Chronic myeloid leukemia - symptoms, blood tests, treatment and life expectancy. How long do they live with chronic myeloid leukemia, and how does the stage of the disease affect life expectancy Stages of myeloid leukemia

Until recently, it was generally accepted that chronic myeloid leukemia was a disease that was more common in older men. Now doctors have come to the conclusion that both women and men have an equal chance of becoming victims of this disease. Why does this disease occur, who is at risk, and can it be cured?

Essence of the disease

In the human body, the bone marrow is responsible for the processes of hematopoiesis. Blood cells are produced there - red blood cells, platelets and leukocytes. The hemolymph contains the most leukocytes. They are responsible for immunity. Chronic myeloid leukemia leads to a failure of these processes.

In a person suffering from this type of leukemia, the bone marrow produces pathological leukocytes - oncologists call them blasts. They begin to multiply uncontrollably and leave the bone marrow before they have time to mature. Essentially, these are “immature” leukocytes that cannot perform protective functions.

Gradually they spread through the vessels to all human organs. The content of normal white blood cells in the plasma gradually decreases. The blasts themselves do not die - the liver and spleen cannot destroy them. Due to the lack of leukocytes, the human immune system stops fighting allergens, viruses and other negative factors.

Causes of the disease

In the vast majority of cases, chronic myeloid leukemia is caused by a gene mutation – a chromosomal translocation, which is commonly called the “Philadelphia chromosome”.

Technically, the process can be described as follows: chromosome 22 loses one of the fragments, which fuses with chromosome 9. A fragment of chromosome 9 attaches to chromosome 22. This causes a malfunction of genes, and then the immune system.

Experts say that the occurrence of this type of leukemia is also influenced by:

• exposure to radiation. After the nuclear attack on Hiroshima and Nagasaki, the incidence of CML in residents of Japanese cities increased significantly;
• exposure to certain chemicals - alkenes, alcohols, aldehydes. Smoking has a negative effect on the condition of patients;
• taking certain medications - cytostatics, if cancer patients take them along with undergoing radiation therapy;
• radiotherapy;
• hereditary genetic diseases - Klinefelter syndrome, Down syndrome;
• diseases of viral origin.

Important! CML mainly affects people over 30-40 years of age, and their risk of developing the disease increases with age, up to 80 years of age. It is diagnosed very rarely in children.

There is, on average, one to one and a half cases of this disease per 100 thousand inhabitants of the Earth. In children, this figure is 0.1-0.5 cases per 100 thousand people.

How does the disease progress?

Doctors distinguish three stages of development of chronic myeloid leukemia:

• chronic stage;
• acceleration stage;
• terminal stage.

The first phase usually lasts two to three years and is most often asymptomatic. The manifestation of this disease is atypical and may not differ from a general malaise. The disease is diagnosed accidentally, for example, when a person comes for a general blood test.

The first signs of the disease are general malaise, a feeling of fullness in the abdomen, heaviness in the left hypochondrium, decreased ability to work, low hemoglobin. Upon palpation, the doctor will find an enlarged spleen due to the tumor, and a blood test will reveal an excess of granulocytes and platelets. Men often experience long, painful erections.

The spleen enlarges, the person experiences problems with appetite, quickly becomes full, and feels pain radiating to the back in the left side of the abdominal cavity.

Sometimes in the initial phase the function of platelets is disrupted - their level increases, blood clotting increases. A person develops thrombosis, which is associated with headaches and dizziness. Sometimes the patient experiences shortness of breath with even minimal physical exertion.

The second, accelerated stage occurs when a person’s general condition worsens, symptoms become more pronounced, and laboratory tests record changes in blood composition.

The person loses weight, becomes weak, experiences dizziness and bleeding, and the temperature rises.

The body produces more and more myelocytes and white blood cells, and blasts appear in the bones. The body reacts to this by releasing histamine, so the patient begins to feel fever and itching. He begins to sweat heavily, especially at night.

The duration of the acceleration phase is from one to one and a half years. Sometimes a person begins to feel unwell only in the second stage and goes to the doctor when the disease has already progressed.

