Chronic myeloid leukemia is a malignant myeloproliferative disease characterized by a predominant lesion of the granulocytic germ. It can be asymptomatic for a long time. It is manifested by a tendency to subfebrility, a feeling of fullness in the abdomen, frequent infections and an increase in the spleen. 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. The diagnosis is made taking into account the anamnesis, clinical picture and laboratory data. Treatment – chemotherapy, radiotherapy, bone marrow transplantation.
Chronic myeloid leukemia is an oncological disease resulting from a chromosomal mutation with damage to polypotent stem cells and subsequent uncontrolled proliferation of mature granulocytes. It accounts for 15% of the total number of hemoblastoses in adults and 9% of the total number of leukemias in all age groups. Usually develops after 30 years, the peak incidence occurs at the age of 45-55 years. Children under 10 years of age suffer extremely rarely.
Disease is equally common in women and men. Due to an asymptomatic or low-symptomatic course, it may become an accidental finding when examining a blood test taken in connection with another disease or during a preventive examination. In some patients, pathology is detected in the final stages, which limits the possibilities of therapy and worsens survival rates. The treatment is carried out by specialists in the field of oncology and hematology.
Chronic myeloid leukemia is considered the first disease in which a reliable link between the development of pathology and a certain genetic disorder has been established. In 95% of cases, the confirmed cause is a chromosomal translocation known as the “Philadelphia chromosome”. The essence of translocation is the mutual replacement of sections 9 and 22 of chromosomes. As a result of such a replacement, a stable open reading frame is formed. The formation of a frame causes an acceleration of cell division and suppresses the DNA repair mechanism, which increases the likelihood of other genetic abnormalities.
Among the possible factors contributing to the appearance of the Philadelphia chromosome in patients with this disease, ionizing radiation and contact with certain chemical compounds are called.
The mutation results in increased proliferation of polypotent stem cells. In chronic myeloid leukemia, mainly mature granulocytes proliferate, but the abnormal clone includes other blood cells: erythrocytes, monocytes, megakaryocytes, less often – B- and T-lifocytes. Normal hematopoietic cells do not disappear at the same time and after the suppression of an abnormal clone can serve as the basis for normal proliferation of blood cells. Chronic myeloid leukemia is characterized by a stage course.
- In the first, chronic (inactive) phase, there is a gradual aggravation of pathological changes while maintaining a satisfactory general condition.
- In the second phase of chronic myeloid leukemia – the acceleration phase, changes become apparent, progressive anemia and thrombocytopenia develop.
- The final stage of chronic myeloid leukemia is a blast crisis, accompanied by rapid extramedullary proliferation of blast cells.
The source of blasts are lymph nodes, bones, skin, central nervous system, etc. In the phase of a blast crisis, the condition of a patient with chronic myeloid leukemia deteriorates sharply, severe complications develop, culminating in the death of the patient. In some patients, there is no acceleration phase, the chronic phase is immediately replaced by a blast crisis.
Chronic myeloid leukemia symptoms
The clinical picture is determined by the stage of the disease. The chronic phase lasts on average 2-3 years, in some cases – up to 10 years. This phase of chronic myeloid leukemia is characterized by an asymptomatic course or the gradual appearance of “mild” symptoms: weakness, some malaise, decreased ability to work and a feeling of fullness of the abdomen. An objective examination of a patient with chronic myeloid leukemia may reveal an enlargement of the spleen. According to blood tests, an increase in the number of granulocytes is detected up to 50-200 thousand / ml with an asymptomatic course of the disease and up to 200-1000 thousand / ml with “mild” signs.
In the initial stages of chronic myeloid leukemia, a slight decrease in hemoglobin levels is possible. Subsequently, normochromic normocytic anemia develops. When examining the blood smear of patients with chronic myeloid leukemia, there is a predominance of young forms of granulocytes: myelocytes, promyelocytes, myeloblasts. There are deviations from the normal level of granularity in one direction or another (abundant or very scarce). The cytoplasm of cells is immature, basophilic. Anisocytosis is determined. In the absence of treatment, the chronic phase passes into the acceleration phase.
The beginning of the acceleration phase can be indicated by both changes in laboratory parameters and a deterioration in the condition of patients. There may be an increase in weakness, an increase in the liver and a progressive enlargement of the spleen. In patients with this pathology, clinical signs of anemia and thrombocytopenia or trobocytosis are revealed: pallor, fatigue, dizziness, petechiae, hemorrhages, increased bleeding. Despite the ongoing treatment, the number of leukocytes in the blood of patients with chronic myeloid leukemia is gradually increasing. At the same time, there is an increase in the level of metamyelocytes and myelocytes, the appearance of single blast cells is possible.
