronic Myelogenous Leukemia (CML), patients need to go through certain tests. These tests help to see if the disease has spread and find out what stage it’s at. CML has three stages: chronic, acute, and blastic, and the treatment depends on the stage of the disease. It’s also important for patients to know that the disease could come back even after treatment.
Patients should also understand what to expect and how the disease might affect their future health. This is known as their prognosis, and several aspects can influence it. These include the patient’s age, the stage of the disease, the number of ‘blast’ cells (immature cells) in the blood or bone marrow, the size of the spleen, and the patient’s overall health.
Finally, patients need to be aware of the possible side effects of their treatment and how it might impact their lives. This knowledge helps them make informed decisions about their healthcare and handle any potential side effects better.