Treatment methods for myeloid leukemia and how the disease progresses. Myeloid leukemia - what is it? Chronic myeloid leukemia: causes, treatment, prognosis Chronic myeloid leukemia what


– a malignant myeloproliferative disease characterized by predominant damage to the granulocytic lineage. It may remain asymptomatic for a long time. It manifests itself as a tendency to low-grade fever, a feeling of fullness in the abdomen, frequent infections and an enlarged 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. The diagnosis is established taking into account the anamnesis, clinical picture and data laboratory research. Treatment – ​​chemotherapy, radiotherapy, transplant bone marrow.

General information

Chronic myeloid leukemia – cancer, resulting from a chromosomal mutation with damage to pluripotent stem cells and subsequent uncontrolled proliferation of mature granulocytes. Accounts for 15% of the total number of hemoblastoses in adults and 9% of total number leukemia in all age groups. Usually develops after 30 years, the peak incidence of chronic myeloid leukemia occurs at the age of 45-55 years. Children under 10 years of age are extremely rarely affected.

Chronic myeloid leukemia is equally common in women and men. Due to its asymptomatic or minimally symptomatic course, it may become an incidental finding during a blood test taken in connection with another disease or during preventive examination. In some patients, chronic myeloid leukemia is detected in the final stages, which limits treatment options and worsens survival rates. Treatment is carried out by specialists in the field of oncology and hematology.

Etiology and pathogenesis of chronic myeloid leukemia

Chronic myeloid leukemia is considered the first disease in which a connection between the development of pathology and a certain 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 sections of chromosomes 9 and 22. As a result of this replacement, a stable open reading frame is formed. Frame formation causes cell division to accelerate and inhibits 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 chronic myeloid leukemia are ionizing radiation and contact with certain chemical compounds. The result of the mutation is increased proliferation of pluripotent stem cells. In chronic myeloid leukemia, predominantly mature granulocytes proliferate, but the abnormal clone also includes other blood cells: erythrocytes, monocytes, megakaryocytes, and, less commonly, B- and T-lymphocytes. Normal hematopoietic cells do not disappear and, after suppression of the abnormal clone, can serve as the basis for normal proliferation of blood cells.

Chronic myeloid leukemia is characterized by a staged course. During the first, chronic (inactive) phase, there is a gradual worsening pathological changes while maintaining a satisfactory general condition. In the second phase of chronic myeloid leukemia - the acceleration phase, changes become obvious, progressive anemia and thrombocytopenia develop. The final stage 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 blast crisis phase, the condition of a patient with chronic myeloid leukemia sharply worsens and develops severe complications ending in the death of the patient. In some patients, the acceleration phase is absent; the chronic phase is immediately replaced by a blast crisis.

Symptoms of chronic myeloid leukemia

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 in the abdomen. An objective examination of a patient with chronic myeloid leukemia may reveal an enlarged spleen. Blood tests reveal an increase in the number of granulocytes to 50-200 thousand/μl in asymptomatic disease and up to 200-1000 thousand/μl 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 a blood smear of patients with chronic myeloid leukemia, a predominance of young forms of granulocytes is noted: myelocytes, promyelocytes, myeloblasts. There are deviations from the normal level of granularity in one direction or another (abundant or very scanty). The cytoplasm of the cells is immature, basophilic. Anisocytosis is detected. In the absence of treatment, the chronic phase passes into the acceleration phase.

The beginning of the acceleration phase of chronic myeloid leukemia can be indicated by both changes in laboratory parameters and deterioration of the patient’s condition. There may be increasing weakness, enlargement of the liver and progressive enlargement of the spleen. In patients with chronic myeloid leukemia, clinical signs of anemia and thrombocytopenia or trobocytosis are detected: pallor, fast fatiguability, dizziness, petechiae, hemorrhages, increased bleeding. Despite the treatment, the number of leukocytes in the blood of patients with chronic myeloid leukemia gradually increases. In this case, there is an increase in the level of metamyelocytes and myelocytes, and the appearance of single blast cells is possible.

The blast crisis is accompanied sharp deterioration condition of a patient with chronic myeloid leukemia. New chromosomal abnormalities arise, and the monoclonal neoplasm transforms into a polyclonal one. There is an increase in cellular atypia with inhibition of normal hematopoietic germs. Severe 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) appear. Bleeding and severe infectious complications.

Diagnosis of chronic myeloid leukemia

The diagnosis is made based on the clinical picture and laboratory results. The first suspicion of chronic myeloid leukemia often arises when the level of granulocytes in a general blood test, prescribed as a preventive examination or examination in connection with another disease, increases. Data can be used to clarify the diagnosis histological examination material obtained by sternal puncture of the bone marrow, however, the final diagnosis of “chronic myeloid leukemia” is made by identifying the Philadelphia chromosome using PCR, fluorescent hybridization or cytogenetic research.

The question of the possibility of making a diagnosis of chronic myeloid leukemia in the absence of the Philadelphia chromosome remains controversial. Many researchers believe that such cases can be explained by complex chromosomal abnormalities, which make identifying this translocation difficult. In some cases, the Philadelphia chromosome can be detected using reverse transcription PCR. If the test results are negative and the course of the disease is atypical, they usually speak not of chronic myeloid leukemia, but of undifferentiated myeloproliferative/myelodysplastic disorder.

Treatment of chronic myeloid leukemia

Treatment tactics are determined depending on the phase of the disease and severity clinical manifestations. In the chronic phase, with an asymptomatic course and mild laboratory changes, general strengthening measures are limited. Patients with chronic myeloid leukemia are advised to follow a work-rest schedule, eat foods rich in vitamins, etc. When the level of leukocytes increases, busulfan is used. After normalization of laboratory parameters and reduction of the spleen, patients with chronic myeloid leukemia are prescribed maintenance therapy or a course of treatment with busulfan. Radiotherapy is usually used for leukocytosis in combination with splenomegaly. When the level of leukocytes decreases, take a break for at least a month, and then switch to maintenance therapy with busulfan.

In the progressive phase of chronic myeloid leukemia, it is possible to use one chemotherapy drug or polychemotherapy. Mitobronitol, hexaphosphamide or chloroethylaminouracil are used. As in the chronic phase, intensive therapy is carried out until laboratory parameters stabilize, and then they switch to maintenance doses. Courses of polychemotherapy for chronic myeloid leukemia are repeated 3-4 times a year. For blast crises, treatment is carried out with hydroxycarbamide. If therapy is ineffective, leukocytapheresis is used. In cases of severe thrombocytopenia and anemia, transfusions of platelet concentrate and red blood cells are performed. For chloromas, radiotherapy is prescribed.

Bone marrow transplantation is performed in the first phase of chronic myeloid leukemia. Long-term remission can be achieved in 70% of patients. If indicated, 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 severe splenomegaly, accompanied by dysfunction of organs abdominal cavity.