The third, terminal phase occurs when the disease enters the acute stage.

A blast crisis occurs in chronic meyloid leukemia, when cells with pathology almost completely replace healthy ones in the organ responsible for hematopoiesis.

The acute form of chronic myeloid leukemia has the following symptoms:

• severe weakness;
• temperature rise to 39-40 degrees;
• a person begins to rapidly lose weight;
• the patient feels joint pain;
• hypohidrosis;
• hemorrhages and bleeding.

Acute myeloid leukemia often leads to splenic infarction - the tumor increases the risk of splenic rupture.

The number of myeloblasts and lymphoblasts is growing. Blasts can turn into a malignant tumor - myeloid sarcoma.

Chronic myeloid leukemia at the third stage is incurable, and only palliative therapy will prolong the patient’s life by several months.

How to diagnose the disease?

Since the disease initially has nonspecific symptoms, it is often discovered almost by accident when a person comes, for example, to take a general blood test.

If a hematologist suspects cancer, he must not only conduct a survey and examine his lymph nodes, but also palpate the abdomen to see if the spleen is enlarged and if there is a tumor in it. To confirm or refute suspicions, the subject is sent for an ultrasound of the spleen and liver, as well as a genetic study.

Methods for diagnosing chronic myeloid leukemia:

• general and ;
• bone marrow biopsy;
• cytogenetic and cytochemical research;
• Ultrasound of the abdominal organs, MRI, CT.

A general detailed blood test allows you to trace the dynamics of the development of all its components.

At the first stage, it will determine the level of “normal” and “immature” white blood cells, granulocytes and platelets.

The acceleration phase is characterized by an increase in the level of leukocytes, an increase in the proportion of “immature” leukocytes to 19 percent, as well as a change in the level of platelets.

If the proportion of blasts exceeds 20 percent and the platelet count decreases, then the third stage of the disease has arrived.

Biochemical analysis will help determine the presence in the blood of substances that are characteristic of this disease. We are talking about uric acid, vitamin B12, transcobalamin and others. Biochemistry determines whether there are malfunctions in the functioning of lymphoid organs.

If a person has chronic myeloid leukemia in the blood, the following occurs:

• significant increase;
• the predominance of “immature” forms of leukocytes - blast cells, myelocytes, pro- and metamyelocytes.
• increased content of baso- and eosinophils.

A biopsy is necessary to determine the presence of abnormal cells. The doctor uses a special needle to collect brain tissue (a suitable place for puncture is the femur).

Cytochemical testing allows one to distinguish chronic myeloid leukemia from other types of leukemia. Doctors add reagents to the blood and tissue obtained from a biopsy and see how the blood cells behave.

Ultrasound and MRI give an idea of ​​the size of the abdominal organs. These studies help differentiate the disease from other types of leukemia.

Cytogenetic research helps to find abnormal chromosomes in blood cells. This method allows not only to reliably diagnose the disease, but also to predict its development. To detect an abnormal or “Philadelphia” chromosome, the hybridization method is used.

Treatment of the disease

Treatment of chronic myeloid leukemia has two main goals: to reduce the size of the spleen and to stop the bone marrow from producing abnormal cells.

Hematologic oncologists use four main treatment methods:

1. Radiation therapy;
2. Bone marrow transplantation;
3. Splenectomy (removal of the spleen);
4. Leukapheresis.

Depends on the individual characteristics of the patient’s body, as well as on the severity of the disease and symptoms.

In the early stages of treating leukemia, doctors prescribe drugs to their patients to strengthen the body, vitamins and a balanced diet. A person must also adhere to a work and rest schedule.

In the first stages, if the level of leukocytes increases, doctors often prescribe busulfan to their patients. If this gives results, the patient is transferred to maintenance therapy.

In late phases, doctors use traditional drugs: Cytosar, Myelosan, Dazanitib, or modern drugs like Gleevec and Sprycel. These drugs target the oncogene. Together with them, patients are prescribed interferon. It should strengthen the human immune system.

Carefully! The doctor prescribes the regimen and dosage of medications. The patient is prohibited from doing this on his own.

