Most of patients with chronic myelogenous leukemia are diagnosed in the chronic phase and then progress to the accelerated and blast phases in 3 to 5 years.

The diagnosis of chronic myeloid leukemia is based on the histopathologic findings in the peripheral blood and the presence of the Philadelphia chromosome in bone marrow cells [2] [4].

The clinical symptomatology of chronic myelogenous leukemia may be insidious. The disease is often discovered with routine blood work in the chronic phase, when an elevated white blood cell (WBC) count is revealed or when an enlarged spleen is found in a general physical examination.

The symptoms change as the disease progresses from chronic, to accelerated, and finally to blast.

Signs and symptoms in the chronic phase are [2]:

• Fatigue, weight loss, loss of energy, decreased exercise tolerance
• Low-grade fever and excessive sweating
• Elevated white blood cell (WBC) count
• Splenomegaly
• Decreased appetite and food intake
• Left upper quadrant abdominal pain from splenomegaly
• Hepatomegaly

Signs and symptoms of progressive disease [2] [3]:

• Bleeding, petechiae, and ecchymoses
• Bone pain and fever
• Increasing anemia, thrombocytopenia, basophilia,
• Rapidly enlarging spleen

The manifestations of blast crisis are similar to those of acute leukemia. Treatment is ineffective in this stage, and most patients succumb to the disease once they reach this phase and survival is 3-6 months.

The diagnosis of chronic myeloid leukemia is based on the following [2]:

• Histologic findings in the peripheral blood
• Philadelphia (Ph) chromosome in bone marrow cells [4]

The workup for chronic myeloid leukemia should include the following [2]:

Complete blood count with differential

• Total white blood cell count - 20,000-60,000 cells/μL
• Increased basophils and eosinophils
• Mild to moderate anemia

Peripheral blood smear [2]

• Leukocyte alkaline phosphatase - absent in most cells
• Immature myeloid cells
• Leukoerythroblastosis, with circulating immature cells

Bone marrow analysis [2] [4]

• Philadelphia chromosome present - transposition of chromosomal material between chromosomes 9 and 22
• Elevated cell counts of neutrophils, eosinophils, and basophils
• Megakaryocytes are prominent and may be increased
• Mild reticulin fibrosis

The goals of treatment of chronic myeloid leukemia are to achieve hematologic, cytogenetic, and molecular remission. Although a variety of medications have been used in chronic myeloid leukemia, including myelosuppressive agents and interferon alfa, the tyrosine kinase inhibitor, imatinib mesylate, is currently the drug of choice [7].

Other drugs in this category are increasingly used [8]. Some patients with molecular remissions from interferon alfa and imatinib may be cured, but this can only be established over time [3] [5] [9].

Allogeneic bone marrow transplantation is currently the only proven cure for chronic myeloid leukemia [8]. Bone marrow or stem cell transplantation are investigative therapies at present used only for younger patients and are extremely expensive.
New agents that are currently under research may prolong the survival of patients with chronic myeloid leukemia and may even offer the possibility of eventual cure [8] [9].

In October 2012, the US Food and Drug Administration (FDA) approved omacetaxine (Synribo). Omacetaxine is a protein translation inhibitor that is indicated in the accelerated phase of patients with chronic myeloid leukemia resistant to or intolerant to 2 or more tyrosine kinase inhibitors [10].

Leukapheresis, using a cell separator, can lower white blood cell counts rapidly and safely. It is used in patients with white blood cell counts greater than 300,000 cells/µ and can alleviate acute symptoms [8].

Splenectomy and splenic irradiation have been used in patients with large and painful spleens, usually in the later phases of chronic myeloid leukemia [8]. Splenectomy is associated with a high incidence of post-operative complications, morbidity, and mortality.

In the past, patients with chronic myeloid leukemia had a median survival rate of 3-5 years from the time of diagnosis. New therapeutic agents have resulted in improvement in survival.

Currently, patients have a median survival of 5 or more years, 50-60% of patients survive at least 5 years. The improvement has resulted from earlier diagnosis, improved therapy with interferon, bone marrow transplantation, and better supportive care [5].

Some patients with remissions from interferon alfa, may be cured, but this can only be proven over time [5] [6].

Chronic myeloid leukemia is caused by a single, specific genetic mutation. More than 90% of cases result from a mutation of a gene responsible for cell production known as the Philadelphia chromosome [3].

Causes for the mutation are not fully known, though exposure to radiation and toxic chemicals is strongly suspected.

Chronic myeloid leukemia accounts for 20% of all leukemias affecting adults [2]. It usually affects the middle-aged, uncommonly, occurring in younger individuals.

Younger patients may have a more aggressive form of chronic myeloid leukemia, presenting in the accelerated phase or in blast crisis.

Chronic myeloid leukemia is an acquired abnormality that involves the hematopoietic stem cells. It is characterized by an abnormality that causes a reciprocal translocation of the long arms of chromosomes 22 and 9 [1] [3].

The translocation results in a shortened chromosome 22, first noted by Nowell and Hungerford in Philadelphia and named the Philadelphia (Ph1) chromosome after the city where it was discovered [2] [3].