Prognosis of chronic myeloid leukemia

The prognosis for chronic myeloid leukemia depends on many factors, the determining one of which is the moment of initiation of treatment (in the chronic phase, activation phase or during the blast crisis). Significant enlargement of the liver and spleen (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 100x10 9 /l, thrombocytopenia less than 150x10 9 /l are considered as unfavorable prognostic signs of chronic myeloid leukemia , thrombocytosis more than 500x10 9 /l, an increase in the level of blast cells in the peripheral blood to 1% or more, an increase in the total level of promyelocytes and blast cells in the peripheral blood to 30% or more.

The likelihood of an unfavorable outcome in chronic myeloid leukemia increases as the number of symptoms increases. The cause of death is infectious complications or severe hemorrhages. Average duration The lifespan of patients with chronic myeloid leukemia is 2.5 years, but with timely initiation of therapy and a favorable course of the disease, this figure can increase to several decades.

Definition. Chronic myeloid leukemia is a myeloproliferative disease with the formation of a tumor bone marrow clone of progenitor cells capable of differentiating into mature granulocytes, predominantly of the neutrophilic series.

ICD10: C92.1 – Chronic myeloid leukemia.

Etiology. The etiological factor of the disease may be infection with a latent virus. The triggering factor that reveals the antigens of the latent virus can be ionizing radiation and toxic effects. A chromosomal aberration appears - the so-called Philadelphia chromosome. It is the result of a reciprocal translocation of part of the long arm of chromosome 22 to chromosome 9. On chromosome 9 there is the abl proto-oncogene, and on chromosome 22 the c-sis proto-oncogene, which is a cellular homologue of the simian sarcoma virus (transforming gene virus), as well as the bcr gene. The Philadelphia chromosome appears in all blood cells with the exception of macrophages and T-lymphocytes.

Pathogenesis. As a result of the influence of etiological and triggering factors, a tumor clone appears in the bone marrow from a progenitor cell, capable of differentiating into mature neutrophils. The tumor clone spreads in the bone marrow, displacing normal hematopoietic germs.

A huge number of neutrophils appears in the blood, comparable to the number of red blood cells - leukemia. One of the causes of hyperleukocytosis is the switching off of the bcr and abl genes related to the Philadelphia chromosome, which causes a delay in the final completion of neutrophil development with the expression of apoptosis (natural death) antigens on their membrane. Fixed spleen macrophages must recognize these antigens and remove old, expired cells from the blood.

The spleen cannot cope with the rate of destruction of neutrophils from the tumor clone, as a result of which compensatory splenomegaly is initially formed.

Due to metastasis, foci of tumor hematopoiesis appear in the skin, other tissues and organs. Leukemic infiltration of the spleen contributes to its even greater enlargement. In the huge spleen, normal red blood cells, white blood cells, and platelets are intensively destroyed. This is one of the leading causes of hemolytic anemia and thrombocytopenic purpura.

During its development and metastasis, a myeloproliferative tumor undergoes mutations and turns from monoclonal to multiclonal. This is evidenced by the appearance in the blood of cells with karyotype aberrations other than the Philadelphia chromosome. As a result, an uncontrolled tumor clone of blast cells is formed. Acute leukemia occurs. Leukemic infiltration of the heart, lungs, liver, kidneys, progressive anemia, thrombocytopenia turn out to be incompatible with life, and the patient dies.

Clinical picture. Chronic myeloid leukemia goes through 3 stages in its clinical development: initial, advanced benign (monoclonal) and terminal malignant (polyclonal).

initial stage corresponds to myeloid hyperplasia of the bone marrow in combination with minor changes in peripheral blood without signs of intoxication. The disease at this stage does not manifest any clinical symptoms and often goes unnoticed. Only in isolated cases can patients feel dull, aching pain in the bones, and sometimes in the left hypochondrium. Chronic myeloid leukemia at the initial stage can be recognized by the random detection of “asymptomatic” leukocytosis, followed by sternal puncture.

An objective examination at the initial stage may reveal a slight enlargement of the spleen.

Expanded stage corresponds to a period of monoclonal tumor proliferation with moderate metastasis (leukemic infiltration) outside the bone marrow. It is characterized by patient complaints of progressive general weakness and sweating. Body weight is lost. There is a tendency to lingering colds. They are worried about pain in the bones, in the left side in the area of ​​the spleen, the enlargement of which the patients themselves notice. In some cases, a prolonged low-grade fever is possible.

An objective examination reveals severe splenomegaly. The organ can occupy up to half the volume of the abdominal cavity. The spleen is dense, painless, and with extremely severe splenomegaly it is sensitive. With a splenic infarction, intense pain suddenly appears in the left half of the abdomen, a friction sound of the peritoneum above the infarction area, and body temperature rises.

When pressing with your hand on the sternum, the patient may experience sharp pain.

In most cases, moderate hepatomegaly is detected, caused by leukemic infiltration of the organ.

Symptoms of damage to other organs may appear: gastric and duodenal ulcers, myocardial dystrophy, pleurisy, pneumonia, leukemic infiltration and/or hemorrhages in the retina, menstrual irregularities in women.

Overeducation uric acid with the breakdown of neutrophil nuclei, it often leads to the formation of urate stones in the urinary tract.

Terminal stage corresponds to the period of polyclonal hyperplasia of the bone marrow with multiple metastasis of various tumor clones to other organs and tissues. It is divided into the phase of myeloproliferative acceleration and blast crisis.

Phase myeloproliferative acceleration can be characterized as a pronounced exacerbation of chronic myeloid leukemia. All subjective and objective symptoms of the disease worsen. I am constantly experiencing severe pain in the bones, joints, and spine.

Due to leukemoid infiltration, severe damage to the heart, lungs, liver, and kidneys occurs.

An enlarged spleen can occupy up to 2/3 of the abdominal cavity. Leukemids appear on the skin - pink or brown spots, slightly raised above the surface of the skin, dense, painless. These are tumor infiltrates consisting of blast cells and mature granulocytes.

Enlarged lymph nodes are detected, in which solid tumors such as sarcomas develop. Foci of sarcomatous growth can occur not only in the lymph nodes but also in any other organ, bones, which is accompanied by corresponding clinical symptoms.

There is a tendency to subcutaneous hemorrhages - thrombocytopenic purpura. Signs of hemolytic anemia appear.

Due to a sharp increase in the content of leukocytes in the blood, often exceeding the level of 1000 * 10 9 / l (true “leukemia”), a clinical syndrome of hyperleukocytosis with shortness of breath, cyanosis, damage to the central nervous system, manifested by mental disorders, visual impairment as a result of edema can form optic nerve.

Blast crisis is a sharp exacerbation of chronic myeloid leukemia and, according to clinical and laboratory data, represents acute leukemia.