Chemotherapy usually comes with side effects. Taking medications often leads to digestive upset, causes allergic reactions and convulsions, reduces blood clotting, provokes neuroses and depression, and leads to hair loss.

If the disease is in a progressive phase, hematologists prescribe several drugs at the same time. The duration of intensive chemotherapy depends on how quickly laboratory values ​​return to normal. Typically, a cancer patient must undergo three to four courses of chemotherapy per year.

If taking cytostatics and chemotherapy do not produce results, and the disease continues to progress, the hematologist refers his patient to radiation therapy.

Indications for it are:

• an increase in tumor in the bone marrow;
• enlarged spleen and liver;
• if blasts enter the tubular bones.

The oncologist must determine the regimen and dose of radiation. The rays affect the tumor in the spleen. This stops the growth of oncogenes or completely destroys them. Radiation therapy also helps relieve joint pain.

Irradiation is used at the accelerated stage of the disease.

Bone marrow transplantation is one of the most effective treatment options. It guarantees long-term remission for 70 percent of patients.

Bone marrow transplantation is a fairly expensive treatment method. It consists of several stages:

1. Donor selection. The ideal option is when a close relative of a cancer patient becomes a donor. If he does not have brothers and sisters, then he has to be looked for in special databases. This is quite difficult to do, since the chances that foreign elements will take root in the patient’s body are less than if the donor were a member of his family. Sometimes it becomes the patient himself. Doctors can transplant peripheral cells into his bone marrow. The only risk is associated with the high probability that blasts will get there along with healthy leukocytes.
2. Preparing the patient. Before surgery, the patient must undergo chemotherapy and radiation. This will kill a significant portion of the pathological cells and increase the chances that the donor cells will take root in the body.
3. Transplantation. Donor cells are injected into a vein using a special catheter. They first move through the vascular system, then begin to act in the bone marrow. After transplantation, the doctor prescribes antiviral and anti-inflammatory drugs so that the donor material is not rejected.
4. Working with the immune system. It is not immediately possible to understand whether donor cells have taken root in the body. Two to four weeks should pass after the transplant. Since the person’s immunity is at zero, he is ordered to stay in the hospital. He receives antibiotics and is protected from contact with infectious agents. At this stage, the patient’s body temperature rises, and chronic diseases may worsen.
5. Post-transplantation period. When it is clear that foreign leukocytes have been accepted by the bone marrow, the patient's condition improves. Full recovery takes several months and even years. All this time, a person must be observed by an oncologist and receive vaccinations, since his immune system will not be able to cope with many diseases. A special vaccine has been developed for people with weakened immune systems.

Transplantation is usually performed in the first stage.

Removal of the spleen, or splenectomy, is used in the terminal stage if:

• there has been an infarction of the spleen, or there is a threat of rupture;
• if the organ has enlarged so much that it interferes with the functioning of neighboring abdominal organs.

What is leukapheresis? Leukocytopheresis is a procedure aimed at clearing pathological leukocytes. A certain amount of the patient's blood is forced through a special machine, where cancer cells are removed from it.

This treatment usually complements chemotherapy. Leukapheresis is performed when the disease progresses.

Survival Projections

The healing of a cancer patient and his life expectancy depend on several factors.

The likelihood of recovery depends on the stage at which chronic myeloid leukemia was diagnosed. The sooner this is done, the better.

The chances of healing are reduced if the abdominal organs are seriously enlarged and protrude from under the edges of the costal arch.

Negative signs include leukocytosis, thrombocytopenia, and an increase in the content of blast cells.

The more manifestations and symptoms a patient has, the less favorable the prognosis will be.

With timely intervention, remission occurs in 70 percent of cases. After healing, the chances are high that the patient will live for several more decades.

Death most often occurs in the accelerated and terminal stages; about seven percent of patients with chronic myeloid leukemia die in the first year after they were diagnosed with CML. The causes of death are severe bleeding and infectious complications due to weakened immunity.

Palliative therapy at the last stage after blast crisis prolongs the patient’s life, at most, by six months. The life expectancy of a cancer patient is calculated in a year if remission occurs after a blast crisis.

