Chronic Myelogenous Leukemia (CML)

Chronic myelogenous leukemia (CML) is a cancer that grows from cells that produce white blood cells and starts inside the bone marrow. It is also known as chronic granulocytic leukemia (CGL). It is a myeloproliferative disorder symbolized by increased production of the granulocyte cell line without the loss of their ability to separate. Subsequently, the peripheral blood cell profile shows a larger number of granulocytes (neutrophils, eosinophils, and basophils) and their undeveloped precursors, including occasional blast cells. Chronic myelogenous leukemia is a clonal bone marrow stem cell disease associated with a characteristic chromosomal translocation called the Philadelphia chromosome, named after the city where it was discovered.
This form of leukemia tends to affect older males, and more than 90% of cases are due to a gene abnormality caused when two chromosomes switch sections with each other. Humans have 23 chromosomes. In patients that have CML chromosomes 9 and 22 inside blood cells exchange traces of genetic material to form a Philadelphia chromosome. A protein called tyrosine kinase, formed by the new gene on this chromosome, allows white blood cells to grow out of control. The bone marrow where platelets and red and white blood cells are made becomes filled with white blood cells. The white blood cells crowd out the normal cells and damage the bone marrow itself which can weaken the ability to produce normal amounts of blood cells.
CML progresses through 3 phases: chronic, accelerated, and blast crisis.
The chronic phase can last for months or years. In this phase the mature cells proliferate but the patient may have few or no symptoms. This is the stage where approximately 85% of patients are diagnosed when they are having blood tests done for other reasons. The accelerated phase is much more dangerous because the leukemia cells grow more quickly and more cytogenetic abnormalities occur. This phase may be associated with fever, swollen spleen, and bone pain. If untreated, CML advances to the blast crisis phase where immature cells rapidly produce. Infection and bleeding may occur due to bone marrow
failure.
Early symptoms of CML include fever without infection, chills, sweating, and fatigue. Due to the decreasing function of bone marrow in later stages joint and bone pain may occur as the bone marrow pressure increases. This is due to an overload of white blood cells. Anemia may cause fatigue because not enough red blood cells are being produced. Bleeding can also occur if not enough platelets are being made. Strokes can occur in some CML patients due to their bone marrow making too many platelets which causes abnormal blood clotting. The overabundance of white cells in chronic myelogenous leukemia tends to not function properly and their ability to fight infection is compromised. This leads to an increased risk of infection. The oversupply of white blood cells leak out of the bone marrow and circulate in the blood stream eventually becoming trapped in the spleen causing it to enlarge. Other symptoms of CML include: easy bleeding, feeling run down or tired, unintentional weight loss, pale skin, loss of appetite, pain or fullness below the ribs on the left side, and sweating excessively during sleep.
The diagnosis of CML is usually through a blood test called a complete blood count (CBC). A CBC measures the type, number, and characteristics of platelets and red and white blood cells. Abnormal numbers of cells being produced are noted on a smear under a microscope, thus the diagnosis of CML or AML. Basophils and eosinophils are almost universally increased. Bone marrow from a patient’s hip bone examines the area where the cells are made to test for the presence of the Philadelphia chromosome. This characteristic chromosomal abnormality can be discovered by routine cytogenetics, by fluorescent in situ hybridization, or by PCR for the bcr-abl fusion gene.
CML accounts for 20% of all leukemia’s affecting adults and typically affects middle aged individuals. It is uncommon in younger individuals, although some may present with a more aggressive form such as accelerated phase (AML) or blast crisis. Chronic myelogenous leukemia is treatable with drugs that target the abnormal enzyme responsible for the defective white blood cells. Gleevec, Sprycel, and Tasigna shut down the tyrosine kinase enzyme and can keep chronic myelogenous leukemia in remission. The patient will likely need to the medication throughout their lifetime once it is started. If the leukemia redevelops, a bone marrow transplant is the next treatment option. The transplant has a long-term cure rate of 60%-80%. The goals of treatment are to achieve cytogenetic, hematologic, and molecular remission. A variety of medications can be used to treat CML, including myelosuppressive agents and interferon alfa. Imatinib mesylate, a tyrosine kinase inhibitor, is currently the agent of choice, and other drugs in this category are playing increasingly important roles.
After diagnosis of chronic myelogenous leukemia in the chronic phase the disease progresses to accelerated and blast crisis phases after 3 to 5 years. “Currently, patients with CML have a median survival of 5 or more years and a 5-year survival rate of 50-60%. The improvement has resulted from earlier diagnosis, improved therapy with interferon and bone marrow transplantation, and better supportive care.” (Emmanuel C Besa, MD) The annual incidence of CML in the United States is approximately 4800 cases. The annual mortality rate was reduced to 2% with the success of tyrosine kinase inhibitor therapy.
The “chronic” in chronic myleogenous leukemia indicates that this type of cancer tends to progress more slowly than that of acute myelogenous leukemia (AML).
“Acute” indicates the leukemia’s rapid progression. AML is the most common leukemia affecting adults and increases with age. This form of leukemia accounts for approximately 1.2% of cancer deaths in the United States. Patients have an increased risk for AML if they have had a weakened immune system due to an organ transplant, blood disorders (polycythemia vera, essential thrombocythem, & myelodysplasia), or an exposure to radiation and chemicals. Approximately 500 children are diagnosed with acute myeloid leukemia in the United States each
year.
Symptoms of AML include: Bleeding from the nose, bleeding gums, bruising, bone pain or tenderness, fatigue, fever, heavy menstrual periods, pallor, shortness of breath, skin rash or lesion, swollen gums, and weight loss. These symptoms are caused by replacement of normal bone marrow with leukemic cells. This results in a drop in red and white blood cells and platelets. Patients with AML become more prone to infections and have an increased risk for bleeding as the numbers of healthy blood cells decrease. AML progresses very rapidly and is fatal in weeks to months if untreated. Acute myeloid leukemia is treated initially with chemotherapy intended to induce remission, although some patients may need to receive a hematopoietic stem cell transplant.
An estimated 44,600 new cases of leukemia was expected in 2011. Leukemia is classified into four groups according to cell type: acute myeloid (AML), chronic lymphocytic (CLL), acute lymphocytic (ALL), and chronic myelogenous (CML). “Almost 90% of leukemia cases are diagnosed in adults 20 years of age and older, in whom the most common types are AML and CLL. Since 1992, leukemia incidence rates overall have been stable in males and increasing slightly (0.5% per year) in females.” (American Cancer Society) Death rates for leukemia have declined by 0.9% since 2003 in men and a 1.6% decrease in women. References
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Emmanuel C Besa, M. (n.d.). Chronic Myelogenous Leukemia. Retrieved from http://emedicine.medscape.com/article/199425-overview#aw2aab6b2b3aa
Encyclopedia, A. M. (n.d.). Acute myeloid leukemia. Retrieved from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001569/
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Staff, M. C. (n.d.). Chronic myelogenous leukemia. Retrieved from http://www.mayoclinic.com/health/chronic-myelogenous-leukemia/DS00564/DSECTION=treatments-and-drugs