The patients are in serious condition, exhausted, and have difficulty turning in bed. They are worried about severe pain in the bones and spine, debilitating fever, and heavy sweats. The skin is pale bluish with multi-colored bruises (thrombocytopenic purpura), pink or brown lesions of leukemia. The icterus of the sclera may be noticeable. Sweet's syndrome may develop: acute neutrophilic dermatosis with high fever. Dermatosis is characterized by painful lumps, sometimes large nodules, on the skin of the face, arms, and torso.

Peripheral lymph nodes are enlarged and stony in density. The spleen and liver are enlarged to the maximum possible size.

As a result of leukemic infiltration, severe damage to the heart, kidneys, and lungs occurs with symptoms of cardiac, renal, and pulmonary failure, which leads to the patient’s death.

Diagnostics.

In the initial stage of the disease:

    Complete blood count: the number of red blood cells and hemoglobin is normal or slightly reduced. Leukocytosis up to 15-30*10 9 /l with a shift of the leukocyte formula to the left to myelocytes and promyelocytes. Basophilia, eosinophilia, and moderate thrombocytosis are noted.

    Biochemical blood test: increased level uric acid.

    Sternal punctate: increased content of cells of the granulocytic line with a predominance of young forms. The number of blasts does not exceed upper limit norms. The number of megakaryocytes is increased.

In the advanced stage of the disease:

    General blood test: the content of red blood cells and hemoglobin is moderately reduced, the color indicator is about one. Reticulocytes and single erythrokaryocytes are detected. Leukocytosis from 30 to 300*10 9 /l and above. A sharp shift in the leukocyte formula to the left to myelocytes and myeloblasts. The number of eosinophils and basophils is increased (eosinophil-basophil association). The absolute content of lymphocytes is reduced. Thrombocytosis, reaching 600-1000*10 9 /l.

    Histochemical examination of leukocytes: the content of alkaline phosphatase in neutrophils is sharply reduced.

    Biochemical blood test: increased levels of uric acid, calcium, decreased cholesterol, increased LDH activity. Bilirubin levels may increase due to hemolysis of red blood cells in the spleen.

    Sternal punctate: brain with a large content of cells. The number of cells of granulocytic lineages is significantly increased. Blasts no more than 10%. Many megakaryocytes. The number of erythrokaryocytes is moderately reduced.

    Cytogenetic analysis: the Philadelphia chromosome is detected in myeloid cells of the blood, bone marrow, and spleen. This marker is absent in T lymphocytes and macrophages.

In the terminal stage of the disease in the phase of myeloproliferative acceleration:

    Complete blood count: significant decrease in hemoglobin and red blood cells in combination with anisochromia, anisocytosis, poikilocytosis. Single reticulocytes may be detected. Neutrophilic leukocytosis, reaching 500-1000*10 9 /l. A sharp shift in the leukocyte formula to the left to blasts. The number of blasts can reach 15%, but there is no leukemic failure. The content of basophils (up to 20%) and eosinophils is sharply increased. Reduced platelet count. Functionally defective megathrombocytes and fragments of megakaryocyte nuclei are identified.

    Sternal punctate: the erythrocyte germ is suppressed more significantly than in the advanced stage, the content of myeloblastic cells, eosinophils and basophils is increased. Reduced number of megakaryocytes.

    Cytogenetic analysis: a specific marker of chronic myeloid leukemia is detected in myeloid cells - the Philadelphia chromosome. Other chromosomal aberrations appear, which indicates the emergence of new clones of tumor cells.

    The results of a histochemical study of granulocytes and biochemical blood parameters are the same as in the advanced stage of the disease.

In the terminal stage of the disease in the blast crisis phase:

    General blood test: a deep drop in the content of red blood cells and hemoglobin with a complete absence of reticulocytes. Slight leukocytosis or leukopenia. Neutropenia. Sometimes basophilia. Lots of blasts (over 30%). Leukemic failure: the smear contains mature neutrophils and blasts, and there are no intermediate maturing forms. Thrombocytopenia.

    Sternal punctate: the number of mature granulocytes, cells of the erythrocyte and megakaryocytic lines is reduced. The number of blast cells is increased, including abnormal ones with enlarged, deformed nuclei.

    In histological preparations of skin leukemia, blast cells are detected.

Generalized criteria for clinical and laboratory diagnosis of chronic myeloid leukemia:

    Neutrophilic leukocytosis in peripheral blood over 20*10 9 /l.

    The presence in the leukocyte formula of proliferating (myelocytes, promyelocytes) and maturing (myelocytes, metamyelocytes) granulocytes.

    Eosinophilic-basophilic association.

    Myeloid hyperplasia of the bone marrow.

    Decreased neutrophil alkaline phosphatase activity.

    Detection of the Philadelphia chromosome in blood cells.

    Splenomegaly.

Clinical and laboratory criteria for assessing risk groups necessary to select the optimal treatment tactics for advanced stage chronic myeloid leukemia.

    In peripheral blood: leukocytosis over 200*10 9 /l, blasts less than 3%, the sum of blasts and promyelocytes more than 20%, basophils more than 10%.

    Thrombocytosis is more than 500*10 9 /l or thrombocytopenia is less than 100*10 9 /l.

    Hemoglobin is less than 90 g/l.

    Splenomegaly - lower pole of the spleen 10 cm below the left costal arch.

    Hepatomegaly is the anterior edge of the liver below the right costal arch by 5 cm or more.

Low risk – the presence of one of the signs. Intermediate risk – 2-3 signs. High risk – 4-5 signs.

Differential diagnosis. It is carried out with leukemoid reactions, acute leukemia. The fundamental difference between chronic myeloid leukemia and similar diseases is the detection of the Philadelphia chromosome in blood cells, a reduced level of alkaline phosphatase in neutrophils, and an eosinophilic-basophilic association.

Survey plan.

    General blood analysis.

    Histochemical study of the content of alkaline phosphatase in neutrophils.

    Cytogenetic analysis of blood cell karyotype.

    Biochemical blood test: uric acid, cholesterol, calcium, LDH, bilirubin.

    Sternal puncture and/or trepanobiopsy of the iliac wing.

Treatment. When treating patients with chronic myeloid leukemia, the following methods are used:

    Therapy with cytostatics.

    Administration of alpha-2 interferon.

    Cytopheresis.

    Radiation therapy.

    Splenectomy.

    Bone marrow transplantation.

Therapy with cytostatics begins at the advanced stage of the disease. At low and medium risk, monotherapy with one cytostatic agent is used. At high risk and in the terminal stage of the disease, polychemotherapy with several cytostatics is prescribed.

The drug of first choice in the treatment of chronic myeloid leukemia is hydroxyurea, which has the ability to suppress mitosis in leukemia cells. Start with 20-30 mg/kg/day per os at a time. The dose is adjusted weekly depending on changes in the blood picture.