The resulting gene forms a mutant protein with strong tyrosine kinase activity. The manifestation of this protein causes the development of chronic myeloid leukemia through processes that are not yet fully understood [2] [3] [4].

The cause of chronic myeloid leukemia is still unknown, but exposure to ionizing radiation is suspected. It was observed among survivors of the atomic bombing of Hiroshima and Nagasaki. Other agents, such as benzene, are also possible causes [2].

There are no guidelines for prevention of chronic myeloid leukemia.

Chronic myeloid leukemia is a bone marrow stem cell disorder characterized by increased production of the granulocytic white blood cells and decreased hematopoiesis leading to cytopenia.

Chronic myeloid leukemia progresses through 3 phases: chronic, accelerated, and blastic. In the chronic phase of the disease most white blood cells are mature. In the accelerated phase additional cell abnormalities occur. In the blast phase immature cells proliferate rapidly, crowding out normal cells.

Prolonging survival is the primary goal of therapy. Allogeneic stem cell transplantation (SCT) remains the only curative treatment, but is rarely used in elderly patients [1] [2].

What is chronic myeloid leukemia?

Chronic myeloid leukemia is a slowly progressing form of blood cancer. It interferes with the production of blood cells in the bone marrow, where blood cells are made. As a result your body makes too many abnormal, immature white blood cells, called blast cells. Healthy white blood cells help to fight infection. The abnormal cells can no longer perform this function.

In chronic myeloid leukemia the bone marrow makes a greatly increased numbers of abnormal blast cells. These immature cells live longer than normal cells. They crowd out healthy white blood cells, and also red blood cells and platelets (responsible for clotting) as well.

What are the symptoms of chronic myeloid leukemia?

Chronic myeloid leukemia has three phases: chronic, accelerated, and blastic. Chronic-phase chronic myeloid leukemia is the earliest phase and the easiest to treat. The individual may have no symptoms at all.
In the accelerated phase, the number of abnormal blood cells increases. Some or all of these symptoms may be present:

• Fatigue
• Fever
• Bruising
• Night sweats
• Shortness of breath
• Unexplained weight loss
• Appetite loss
• Swelling or pain on your left side (which could be a sign of an enlarged spleen)
• Bone pain

What causes chronic myeloid leukemia?

The exact cause of chronic myeloid leukemia is not known. It starts when a new chromosome, called the Philadelphia chromosome, is formed by the switching of the DNA between two chromosomes (9 and 22).

This new gene tells blood cells to make a new protein which causes the body to begin making too many abnormal, or immature, white blood cells, leaving less room for healthy blood cells and platelets.

Who gets chronic myeloid leukemia?

Anyone can get chronic myeloid leukemia; however, it usually affects middle-aged or older adults. It rarely occurs n children. It happens more frequently in men and those exposed to radiation and certain chemicals.

Family history is not a risk factor. The chromosome mutation that leads to chronic myelogenous leukemia is not passed from parents to their children. This mutation is believed to be acquired, meaning it occurs after birth.

How is chronic myeloid leukemia diagnosed?

Chronic myeloid leukemia is diagnosed using blood tests that show the type and number of the various blood cells, especially white blood cells. Diagnosis is confirmed by biopsy (sampling) of the bone marrow when the presents of a mutated chromosome, called the Philadelphia chromosome, is found.

How is chronic myeloid leukemia treated?

Once a diagnosis of chronic myeloid leukemia is made the goal of treatment is to prevent the progression of the disease as long as possible. Best treatment should include a referral to and evaluation by a doctor with special training in blood diseases/cancers (hematologist-oncologist).

The goal is to stay in the chronic phase and remain symptom-free.
Chronic myelogenous leukemia is a disease that most patients will continue treatment for the rest of their lives.

Treatment of chronic myeloid leukemia is aimed at destroying the abnormal blood cells and restoring normal white blood cells to normal levels.

Diagnosis and treatment beginning in the early, chronic phase of the disease can slow and even prevent the disease from moving to a more serious level.

Medications known as tyrosine kinase inhibitors are usually the first form of treatment. They slow down the production of abnormal white cells.

Other treatment options include chemotherapy, to destroy the abnormal white blood cells, and with interferon which decreases the production of white blood cells. A stem cell transplant from a matching donor may be curative but it is difficult to obtain a match and the procedure is very expensive. It is usually used only when other treatments have failed.

What are the complications of chronic myeloid leukemia?

Complications of chronic of chronic myeloid leukemia may include the following:

• Fatigue due to anemia (decreased number of red blood cells).
• Excessive bleeding and bruising because the number of platelets (blood cells that help control clotting) is decreased.
• Bone pain or joint pain because of expansion of the bone marrow from the buildup of white blood cells.
• Swollen or enlarged spleen due to the e storage of the extra blood cells in the spleen.
• Infection is a significant risk because abnormal white blood cells are not able to fight off infection.
• Death will occur if chronic myeloid leukemia cannot be successfully treated.

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