Leukemia is the tenth most common cancer constituting about 3.5% of all cancers in the United States (US).
Leukemia is divided into four main types:
Chronic myeloid leukemia (CML) accounts for about 1.5% of all leukemia cases, about 0.5% of all new cancers, and about 0.2% of all cancer-related deaths in the US. The overall incidence rate of CML has been slightly increasing while the mortality rate of CML has been declining during the last decade.
CML more commonly affects older age individuals with highest incidences observed in individuals aged between 65 to 74 years. The incidence rate of CML is slightly higher in males than in females.
The blood is a connective tissue consisting of a liquid extracellular matrix (the plasma) and suspended formed elements (comprising blood cells and cell fragments). The 3 main components of formed elements include red blood cells (RBCs), white blood cells (WBCs) and platelets.
The WBCs are further divided into various subtypes based on their appearance under the microscope (with the application of different staining): neutrophils, basophils, eosinophils, monocytes, and lymphocytes (T-cells, B-cells, and natural killer cells). Each type of blood cell has a distinct function and is produced from pluripotent stem cell in the red bone marrow by a process called hemopoiesis.
CML is a disorder in which myeloid blasts (precursor of myeloid cells) start dividing without control. This is postulated to be caused by a genetic change (reported in more than 95% of all CML patients) in the immature myeloid cells, which is referred to as Philadelphia chromosome (Ph) – a reciprocal translocation between chromosomes 9 and 22 [t(9;22] that gives rise to a BCR-ABL1 fusion gene.
The fusion gene gives rise to a protein with deregulated tyrosine kinase activity that turns the cells to CML cells (the abnormal myeloid precursors with Ph+), which divide indefinitely and get crowded in the red bone marrow and peripheral blood causing a reduction in the number of normal blood cells. Characteristically, CML is a slow-growing disorder which is mostly diagnosed in chronic phase, which may become aggressive (progressed to accelerated or blast phase) if not treated appropriately.
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Not many risk factors have been identified for CML. Following is the list of such risk factors:
Following are some common signs and symptoms of CML:
If a person is suspected to have CML, some investigations are required to confirm the diagnosis of the disease. Further, these investigations can help in determining the phase of CML, organ involvement, cytogenetic abnormalities, etc. which in turn help in selecting an appropriate treatment approach.
Following are some commonly used diagnostic tools for CML:
Based on the clinical manifestations, CML can occur in following three phases:
Following 2 systems are used to stratify the patients with CML in different risk groups:
The treatment of CML depends on many factors, including but not limited to, the phase of the disease, risk group, associated comorbidities (to choose the drugs which do not have similar side effects), and performance status of the patient.
Following are the preferred treatment approaches for different phases of CML, but the final decision is taken after clinical assessment of the patient by an oncologist.
|PHASE OF CML||TREATMENT|
|Chronic Phase (CP) CML||
In low-risk patients, both first-generation and second-generation tyrosine kinase inhibitors (TKIs) are considered as the standard treatment; however, in case of intermediate to high-risk patients, second-generation TKIs are considered the preferred treatment.
After starting the treatment, RT-PCR is done at regular intervals to assess the response to treatment. Further decision whether to continue the same drug or change the treatment is taken depending on the response.
|Accelerated Phase (AP) CML||
In patients with newly diagnosed accelerated phase CML, TKI therapy is considered the preferred treatment.
In case of patients with chronic phase CML who have progressed to accelerated phase, mutational analysis is done to check for resistance. Thereafter, a different TKI is used that is active against the mutation detected. Allogeneic SCT can be considered in case of mutations resistant to TKIs.
|Blast Phase (BP) CML||
In patients with newly diagnosed blast phase CML, induction treatment for ALL or AML is given, depending upon whether it’s lymphoid or myeloid blast crisis, respectively. Allogeneic SCT is indicated once patient has attained CR after induction. TKI is given throughout along with chemotherapy and continued thereafter.
In case of patients whose disease has progressed from CP or AP to blast phase, induction treatment for ALL or AML is given, depending upon whether it’s lymphoid or myeloid blast crisis, respectively. Allogeneic SCT is indicated once patient has attained CR after induction. Mutational analysis is done to check for resistance. Thereafter, a different TKI is used that is active against the mutation detected. TKI is given throughout along with chemotherapy and continued thereafter.
Following is a brief description of various treatment types employed for CML:
It is very important to assess the benefits of each treatment option versus the possible risks and side effects before making a treatment decision. Sometimes patient’s choice and health condition are also important to make a treatment choice.
Following are the goals of treating CML:
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