If there is no effect, use myelosan 2-4 mg per day. If the level of leukocytes in the peripheral blood is reduced by half, the dose of the drug is also halved. When leukocytosis drops to 20*10^9/l myelosan is temporarily discontinued. Then they switch to a maintenance dose - 2 mg 1-2 times a week.

In addition to myelosan, you can use myelobromol at 0.125-0.25 once a day for 3 weeks, then maintenance treatment at 0.125-0.25 once every 5-7-10 days.

Polychemotherapy can be carried out according to the ABAMP program, which includes the administration of cytosar, methotrexate, vincristine, 6-mercaptopurine, prednisolone. There are other schemes of multicomponent therapy with cytostatics.

The use of alpha interferon (reaferon, intron A) is justified by its ability to stimulate antitumor and antiviral immunity. Although the drug does not have a cytostatic effect, it still promotes leukopenia and thrombocytopenia. Alpha interferon is prescribed in the form of subcutaneous injections of 3-4 million units/m 2 2 times a week for six months.

Cytopheresis allows you to reduce the content of leukocytes in peripheral blood. A direct indication for the use of this method is resistance to chemotherapy. Patients with hyperleukocytosis and hyperthrombocytosis syndrome with predominant damage to the brain and retina need urgent cytopheresis. Cytopheresis sessions are carried out from 4-5 times a week to 4-5 times a month.

Indication for local radiation therapy is giant splenomegaly with perisplenitis, tumor-like leukemias. The dose of gamma radiation to the spleen is about 1 Gray.

Splenectomy is used for threatening rupture of the spleen, deep thrombocytopenia, and severe hemolysis of red blood cells.

Bone marrow transplantation gives good results. In 60% of patients undergoing this procedure, complete remission is achieved.

Forecast. The average life expectancy of patients with chronic myeloid leukemia in its natural course without treatment is 2-3.5 years. The use of cytostatics increases life expectancy to 3.8-4.5 years. A more significant extension of the life expectancy of patients is possible after bone marrow transplantation.

Chronic myeloid leukemia (CML)- myeloproliferative chronic illness, in which there is an increased formation of granulocytes (mainly neutrophils, as well as promyelocytes, myelocytes, metamyelocytes), which are the substrate of the tumor. In most cases, the natural outcome of the disease is a blast crisis, characterized by the appearance of a large number of blast cells, refractoriness to therapy and ending in death.

Etiology and pathogenesis. The cause of pathological cell growth is considered to be a mutation in the myelopoiesis precursor cell (a partially determined pluripotent cell). This is proven by the discovery of a specific marker in patients with CML - a pathological Ph chromosome (Philadelphia) in the cells of myeloid, erythroid, monocyte and platelet lineages. The Ph chromosome is a common cellular marker that confirms the origin of the entire pathological clone of cells in CML from one mother. Despite the fact that all three bone marrow sprouts are leukemic, in the advanced stage of CML there is unlimited growth, as a rule, of one sprout - the granulocytic sprout. The production of megakaryocytes in the bone marrow and platelets in the peripheral blood increases significantly.

As the disease progresses, the monoclonal stage is replaced by a polyclonal stage, which is proven by the appearance of cells with a different incorrect set of chromosomes. This reveals the law of tumor progression to which this leukemia obeys.

CML is more common in adults aged 30-70 years; There is a slight predominance of men. CML is the most common of all leukemias, accounting for 20% of hemoblastoses in adults.

Classification. As noted, the disease naturally goes through two stages of development - monoclonal and polyclonal. This is consistent with three stages of chronic myeloid leukemia in clinical presentation.

Stage I - initial- myeloid proliferation of bone marrow
ha + minor changes in the blood without symptoms of intoxication (in the periphery
ric blood there are up to 1-3% blasts). ^e

Stage II - expanded- pronounced clinical and hematological manifestations (intoxication with decay products of leukemic cells, increased


e liver and spleen, myeloid proliferation of bone marrow + changes in the blood). In the peripheral blood there are up to 10% blasts. 116 Stage III - terminal(corresponds to the development of a polyclonal tumor) - refractoriness to ongoing cytostatic therapy, wasting, significant enlargement of the spleen and liver, dystrophic changes in internal organs, pronounced changes in the blood (anemia, lombopenia). For terminal stage CML is characterized by development


I, called blast crisis, is the appearance of neoplasm cells in the peripheral blood (up to 30-90%), and therefore the disease takes on the characteristics of acute leukemia. Most often, in the bone marrow and peripheral blood, ovarian cancer is characterized by the appearance of myeloblasts, but undifferentiated blast cells can also be found. Karyological examination reveals the polyclonal nature of pathological cells. At the same time, significant inhibition of thrombocytopoiesis occurs, and hemorrhagic syndrome develops. There is also a lymphoblastic variant of blast crisis (a large number of lymphoblasts appear in the bone marrow and peripheral blood).

Clinical picture. Clinical manifestations of CML can be expressed in large syndromes.

Myeloproliferative syndrome, which is based on myeloid proliferation of the bone marrow, includes:

a) general symptoms caused by intoxication, growths of leukemia
ny cells in the bone marrow, spleen and liver (sweating, weakness,
loss of body weight, heaviness and pain in the spleen and liver), especially
salgia;

b) enlargement of the liver and spleen;

c) leukemic infiltrates in the skin;

d) characteristic changes in the bone marrow and peripheral blood.
Syndrome caused by complications:

a) hemorrhagic diathesis (hemorrhages and thrombosis due to abnormal
of procoagulant and platelet components of hemostasis);

b) purulent-inflammatory (pneumonia, pleurisy, bronchitis, purulent
lesions of the skin and subcutaneous fat) caused by a sharp
decreased immune activity;

c) uric acid diathesis (hyperuricemia due to increased breakdown
granulocytes).

Different severity of syndromes on different stages The disease causes a fairly polymorphic clinical picture. You can observe patients who do not show any complaints and are fully able to work, and patients with severe damage to internal organs, exhausted, completely incapacitated.

At stage I of the diagnostic search in the initial stage of the disease, patients may not make complaints, and the disease will be diagnosed at subsequent stages. General complaints (weakness, sweating, weight loss) can occur at the most various diseases, therefore, they cannot be considered at stage I as specific for CML. Only later, when other symptoms indicating CML are identified, can they be interpreted as an expression of myeloproliferative syn-

1severity and pain in the left and right hypochondrium are usually explained by an enlargement of the spleen and liver. In combination with complaints of general Pj* KTe pa and pain in the bones, they can direct the doctor to a myeloid fermentative disease.


