Chronic myeloid leukemia (CML)

Definition

Chronic myeloid leukemia is a malignant myeloproliferative disease characterized by a predominant lesion of the granulocytic sprout. It can be asymptomatic for a long time. It is manifested by a tendency to subfebrile fever, a feeling of fullness in the abdomen, frequent infections, and spleen enlargement. Anemia and changes in platelet levels are observed, accompanied by weakness, pallor, and increased bleeding. In the final stage, fever, lymphadenopathy, and skin rash develop. Diagnosis is established by considering the anamnesis, clinical picture, and laboratory test data. Treatment – chemotherapy, radiotherapy, bone marrow transplantation.

General information

Chronic myeloid leukemia is a cancer resulting from a chromosomal mutation involving polypotent stem cells and subsequent uncontrolled proliferation of mature granulocytes. It accounts for 15% of all adult hemoblastosis and 9% of all leukemia in all age groups. Usually develops after the age of 30 years, the peak incidence of chronic myeloid leukemia is between the ages of 45-55 years. Children under ten years of age are exceptionally rarely affected.

Chronic myeloid leukemia is equally common in women and men. Because of its asymptomatic or mildly asymptomatic course, it may become an incidental finding during a blood test taken in connection with another disease or during a routine checkup. In some patients, chronic myeloid leukemia is detected in the final stages, which limits therapy options and worsens survival rates. Treatment is provided by specialists in oncology and hematology.

Reasons

Chronic myeloid leukemia is considered to be the first disease in which a link between the development of pathology and a specific genetic disorder has been reliably established. In 95% of cases, the confirmed cause of chronic myeloid leukemia is a chromosomal translocation known as the “Philadelphia chromosome.” The essence of the translocation is the mutual replacement of parts of chromosomes 9 and 22. As a result of such replacement, a stable open reading frame is formed. The formation of the frame causes the acceleration of cell division and inhibits the DNA repair mechanism, which increases the likelihood of other genetic anomalies.

Ionizing radiation and contact with certain chemical compounds are among the possible factors contributing to the Philadelphia chromosome in patients with chronic myeloid leukemia.

Symptoms of chronic myeloid leukemia

The stage of the disease determines the clinical picture. The chronic phase lasts, on average, 2-3 years, sometimes up to 10 years. This phase of chronic myeloid leukemia is characterized by an asymptomatic course or gradual appearance of “light” symptoms: weakness, some malaise, decreased ability to work, and a feeling of overflowing abdomen. Objective examination of a patient with chronic myeloid leukemia may reveal an enlarged spleen. Blood tests reveal an increase in the number of granulocytes up to 50-200 thousand /μL in the asymptomatic course of the disease and up to 200-1000 thousand /μL in “mild” signs.

In the initial stages of chronic myeloid leukemia, there may be some decrease in hemoglobin levels. Subsequently, normochromic normocytic anemia develops. When examining the blood smear of patients with chronic myeloid leukemia, the predominance of young forms of granulocytes is noted: myelocytes, promyelocytes, and myeloblasts. Deviations from the normal level of granularity in one or the other direction (abundant or very scarce) are observed. The cytoplasm of cells is immature and basophilic. Anisocytosis is determined. In the absence of treatment, the chronic phase progresses to the accelerated phase.

A blast crisis is accompanied by a sharp deterioration in the condition of a patient with chronic myeloid leukemia. New chromosomal abnormalities arise, and monoclonal neoplasm is transformed into polyclonal. There is an increase in cellular atypia with suppression of regular hematopoietic sprouts. There are pronounced anemia and thrombocytopenia. The total number of blasts and promyelocytes in the peripheral blood is more than 30%, and in the bone marrow – more than 50%. Patients with chronic myeloid leukemia lose weight and appetite. Extramedullary foci of immature cells (chloromas) appear. Bleeding and severe infectious complications develop.

Diagnosis

Diagnosis is based on clinical presentation and laboratory findings. The first suspicion of chronic myeloid leukemia is often raised by an elevated granulocyte count in a general blood test ordered as a preventive examination or in connection with another disease. Histologic examination of bone marrow sternal puncture material may clarify the diagnosis, but a definitive diagnosis of chronic myeloid leukemia is made when the Philadelphia chromosome is detected by PCR, fluorescent hybridization, or cytogenetic testing.

The question of whether a diagnosis of chronic myeloid leukemia can be made in the absence of the Philadelphia chromosome remains controversial. Many researchers believe that such cases may be due to complex chromosomal abnormalities that make it difficult to detect this translocation. In some cases, the Philadelphia chromosome can be detected using reverse transcription PCR. In the case of negative results and atypical course of the disease, it is usually not chronic myeloid leukemia but undifferentiated myeloproliferative/myelodysplastic disorder.

Treatment of chronic myeloid leukemia

Treatment tactics are determined depending on the phase of the disease and the severity of clinical manifestations. They are limited to general tonic measures in the chronic phase with an asymptomatic course and poorly expressed laboratory changes. Patients with chronic myeloid leukemia are recommended to observe the regime of labor and rest, take food rich in vitamins, etc. Treatment may include:

• Monochemotherapy. If the leukocyte level rises, busulfan is used. After normalizing laboratory parameters and reducing the spleen, patients with chronic myeloid leukemia are prescribed maintenance therapy or course treatment with busulfan. In blast crises, treatment with hydroxycarbamide is carried out.
• Radiotherapy. Radiation is usually used when leukocytosis is combined with splenomegaly. If the leukocyte count decreases, a pause of at least one month is made, and then maintenance therapy with busulfan is switched. Radiotherapy is also prescribed for chloromas.
• Polychemotherapy. In the advanced phase of chronic myeloid leukemia, a single chemical agent or polychemotherapy may be used. As in the chronic phase, intensive therapy is carried out until laboratory parameters are stabilized and maintenance doses are prescribed. Courses of polychemotherapy in chronic myeloid leukemia are repeated 3-4 times a year.
• Bone marrow transplantation is performed in the first phase of chronic myeloid leukemia. Prolonged remission can be achieved in 70% of patients.
• Removal of the spleen. If indicated, splenectomy is performed. Emergency splenectomy is indicated in case of rupture or threat of rupture of the spleen, planned – in hemolytic crises, recurrent perisplenitis and sharply pronounced splenomegaly, accompanied by dysfunction of abdominal cavity organs.

All these treatment options are available in more than 700 hospitals worldwide (https://doctor.global/results/diseases/chronic-myeloid-leukemia-cml). For example, Splenectomy can be done in 12 clinics across Turkey for an approximate price of $6.3 K (https://doctor.global/results/asia/turkey/all-cities/all-specializations/procedures/splenectomy). 

Prognosis

The prognosis in chronic myeloid leukemia depends on many factors, the most important of which is the moment of treatment initiation (in the chronic phase, activation phase, or during the blast crisis). Significant enlargement of the liver and spleen (liver protrudes from under the edge of the rib arch by six or more cm, spleen – by 15 or more cm) are considered unfavorable prognostic signs of chronic myeloid leukemia, leukocytosis more than 100×10⁹ /L, thrombocytopenia less than 150×10⁹ /L, thrombocytosis more than 500×10⁹ /L, increase in the level of blast cells in peripheral blood up to 1% or more, increase in the total level of promyelocytes and blast cells in peripheral blood up to 30% or more.

The likelihood of an unfavorable outcome in chronic myeloid leukemia increases as the number of signs increases. The cause of death is infectious complications or severe hemorrhages. The average life expectancy of patients with chronic myeloid leukemia is 2.5 years, but with timely initiation of therapy and a favorable course of the disease, this indicator can increase to several tens of years.