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.

Excessive formation of uric acid during the breakdown of neutrophil nuclei 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: elevated uric acid levels.

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

Indications for local radiation therapy are giant splenomegaly with perisplenitis, tumor-like leukemides. 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) is a myeloproliferative chronic disease 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 demonstrates 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 corresponds to three stages of chronic myeloid leukemia in clinical presentation.

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

Stage II - extensive - 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, degenerative changes in internal organs, pronounced changes in the blood (anemia, lombopenia). The terminal stage of CML is characterized by the 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 crisis 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, proliferation of leukemic cells in the bone marrow, spleen and liver (sweating, weakness, weight loss, heaviness and pain in the spleen and liver), ossalgia;

B) enlargement of the liver and spleen;

B) 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 disruption of the procoagulant and platelet components of hemostasis);

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

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

The different severity of syndromes at different stages of the disease causes a rather 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 with a variety of diseases, THEREFORE they cannot be considered at stage I as specific to 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*KTepa and bone pain, they can direct the doctor to a myeloproliferative disease.

In the terminal stage of the disease, some 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 drugs that, until now, improved the general condition and reduced 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 of the 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 50 109/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 a small the number of blasts is up to 1-3%. The bone marrow is rich in cellular elements with a predominance of elements of the granulocytic series. The number of eosinophils, basophils, granulocytes can be increased.

In stage II, the number of leukocytes is 50-500 109/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 50,109/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.

The functional properties of leukocytes and their enzymatic content are changed: the activity of neutrophil alkaline phosphatase is reduced, and the ability to phagocytosis is impaired. When puncturing an enlarged spleen at an advanced stage of the disease, a predominance of myeloid cells is revealed (which is never normally found). 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

0th blood (the total number of blasts and promyelocytes is equal to 20% of 1C, 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 20-109/l;

The appearance in the leukocyte formula of proliferating forms (myeloblasts 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 an increase in the activity of neutrophil alkaline phosphatase (instead of its decrease 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 (with good health, but undoubted changes in the peripheral blood and bone marrow), we need general restorative therapy, proper nutrition, adherence to the

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.

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

The number of leukocytes in comparison with the previous period is determined by so-called primary-containing therapy. Conventional treatment begins when the leukocyte count is 50-70-109/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 200109/l, blasts more than 3%, the sum of blasts and myelocytes in the blood more than 20%, the number of basophils in the blood more than 10%"¦

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

3) thrombocytosis more than 500 109/l or thrombocytopenia less than 100 109/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 or 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: if the number of leukocytes and platelets decreases, the dose of the drug is reduced, and if the leukocyte count is 10-20 109/l and platelet count is 100-109/l, the drug is discontinued. If previously 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 at high 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 treating CML have emerged - the cytokine α-interferon (α-IFN). The fact is that during the process of myeloid proliferation, megakaryocytes and platelets release a large number of growth factors, which themselves contribute to the further proliferation of mutant pluripotent and oligopotent stem cells, and in addition, stromal cells. All this leads to further progression of the disease, as well as the development of fibrosis and changes in the bone marrow. Meanwhile, it has been proven that a-IFN, in its chemical structure and functional properties, is an antagonist of growth factors; it secretes substances that inhibit the stimulating effect of megakaryocytes on hematopoiesis and have antiproliferative activity towards the parent cells of hematopoiesis; in addition, α-IFN stimulates antitumor immunity ^ Consequently, conditions are created for maintaining 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 is used - 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 U)" allowing to achieve hematological remission -

And v many sick people. When treated with this drug, a “type-like” syndrome may appear - fever, headache, muscle soreness, general poor health, but taking paracetamol eliminates 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/(m2-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.

When the spleen is significantly enlarged, X-ray irradiation is sometimes carried out, 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 of the disease, which consists of preventing exacerbations of the disease (maintenance therapy, avoiding sun exposure, colds, etc.).

Erythremia (polycythemia vera, Vaquez disease)

Erythremia (ER) is a myeloproliferative disease, chronic

Icical, benign current leukemia, in which there is

Increased formation of erythrocytes, as well as neutrophilic leukocytes

Ov and platelets. The source of tumor growth is the progenitor cell.