In the terminal stage of the disease, some of the complaints may be due to
the occurrence of complications: purulent-inflammatory, hemorrhagic
diathesis, uric acid diathesis. g °

At stage I, you can obtain information about changes in the hemogram and previous treatment (cytostatic drugs). Consequently, “if a patient who has already been diagnosed with CML comes into the doctor’s field of vision, the subsequent diagnostic search is greatly simplified. It is important to find out from patients information about the treatment carried out and the ineffectiveness of the drugs, before at this moment improving general state decreased the number of leukocytes. Such information will allow us to assume a transition to the polyclonal (terminal) stage of the disease.

At the second stage of the diagnostic search, it is possible to obtain information that allows us to make an assumption: 1) about the nature of the pathological process, i.e. the essence of the disease itself; 2) about the stage of the disease; 3) about possible complications.

In the advanced and terminal stages, signs are revealed that significantly confirm the assumption of CML: pallor skin(due to increasing anemia), skin hemorrhages and infiltrates (more typical for the terminal stage of CML). An essential symptom is splenomegaly (without enlargement of the lymph nodes), combined with an enlarged liver, which, with appropriate complaints and medical history, can be regarded as a manifestation of myeloproliferative syndrome.

With the development of complications, for example, splenic infarction, there is sharp pain on palpation and friction noise of the peritoneum over the spleen. Gradually, the spleen becomes dense (its mass is 6-9 kg, descends with the lower pole into the pelvis).

The most important data for the diagnosis of CML are obtained at stage III of the diagnostic search.

In stage I of the disease, leukocytosis is detected in the peripheral blood (more than 50 10 9 /l with neutrophilia (granulocytes of all stages of maturation - myelocytes, young, stab), eosinophilic-basophilic association. The number of platelets is not changed (sometimes slightly increased). Sometimes detected a small number of blasts - up to 1-3%. The bone marrow is rich in cellular elements with a predominance of granulocytic elements. The number of eosinophils, basophils, granulocytes can be increased.

In stage II, the number of leukocytes is 50-500 10 9 /l, the content of immature forms is increased (promyelocytes make up 20-30%), blasts make up up to 10%, platelets are reduced or increased. In the bone marrow, pronounced multicellularity is noted, in the leukogram there is a sharp shift to the left, the content of promyelocytes and blasts is increased - about 10%

In stage III, the number of leukocytes is small (up to 50 10 9 / l), there are many immature forms, blasts make up more than 10%, among them there are ugly forms. The platelet count is reduced. In the bone marrow, the content of blasts is increased, erythropoiesis and thrombocytopoiesis are suppressed.

Functional properties of leukocytes and the content of enzymes in them
changed: decreased activity of neutrophil alkaline phosphatase, on R in
shen ability for phagocytosis. During puncture of an enlarged spleen
advanced stage of the disease, a predominance of myeloid is detected
cells (which normally never occurs). y.

This stage turns out to be decisive in identifying blast P _ for: an increase in the number of blast cells in the bone marrow and periphery


0 blood (the total number of blasts and promyelocytes is 20% c1C, while outside the blast crisis this amount usually does not exceed 10-15%) -

Bone sintigraphy helps to detect an increase in the bridgehead of hematopoiesis (the study is performed when the diagnosis is unclear; it is not mandatory for all patients with CML).

Diagnostics. Detection of CML in the advanced stage of the disease does not present any difficulties and is based on characteristic data from a blood test, the results of bone marrow examination, and enlargement of the liver and spleen. ^ The diagnostic criteria for the disease are: . leukocytosis more than 20-10 9 /l;

The appearance of proliferating forms in the leukocyte formula (mye-
loblasts and promyelocytes) and maturing granulocytes (myelocytes, me-

tamyelocytes);

Myeloid proliferation of bone marrow (according to myelogram

and trepanobiopsy);

Decreased neutrophil alkaline phosphatase activity (less than

Detection of the Ph chromosome in hematopoietic cells;

Expansion of the “bridgehead” of hematopoiesis (according to scintigraphy

Increased size of the spleen and liver.
Differential diagnosis. CML should be differentiated from

called leukemoid reactions, which can occur in a number of diseases (tuberculosis, cancer, various infections, kidney failure, etc.). According to the definition of A.I. Vorobyov, leukemoid reaction is “changes in the blood and hematopoietic organs, reminiscent of leukemia and other tumors of the hematopoietic system, but not transforming into the tumor they resemble.” With the leukemoid reaction, high leukocytosis is observed, immature neutrophils appear in the peripheral blood, but the basophilic-eosinophilic association is not detected. Differential diagnosis is based on identifying the underlying disease (cancer, tuberculosis, etc.), as well as on increasing the activity of neutrophil alkaline phosphatase (instead of reducing it in CML). During sternal puncture, the leukemoid reaction is characterized by an increase in the content of myelocytes, but the Ph chromosome is never detected.

Treatment. The main goal of treating any hemoblastosis (including CML) is to eliminate or suppress the growth of the pathological cell clone. However, in relation to chronic leukemia, this does not mean that any patient who has a blood system disease immediately needs to be actively treated with cytostatic drugs that suppress tumor growth.

In the initial stage of the disease (in good health, but not
changes in peripheral blood and bone marrow) are necessary
we provide general restorative therapy, proper nutrition, adherence to the regime

Ore and rest (it is very important to avoid sun exposure). The patient must be under the supervision of a physician; Periodically (once every 3-6 months) it is necessary to examine peripheral blood.

If symptoms of disease progression appear, it is necessary
Carry out cytostatic therapy, and the volume of such treatment depends on
it depends on the stage of the disease. When clear symptoms of a tumor appear,
growth (increase in the size of the spleen, liver, as well as an increase in


the number of leukocytes compared to the previous period, both) carry out the so-called primary restraining therapy. Conventional treatment begins when the leukocyte count is 50-70-10 9 /l. Ambulatop ° use hydroxyurea (hydrea) in low doses (with mandatory hematological monitoring); after achieving clinical and/or hematological remission, the issue of maintenance therapy is decided

In the advanced stage of the disease, the amount of chemotherapy depends on the “risk group”, determined by the presence of unfavorable signs - ° T

1) leukocytosis more than 20010 9 /l, blasts more than 3%, the sum of blasts and pp 0 myelocytes in the blood more than 20 %, the number of basophils in the blood is more than 10 %"■

2) decrease in hemoglobin to a level of less than 90 g/l;

3) thrombocytosis more than 500 10 9 /l or thrombocytopenia less than 100 10 9 /l -

4) splenomegaly (the spleen is palpated 10 cm below the costal arch or more);

5) hepatomegaly (the liver is palpated 5 cm below the costal arch And more).

Low risk - presence of one sign; intermediate risk - the presence of 2-3 signs; high risk - the presence of 4 signs or more. At low and intermediate risk, monochemotherapy is initially indicated; at high risk, polychemotherapy is recommended from the very beginning.