Blast crisis is accompanied by a sharp deterioration of the patient’s condition with chronic myeloid leukemia. New chromosomal abnormalities arise, a monoclonal neoplasm transforms into a polyclonal one. There is an increase in cellular atypism with the suppression of normal hematopoietic sprouts. Pronounced anemia and thrombocytopenia are observed. The total number of blasts and promyelocytes in the peripheral blood is more than 30%, in the bone marrow – more than 50%. Patients with chronic myeloid leukemia lose weight and appetite. Extramedullary foci of immature cells (chloromas) arise. Bleeding and severe infectious complications develop.
The diagnosis is established on the basis of the clinical picture and the results of laboratory tests. The first suspicion of chronic myeloid leukemia often occurs when the level of granulocytes increases in a blood test prescribed as a preventive examination or examination in connection with another disease. To clarify the diagnosis, data from histological examination of the material obtained during sternal puncture of the bone marrow can be used, however, the final diagnosis of “chronic myeloid leukemia” is made when the Philadelphia chromosome is detected using PCR, fluorescent hybridization or cytogenetic examination.
The question of the possibility of making a diagnosis of chronic myeloid leukemia in the absence of the Philadelphia chromosome remains debatable. Many researchers believe that such cases can be explained by complex chromosomal disorders, which makes it difficult to identify this translocation. In some cases, the Philadelphia chromosome can be detected using reverse transcription PCR. With negative results of the study and an atypical course of the disease, it is usually not about chronic myeloid leukemia, but about undifferentiated myeloproliferative/myelodysplastic disorder.
Treatment tactics are determined depending on the phase of the disease and the severity of clinical manifestations. In the chronic phase, with an asymptomatic course and mild laboratory changes, they are limited to general strengthening measures. Patients with chronic myeloid leukemia are recommended to follow a work and rest regime, eat food rich in vitamins, etc. Treatment may include:
- Monochemotherapy. With an increase in the level of leukocytes, busulfan is used. After normalization of laboratory parameters and reduction of the spleen, patients with chronic myeloid leukemia are prescribed maintenance therapy or course treatment with busulfan. In blast crises, hydroxycarbamide is treated.
- Radiotherapy. Irradiation is usually used for leukocytosis in combination with splenomegaly. With a decrease in the level of leukocytes, they pause for at least a month, and then switch to supportive therapy with busulfan. Radiotherapy is also prescribed for chloromas.
- Polychemotherapy. In the progressive phase of chronic myeloid leukemia, it is possible to use one chemotherapy drug or polychemotherapy. Mitobronitol, hexaphosphamide or chlorethylaminouracil are used. As in the chronic phase, intensive therapy is carried out until the laboratory parameters are stabilized, and then they switch to maintenance doses. Courses of polyochemotherapy for chronic myeloid leukemia are repeated 3-4 times a year.
- Hemocorrection. If therapy is ineffective, leukocytapheresis is used. With severe thrombocytopenia, anemia, transfusions of thromboconcentrate and erythrocyte mass are performed.
- TCM. Bone marrow transplantation is performed in the first phase of chronic myeloid leukemia. Long-term remission can be achieved in 70% of patients.
- Removal of the spleen. If there are indications, splenectomy is performed. Emergency splenectomy is indicated for rupture or threat of rupture of the spleen, planned – for hemolytic crises, “wandering” spleen, recurrent perisplenitis and pronounced splenomegaly, accompanied by a violation of the functions of the abdominal organs.
The prognosis for chronic myeloid leukemia depends on many factors, the determining one of which is the time of initiation of treatment (in the chronic phase, activation phase or during a blast crisis). As unfavorable prognostic signs of chronic myeloid leukemia, a significant increase in the liver and spleen is considered (the liver protrudes from under the edge of the costal arch by 6 cm or more, the spleen by 15 cm or more), leukocytosis over 100×109 / l, thrombocytopenia less than 150×109 / l, thrombocytosis more than 500×109 / l, an increase in the level of blast cells in peripheral blood up to 1% or more, an increase in the total level of promyelocytes and blast cells in peripheral blood up to 30% or more.
The probability 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 this disease is 2.5 years, however, with timely initiation of therapy and a favorable course of the disease, this indicator can increase to several decades.