Ca myelopoiesis.

The incidence of erythremia is about 0.6 per 10,000 population. Both men and women get sick equally often. Erythremia is a disease of older people: the average age of those affected is 55-60 years, but the disease can occur at any age.

Etiology. The reasons for the development of the disease are unknown.

Pathogenesis. Erythremia is based on tumor clonal proliferation of all three hematopoietic lineages - red, granulocytic and megakaryocytic, but the growth of the red lineage dominates. In this regard, the main substrate of the tumor is red blood cells maturing in excess. Foci of myeloid hematopoiesis appear in the spleen and liver (which never happens normally). An increased number of red blood cells and platelets in the peripheral blood reduces the speed of blood flow, increases the viscosity and coagulability of the blood, which causes the appearance of a number of clinical symptoms.

Classification. The stage of the disease, the involvement of the spleen in the pathological process and the subsequent transformation of erythremia into other diseases of the blood system are taken into account.

Stage I - initial: hemoglobin content is at the upper limit of normal, a slight increase in the mass of circulating red blood cells, the spleen is slightly enlarged (due to blood overflow) or without changes. Blood pressure is normal or slightly elevated, and focal bone marrow hyperplasia is noted in the iliac trephine specimen. The duration of stage I can exceed 5 years.

Stage II - extensive: phase A - without myeloid metaplasia of the spleen (a simple version of plethora without splenomegaly). Total three-fold hyperplasia of the bone marrow. Absence of extramedullary hematopoiesis; phase B - with myeloid metaplasia of the spleen. Major myeloproliferative syndrome: pancytosis in the peripheral blood, in the bone marrow there is panmyelosis with or without focal myelofibrosis, myeloid metaplasia of the spleen with or without fibrosis.

Stage III - terminal: degeneration of a benign tumor into a malignant one (myelofibrosis with anemization, chronic myelo-leukemia, acute leukemia). Myelofibrosis develops in almost all patients for more than 10-15 years; it reflects the natural evolution of the disease. A sign of myelofibrosis is cytopenia (anemia, thrombocytopenia, and less commonly, leukopenia). The development of chronic myeloid leukemia is manifested by an increase in leukocytosis, an increase (or appearance) in the peripheral blood of myelocytes, promyelocytes, as well as the detection of the Ph chromosome in blood and bone marrow cells.

Acute leukemia usually develops in patients treated with cytostatics and radioactive phosphorus.

Anemia in patients with erythremia may be associated with frequent bloodletting, increased deposition of red blood cells, as well as their hemolysis.

Clinical picture. Erythremia manifests itself in two major syndromes.

Plethoric syndrome is caused by an increased content of red blood cells, as well as leukocytes and platelets (plethora - plethora). This syndrome is caused by: 1) the appearance of subjective symptoms; 2) disorders of the cardiovascular system; 3) changes in laboratory parameters.

1. Subjective symptoms of plethoric syndrome include headaches, dizziness, blurred vision, angina pectoris, skin itching, erythromelalgia (sudden onset of hyperemia with systemic

A pleasant tint of the skin of the fingers, accompanied by sharp pain and burning), possible sensations of numbness and chilliness of the limbs.

2. Disorders of the cardiovascular system are manifested in changes in the color of the skin and visible mucous membranes, such as erythrozzanosis, peculiarities of the color of the mucous membrane at the point of transition of the soft palate to the hard palate (Kuperman's symptom), hypertension, the development of thrombosis, and, less often, bleeding. In addition to thrombosis, swelling of the legs and erythromelalgia are possible. Circulatory disorders in the arterial system can lead to serious complications: acute myocardial infarction, strokes, visual impairment, and renal artery thrombosis.

3. Changes in laboratory parameters: an increase in the content of hemoglobin and red blood cells, an increase in hematocrit and blood viscosity, moderate leukocytosis with a shift in the leukocyte formula to the left, thrombocytosis, a sharp slowdown in ESR.