In the advanced stage, a course of chemotherapy is carried out. Hydrea is used, but in large doses(daily 2-3 doses) under hematological control: when the number of leukocytes and platelets decreases, the dose of the drug is reduced, and when the leukocyte count is 10-20 10 9 / l and platelets 100-10 9 / l, the drug is discontinued. If earlier effective drugs do not have an effect within 3-4 weeks, then a course of treatment with another cytostatic should be carried out. So, if hydrea turns out to be ineffective, then myelosan (busulfan, mileran), myelobromol are prescribed.

After a course of chemotherapy, maintenance therapy is carried out according to a scheme close to the scheme of primary restraining therapy. Drugs that have had a therapeutic effect during a course of chemotherapy are used.

Polychemotherapy is carried out in courses with high degree risk, as well as in the terminal stage of CML; in blast crisis - in a volume corresponding to therapy for acute illness. They use drugs that have a cytostatic effect on proliferating elements (cytosar, methotrexate, vincristine, antitumor antibiotic rubomycin hydrochloride). Polychemotherapy courses are short (5-14 days with breaks of 7-10 days).

Currently, fundamentally new methods of treatment have appeared
tion of CML - cytokine α-interferon (α-IFN). The point is that in the process
myeloid proliferation megakaryocytes and platelets secrete pain
a large number of growth factors that themselves contribute to
further proliferation of mutant pluripotent and oligopotent
stem cells, and in addition, stromal cells. All this leads
further progression of the disease, as well as the development of fibrous and
changes in the bone marrow. Meanwhile, it has been proven that α-IFN, in its chi
chemical structure and functional properties is an antagonist
growth factors; it releases substances that inhibit the stimulus
destructive effect of megakaryocytes on hematopoiesis and have antipro-
ferative activity in relation to the parent cells of the blood ^
 creations; in addition, α-IFN stimulates the antitumor immune system ^
 Consequently, conditions are created to maintain normal blood


ia, while α-IFN does not have a cytostatic effect, which is a very attractive property, since there is no depressive effect on normal bone marrow cells. In practice, recombinant α-IFN - reaferon, or

tpon "A", which is administered intramuscularly or subcutaneously in doses of 2 to 9 MI/m2 per day (according to different authors) for 2-6 months /f MI = 1 ° 00 °°0 E D)" allowing achieve hematological remission

and v many patients. When treated with this drug, a “type-like” syndrome may appear - fever, headache, "swelling in the muscles, general bad feeling However, taking paracetamol reduces these phenomena.

Intron “A” is sometimes combined with a cytostatic drug - hydrea or cytosine arabinoside (cytosar), which improves treatment results; The 5-year survival rate when treated with intron “A” is 32-89 months (in 50% of patients), while when treated with myelosan this figure is 44-48 months.

It is very significant that during the treatment of α-IFN, not only hematological, but also cytogenetic remission can occur, when the Ph chromosome is not detected at all in the blood and bone marrow cells, which allows us to speak not so much about remission, but about complete recovery from

Currently, the main “event” in the treatment of CML is a new drug - a mutant tyrosine kinase blocker (p210 protein) - Gleevec (STI-571). The drug is prescribed at a dose of 400 mg/m2 for 28 days. For blast crisis of CML, the dose is 600 mg/(m 2 -day). The use of the drug leads to complete remission of the disease without eradication of the tumor clone. Currently, Gleevec is the drug of choice for CML.

If the spleen is significantly enlarged, irradiation is sometimes performed. x-rays, which leads to a decrease in its size.

For purulent-inflammatory complications, antibiotic therapy is performed.

Blood transfusions for CML are indicated in cases of severe anemic syndrome that is not amenable to cytostatic therapy, or treatment with iron supplements in cases of iron deficiency. Patients with CML are registered at a dispensary and undergo periodic examinations with mandatory hematological monitoring.

Forecast. The life expectancy of patients with CML is on average 3-5 years, in some patients it reaches 7-8 years. Life expectancy after blast crisis rarely exceeds 12 months. The use of Intran A significantly changes the prognosis of the disease for the better.

Prevention. There are no measures to prevent CML, and therefore we can only talk about secondary prevention disease, which consists of preventing exacerbations of the disease (maintenance therapy, exclusion of insolation, colds, etc.).

Hematologist

Higher education:

Hematologist

Samara State medical University(SamSMU, KMI)

Level of education - Specialist
1993-1999

Additional education:

"Hematology"

Russian Medical Academy Postgraduate Education


Often, chromosomal malfunctions manifest themselves in the most unexpected disorders. One of these manifestations is chronic myeloid leukemia, a tumor lesion of the blood. In the vast majority of cases, the process of hematopoiesis occurring in the red bone marrow undergoes changes due to chromosome damage. The most favorable prognosis is provided by a bone marrow transplant. Usually a donor is selected from among relatives.

The essence of pathology

Chronic myeloid leukemia (CML) is characterized by an increase in the blood levels of granulocytes, a type of white blood cell. Forming uncontrollably in the bone marrow, a significant part of them enters the blood immature. The concentration of other types of leukocytes decreases, and young, altered cells can reach maturity.

At the beginning of the development of pathology, the number of leukocytes is about 20,000/μl. As it progresses, this figure changes to 400,000/µl. Cells are found in the blood varying degrees maturity - immature (promyelocytes, myelocytes, metamyelocytes) and mature (band neutrophils).

Abnormalities in chromosomes are recorded. Most often, the disease provokes a noticeable increase in the concentration of other types of leukocytes (basophils and eosinophils). This is evidence of a severe form of CML. In patients, the spleen increases in size, and the number of myeloblasts (progenitors of granulocytes) increases in the bone marrow and blood.

Causes of the disease

Certain genes control cell growth and division. Some stimulate the development process (oncogenes), others slow it down, causing physiological cell death (suppressors). Myeloid leukemia is caused by DNA mutations that promote the spread of oncogenes or “turn off” suppressors.

In cells human body contains 23 pairs of chromosomes. Typically, CML begins to develop when fragments are “exchanged” between chromosomes 9 and 22 (translocation). An abnormal gene is formed, and chromosome 22 decreases in size. A transformed chromosome, called the Philadelphia chromosome, is observed in the altered cells of almost all patients diagnosed with chronic myeloid leukemia. It is this that causes the growth and chaotic division of pathological cells.

In a small number of patients, the harmful cells do not contain the altered chromosome. It is believed that the affected gene is formed differently in them. It is extremely rare that patients do not have either an altered gene or a “broken” chromosome. It is assumed that in this case the development is provoked by unknown oncogenes.