Myeloproliferative syndrome is caused by hyperplasia of all three hematopoietic lineages in the bone marrow and extramedullary. It includes: 1) subjective symptoms, 2) splenomegaly and (or) hepatomegaly, 3) changes in laboratory parameters.

1. Subjective symptoms: weakness, sweating, increased body temperature, bone pain, heaviness or pain in the left hypochondrium (due to

Splenomegaly).

2. Splenomegaly is explained not only by myeloid metaplasia of the organ (the appearance of foci of extramedullary hematopoiesis), but also by blood stagnation. Less commonly, liver enlargement is observed.

3. Among the laboratory indicators, deviations from the physiological norm in the peripheral blood have the greatest diagnostic significance: pancytosis, often with a shift in the leukocyte formula to the left; trephine biopsy reveals three-line hyperplasia of the bone marrow, and in the puncture of the spleen - foci of myeloid metaplasia of the organ.

The different severity of syndromes at different stages of the disease causes extreme variability in the clinical picture. It is possible to observe patients with undoubted erythremia, who show almost no complaints and are fully able to work, and patients with severe damage to internal organs who require therapy and have lost their ability to work.

At stage I of the diagnostic search in the initial stage of the disease, patients may not present any complaints. As the disease progresses, complaints are associated with the presence and severity of plethora and the myeloproliferative process. The most common complaints are of a “pletoric” nature, caused by increased blood supply to the vessels and functional neurovascular disorders (headaches, erythromelalgia, blurred vision, etc.). All these symptoms may be associated with other diseases, which must be clarified during further examination of the patient.

Complaints caused by the presence of myeloproliferative syndrome (sweating, heaviness in the left hypochondrium, bone pain, increased body temperature) are also nonspecific for erythremia. The skin itching that appears after taking water treatments is quite typical. This symptom is observed in 55% of patients in the advanced stage and is explained by overproduction of basophils and histaminemia. The nature of urticaria, observed in 5-7% of patients, is similar.

The listed symptoms are important for determining the stage of erythremia: usually they indicate the transition of the disease to full-blown

Or the terminal stage with the development of myelofibrosis as the most common outcome of erythremia.

Patients may have a history of complications of the disease such as strokes and myocardial infarction. Sometimes the disease debuts with precisely these complications, and the true cause of their development - erythremia - is revealed when examining a patient for a stroke or myocardial infarction

Indications of previous treatment with radioactive phosphorus, cytostatics or bloodletting may suggest the presence of some kind of tumor blood disease. A decrease in the symptoms of plethoric syndrome during treatment with these drugs suggests erythremia.

At stage II of the diagnostic search, it is possible to identify distinct symptoms only in stage II (advanced) of the disease. The main signs of plethoric syndrome are found: erythrocyanosis, injected conjunctival vessels (“rabbit eyes”), a distinct color border at the transition point of the hard palate to the soft palate. You can identify symptoms of erythro-melalgia: swelling of the tips of the fingers, feet, lower third of the leg, accompanied by local hyperemia and a sharp burning sensation.

When examining the cardiovascular system, hypertension and enlargement of the left ventricle are diagnosed, in the advanced stage of the disease - “motley legs” (changes in the color of the skin of the legs, mainly their distal part) in the form of areas of pigmentation of varying intensity, caused by impaired venous circulation.

When palpating the abdomen, one can detect an enlarged spleen, which is one of the characteristic signs of the disease. Enlargement of the spleen may be due to: 1) increased deposition of blood elements; 2) “working” hypertrophy due to an increase in its sequestering function; 3) extramedullary hematopoiesis (myeloid metaplasia with a predominance of erythropoiesis). These reasons are often combined. Liver enlargement is due to similar reasons, as well as the development of fibrosis and nonspecific reactive hepatitis. It should be borne in mind that hepatomegaly can be observed with a malignant liver tumor with the development of secondary erythrocytosis.

Complications of erythremia in the form of cerebral vascular thrombosis are expressed by a number of focal symptoms identified during the study

However, even at stage II it is impossible to definitively diagnose erythremia, since many of its symptoms can be associated with symptomatic erythrocytosis. In addition, symptoms such as hypertension, splenomegaly and hepatomegaly are characteristic of a wide variety of diseases.

In this regard, stage III of the diagnostic search becomes crucial, as it allows: a) to make a final diagnosis; b) clarify the stage of erythremia; c) identify complications; d) monitor treatment.

Analysis of peripheral blood reveals erythrocytosis, an increase in hemoglobin content and hematocrit, which, however, also occurs with symptomatic erythrocytosis. An increase in hemoglobin levels in combination with erythrocytosis, leukocytosis and thrombocytosis is of diagnostic significance. When examining the leukocyte formula, a shift to the left to immature forms of granulocytes is detected. If changes in peripheral blood are minor or the data are inconclusive (for example, erythrocytosis is not combined with thrombocytosis), then a bone marrow examination (trephine biopsy) must be performed. Presence of total-442 in trepanate

Three-line hyperplasia of the bone marrow with a predominance of formen-Hbix elements of erythropoiesis, replacement of adipose tissue with a red line of bone marrow make it possible to make a final diagnosis. The expansion of the “bridgehead” of hematopoiesis is also detected using radionuclide bone scanning with 32P. Histochemical examination reveals increased activity of neutrophil alkaline phosphatase.

Complications. The course of erythremia is complicated by: 1) vascular thrombosis (cerebral, coronary, peripheral arteries); 2) hemorrhagic syndrome: bleeding after minor surgical interventions (tooth extraction), from the vessels of the digestive tract, hemorrhoids, which is caused by poor retraction of the blood clot due to changes in the functional properties of platelets; 3) endogenous uricemia and uricosuria (due to increased cell death at the nuclear prestages of their maturation), which is manifested by symptoms of urolithiasis and gouty arthritis.

The outcomes of the disease are the situations indicated in stage III of the disease (myelofibrosis, chronic myelogenous leukemia, acute leukemia, anemia).

Diagnostics. Erythremia can be suspected in individuals with persistent erythrocytosis in combination with neutrophilic leukocytosis, thrombocytosis in the absence of diseases (or conditions) that could cause erythrocytosis.

Diagnostic criteria for erythremia (in the advanced stage) are:

Increase in the mass of circulating red blood cells.

Normal arterial blood oxygen saturation (more than 92%).

Leukocytosis is more than 12,109/l (in the absence of obvious reasons for the appearance of leukocytosis).

Thrombocytosis more than 400-109/l.

Increased levels of neutrophil alkaline phosphatase (in the absence of infection).

Increase in unsaturated vitamin B12-binding capacity of blood serum.

The diagnosis of ER is reliable in the presence of three signs of category A or two signs of category A and one sign of category B.

Difficulties in making a diagnosis are due to the development of so-called symptomatic erythrocytosis in a number of diseases. Absolute and relative erythrocytoses are distinguished. With absolute erythrocytosis, an increase in the mass of circulating erythrocytes and increased erythropoiesis are noted. Relative erythrocytosis is characterized by a decrease in the volume of circulating plasma and a normal mass of circulating erythrocytes. Relative erythrocytosis is often detected in men suffering from hypertension, obesity, neurasthenia, and taking diuretics. Secondary absolute erythrocytosis develops in smokers; it is caused by an increase in the content of carbon monoxide in the blood.

Reasons for the development of symptomatic erythrocytosis: 1) generalized tissue hypoxia (pulmonary pathology, heart disease, hemoglobinopathies, obesity, etc.); 2) paraneoplastic reactions (Nochek tumors, tumors of the cortex and medulla of the adrenal glands, pituitary gland, ovaries, vascular tumors, tumors of other organs); 3) renal ischemia

(renal artery stenosis, hydronephrosis, polycystic disease and other kidney anomalies); 4) unknown causes (CNS disease, portal hypertension).

Relative erythrocytosis is observed during exicosis (dehydration due to diarrhea, vomiting, excessive sweating, etc.). Differential diagnosis is based on taking into account the entire clinical picture. In difficult cases, it is necessary to examine the content of erythropoietin in the blood; with erythremia it does not increase.