Experts do not classify a chromosome defect as genetic, but studies have shown that there is a high probability of developing the pathology in children whose parents have some kind of genetic abnormality (Down syndrome). The occurrence of chronic myeloid leukemia is influenced by certain external factors:

  • high doses of radiation exposure;
  • negative impact chemical substances(alcohols, epoxy resins, alkenes, ketones, aldehydes);
  • age (over 30 years);
  • gender (more often the disease is diagnosed in men).

A weakened immune system may be a risk factor. Smoking contributes to a more severe course of the disease.

Classification of chronic myeloid leukemia

There are several classifications of pathology. According to the general taxonomy, there are several types of chronic myeloid leukemia:

  • with the Philadelphia chromosome in adults;
  • with the Philadelphia chromosome in patients over 60 years of age;
  • atypical (without the Philadelphia chromosome);
  • in children (infantile form without the Philadelphia chromosome, juvenile form, little different from CML with a transformed chromosome in adults).

By clinical picture pathology can be:

  • benign;
  • progressive;
  • splenic;
  • abdominal;
  • tumor;
  • bone marrow

There are three degrees of severity of the disease:

  1. Chronic – blast level less than 15%;
  2. Acceleration (acceleration) – the number of blasts is 15-29%. Blasts and promyelocytes in the blood and bone marrow account for more than 30%, thrombocytopenia develops ( low content platelets) not responding to therapy;
  3. Blast crisis - more than 30% blasts, areas of extramedullary hematopoiesis (outside the bone marrow) appear.

There is also recurrent chronic myeloid leukemia - an increase in the number of blasts after remission.

Symptoms of chronic myeloid leukemia

Often the pathology is initially asymptomatic. Nonspecific signs gradually appear:

  • weakness;
  • weight loss;
  • hyperthermia;
  • night sweats;
  • flatulence.

In the future, you may experience:

  • increase in the size of the spleen;
  • pallor;
  • bleeding;
  • noticeable enlargement of lymph nodes;
  • skin rashes.

With an increase in the size of the spleen, the patient may feel pain or a feeling of heaviness in the left side of the abdomen. With acceleration, the severity of symptoms increases. The last stage of chronic myeloid leukemia, in addition to the already manifested symptoms, is characterized by:

  • hemorrhages;
  • rapid drop in body weight;
  • heavy sweats;
  • prolonged joint and bone pain;
  • fever with severe chills.

The benign course of the pathology lasts several years, the malignant course - from three to six months. Often with chronic myeloid leukemia, infectious diseases develop and signs of intoxication appear. Periods of exacerbation are followed by remissions.

Diagnosis of chronic myeloid leukemia

During a physical examination, the doctor, having studied the patient’s medical history, assesses the condition of the liver, spleen, and lymph nodes. Subsequent diagnosis may include:

  • blood tests (fixing quantitative and qualitative blood parameters);
  • bone marrow puncture - biopsy or aspiration (determining the presence of affected cells);
  • examination of selected samples of blood, bone marrow, bones, cerebrospinal fluid, lymph node tissue (detection of the type of leukemia and assessment of the presence of leukemia cells);
  • analysis to detect chromosomal abnormalities;
  • radiography chest(detection of pulmonary pathologies);
  • Ultrasound, CT, MRI (visualization of tissues, organs).

In about a quarter of patients, chronic myeloid leukemia is discovered by chance during a medical examination. In some patients, macrophages are detected in the bone marrow. The concentration of megakaryocytes is increased. Electron microscopy at each stage of their maturation, it reveals a lag in the development of the nucleus from the cytoplasm. Infiltration is detected in the red pulp of the spleen.

The concentration of uric acid and vitamin B12 increases in the blood serum. Sometimes high content uric acid causes the formation of urates in bladder and the development of gouty arthritis. Sometimes the spleen reaches such a size that it descends into the pelvic area. With significant splenomegaly, the liver often increases in size. The final confirmation of the diagnosis is registration of the transformed chromosome. In other pathologies, the presence of this marker in the blood and bone marrow is not noted.

Pathology therapy

Therapy for chronic myeloid leukemia is determined by the stage of the pathology. At an early stage, restorative treatment, a balanced diet enriched with vitamins, and regular medical check-ups are recommended. In other cases, CML is treated with medications that help reduce the size of the spleen and reduce the activity of malignant cells. The patient’s life expectancy directly depends on the adequacy and timeliness of the therapy. Therapy is carried out using several methods:

  1. Drug treatment (Cytosar, Alpha interferon, Myelosan);
  2. Bone marrow transplantation (the likelihood of recovery is higher during surgery in the early stages of the pathology; preferred donors are the patient’s relatives);
  3. Radiation therapy (the goal is to destroy malignant cells and reduce the rate of their development);
  4. Removal of the spleen (usually at the last stage of pathology). Indications for surgical intervention thrombocytopenia, the threat of damage to the spleen, and obvious discomfort caused by the size of the organ may occur.

If taking medications does not give the expected effect, leukophoresis is used - cellular cleansing of the blood from an excessive number of leukocytes. Sometimes it is used in parallel with drug treatment. A significantly enlarged spleen is sometimes exposed to x-rays, this helps to reduce its size. When purulent inflammatory foci occur, antibiotics are used.

With the development of severe anemia, tolerant to cytostatics, or during therapy iron deficiency anemia Blood transfusion is indicated with appropriate iron supplements. Patients are subject to registration at the dispensary; they need regular examinations and monitoring of blood counts. Self-therapy chronic form myeloid leukemia is untenable and unacceptable.

Pathology progression

With the development of pathology, cytostatics are indicated. The extent of treatment depends on the phase of the disease. The occurrence of obvious symptoms (enlargement of organs, increase in the number of leukocytes in comparison with an earlier stage of pathology) is a reason for the use of primary restraining approaches. Patients are prescribed hydroxyurea in small doses on an outpatient basis, subject to monitoring blood counts. After remission of the disease, maintenance treatment is used.

Advanced stage of pathology

If the disease has reached an advanced stage, drug treatment carried out depending on the “risk group” ( hematological parameters). If the risks are low, treatment is initially carried out with one drug (monochemotherapy); if the risk is high, it is immediately recommended to use several drugs simultaneously (polychemotherapy).

Having completed the course of monochemotherapy, the same drug is first prescribed, but in a higher dosage. If blood counts improve, it is discontinued or the dosage is reduced. If the cytostatic used does not bring the expected effect within a month, treatment is carried out with another drug.

After a course of chemotherapy, maintenance treatment is carried out (the scheme is similar to the scheme of primary restraining therapy). Medicines that have proven effective during a course of treatment are used. Polychemotherapy is carried out at an increased degree of risk and at the last stage of CML. For blast crisis, therapy is similar to treatment acute leukemia. Polychemotherapy is carried out in short courses of 5-14 days. The duration of the breaks is 7-10 days.

Alpha interferon

Fundamentally new treatments for chronic myeloid leukemia include alpha-interferon, a growth factor antagonist. It inhibits the influence of megakaryocytes on the process of hematopoiesis and prevents the proliferation of granulocytes. In addition, alpha interferon activates antitumor immunity, creating conditions for the normalization of hematopoiesis.

Being a cytostatic medicine does not have a depressive effect on healthy cells. Treatment with alpha interferon can also cause cytogenetic remission - the absence of the Philadelphia chromosome. This does not even indicate remission, but the complete recovery of the patient.

There are no preventive measures for chronic myeloid leukemia. It is only possible to prevent exacerbations of pathology (maintenance treatment, prevention of insolation, colds). The average life expectancy for CML is three to five years, sometimes up to eight. After the development of blast crisis, the patient rarely manages to live more than a year.

The essence of the disease

Chronic myeloid leukemia (chronic myeloid leukemia, chronic myeloid leukemia, CML) is a disease in which there is excessive formation of granulocytes in the bone marrow and increased accumulation in the blood of both these cells themselves and their precursors. The word “chronic” in the name of the disease means that the process develops relatively slowly, unlike acute leukemia, and “myeloid” means that the process involves cells of the myeloid (rather than lymphoid) lineage of hematopoiesis.

Characteristic feature CML is the presence in leukemic cells of the so-called Philadelphia chromosome– a special chromosomal translocation. This translocation is designated as t(9;22) or, in more detail, as t(9;22)(q34;q11) - that is, a certain fragment of chromosome 22 changes places with a fragment of chromosome 9. As a result, a new, so-called chimeric, is formed. a gene (designated BCR-ABL), the “work” of which disrupts the regulation of cell division and maturation.

Chronic myeloid leukemia belongs to the group myeloproliferative diseases .

Incidence and risk factors

In adults, CML is one of the most common types of leukemia. Every year, 1-2 cases per 100 thousand population are registered. In children, it occurs significantly less frequently than in adults: about 2% of all cases of CML occur in childhood. Men get sick slightly more often than women.

Incidence increases with age and is higher among people exposed to ionizing radiation. Other factors (heredity, nutrition, ecology, bad habits) apparently do not play a significant role.

Signs and symptoms

Unlike acute leukemia, CML develops gradually and is divided into four stages: preclinical, chronic, progressive and blast crisis.

On initial stage the patient may not have any noticeable manifestations of the disease, and the disease may be suspected by chance, based on the results general analysis blood. This preclinical stage.

Then symptoms such as shortness of breath, fatigue, pallor, loss of appetite and weight, night sweats, and a feeling of heaviness in the left side due to an enlarged spleen appear and slowly increase. Fever and joint pain may occur due to the accumulation of blast cells. The phase of the disease in which symptoms are not very pronounced and develop slowly is called chronic .

In most patients, the chronic phase after some time - usually several years - enters the acceleration (acceleration). or progressive. The number of blast cells and mature granulocytes increases. The patient feels noticeable weakness, pain in the bones and an enlarged spleen; the liver also enlarges.

The most severe stage in the development of the disease is blast crisis. in which the content of blast cells is sharply increased and CML in its manifestations becomes similar to aggressive acute leukemia. Patients may experience high fever, bleeding, bone pain, difficult-to-treat infections, and leukemic skin lesions (leukemids). In rare cases, an enlarged spleen may rupture. Blast crisis – life-threatening and a difficult-to-treat condition.

Diagnostics

Often, CML is detected before any clinical signs appear, simply by an increased number of white blood cells (granulocytes) in a routine blood test. A characteristic feature of CML is an increase in the number of not only neutrophils. but also eosinophils and basophils. Mild to moderate anemia is common; platelet levels vary and may be elevated in some cases.

If CML is suspected, a bone marrow puncture is performed. The basis for diagnosing CML is the detection of the Philadelphia chromosome in cells. It can be done using cytogenetic research or molecular genetic analysis.

The Philadelphia chromosome can occur not only in CML, but also in some cases of acute lymphoblastic leukemia. Therefore, the diagnosis of CML is made based not only on its presence, but also on other clinical and laboratory manifestations described above.

Treatment

To treat CML in the chronic phase, a number of drugs are traditionally used that inhibit the progression of the disease, although they do not lead to a cure. Thus, busulfan and hydroxyurea (hydrea) allow you to control the level of white blood cells for some time. and the use of interferon alpha (sometimes in combination with cytarabine), if successful, significantly slows the progression of the disease. Definite clinical significance These drugs have been preserved to this day, but now there are much more effective modern drugs.

A specific agent that allows one to specifically “neutralize” the result of genetic damage in cells in CML is imatinib (Gleevec); This drug is significantly more effective than earlier drugs and is better tolerated. Imatinib can dramatically increase the duration and improve the quality of life of patients. Most patients must take Gleevec continuously from the moment of diagnosis: stopping treatment is associated with the risk of relapse. even if clinical and hematological remission has already been achieved.

Treatment with Gleevec is carried out on an outpatient basis, the medicine is taken in tablet form. The response to treatment is assessed at several levels: hematological (normalization clinical analysis blood), cytogenetic (disappearance or sharp decrease in the number of cells where the Philadelphia chromosome is detected by cytogenetic analysis) and molecular genetic (disappearance or sharp decrease in the number of cells where polymerase chain reaction can detect the chimeric BCR-ABL gene).

Gleevec is the basis of modern therapy for CML. Potent new drugs are also constantly being developed for patients intolerant or unresponsive to imatinib therapy. Currently, there are drugs dasatinib (Spricel) and nilotinib (Tasigna), which can help a significant proportion of these patients.

The question of treatment in the blast crisis phase is difficult, since the disease at this stage is already difficult to treat. Possible various options, including both the above medications and, for example, the use of approaches similar to induction therapy for acute leukemia.

Except drug therapy CML, auxiliary procedures may also be needed. Thus, with a very high level of leukocytes, when their aggregation inside the vessels and increased blood viscosity interfere with the normal blood supply to the internal organs, partial removal of these cells using the apheresis procedure (leukapheresis) can be used.

Unfortunately, as already mentioned, during therapy with Gleevec and other medicines Some cells with a genetic defect may remain in the bone marrow (minimal residual disease), which means that a complete cure is not achieved. Therefore, young patients with CML in the presence of a compatible donor. especially related ones, in some cases a bone marrow transplant is indicated - despite the risks associated with this procedure. If successful, transplantation leads to complete cure of CML.

Forecast

The prognosis for CML depends on the patient’s age and the number of blast cells. response to therapy and other factors. In general, new drugs such as imatinib can extend life expectancy for most patients by many years while significantly improving quality of life.

With allogeneic bone marrow transplantation, there is a significant risk of post-transplant complications (graft-versus-host disease, toxic effects of chemotherapy on internal organs, infectious and other problems), but if successful, complete recovery occurs.

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