The formulation of a detailed clinical diagnosis includes information about 1) the stage of the disease; 2) presence of complications; 3) phase of the process (exacerbation or remission); 4) the presence of pronounced syndromes (portal hypertension, hypertension, etc.).

Treatment. The entire complex of therapeutic measures for ER appears to be as follows.

In the advanced stage of the disease, in the presence of plethoric syndrome, but without leuko- and thrombocytosis, bloodletting is used as an independent method of therapy, and it is necessary to reduce the hematocrit level to normal values ​​(less than 45%). 400-500 ml of blood are taken every other day (in a hospital setting) or after 2 days (in a clinic setting). To prevent thrombosis (develop as a result of bloodletting, and also as a complication of erythremia), acetylsalicylic acid is prescribed at a dose of 0.5-1 g/day the day before and on the day of bloodletting, and then for 1-2 weeks after the end of bloodletting. In addition to acetylsalicylic acid, other disaggregants are prescribed - ticlid, plavike, pentoxifylline. Before bloodletting, to prevent pulmonary embolism, it is advisable to administer 5000 units of heparin intravenously (through a Dufault needle), as well as 5000 units of heparin under the skin of the abdomen 2 times a day for several days after bloodletting. In case of poor tolerance to bloodletting, observed in persons with severe cerebral atherosclerosis, exfusion is limited to 350 ml (2 times a week). When bleeding, it is necessary to reduce hemoglobin to 150 g/l.

If bloodletting is not effective enough, as well as in forms of the disease that occur with pancytosis and splenomegaly, cytostatic therapy is prescribed. The age of patients over 55 years expands the indications for the use of cytostatics. Indirect indications for cytostatic therapy are other signs of myeloproliferative syndrome (itching), as well as the severity of the disease, visceral vascular complications (stroke, myocardial infarction), and exhaustion.

Contraindications to cytostatic therapy: young age of patients, refractoriness to treatment at previous stages, as well as excessively active cytostatic therapy in the past due to fear of the disease transitioning to the anemia phase. The effect of cytostatic therapy should be assessed 3 months after the end of treatment; this is explained by the fact that red blood cells produced before treatment live on average about 2-3 months. The decrease in the number of leukocytes and platelets occurs much earlier, according to their life span. The criterion for the effectiveness of cytostatic therapy is the achievement of hematological remission (complete, when all blood parameters are normalized, or partial, in which the number of red blood cells, leukocytes and/or platelets remains slightly elevated).

Of the cytostatic drugs at the first stage, hydroxyurea (hydrea) is usually prescribed at a dose of 30-50 mg/(kg day) (2-3 capsules per

Day). During treatment, it is necessary to monitor the number of leukocytes. Hydrea is combined with α-interferon at a dose of 3-5 million IU subcutaneously 3-7 times a week for a long time (at least a year), which allows the relief of thrombocytosis, plethora, and skin itching.

For hyperthrombocytosis, anagrelide is used.

The outcomes of erythremia (myelofibrosis, acute leukemia, chronic myeloid leukemia) are influenced according to the principles of treatment of these diseases: for myelofibrosis, anabolic steroids, nitostatics and red blood cell transfusions are used; for acute leukemia, polychemotherapy is indicated, for chronic myeloid leukemia - cytostatic drugs.

Symptomatic therapy for attacks of erythromelalgia is carried out with the help of antiplatelet agents, non-steroidal anti-inflammatory drugs (acetylsalicylic acid, indomethacin). Arterial hypertension and angina attacks are eliminated in accordance with the rules for the treatment of these conditions.

For complications of erythremia by vascular thrombosis, anticoagulant and antiplatelet therapy is used.

Patients with erythremia are registered at the dispensary with the frequency of visiting a doctor and the appointment of peripheral blood tests once every 3 months.

Forecast. With uncomplicated erythremia, life expectancy can reach 15-20 years (further complications arise). If complications from the cardiovascular system develop early enough or the disease progresses, life expectancy is reduced. Timely initiation of therapy extends life expectancy, although this is not observed in all cases.

Prevention. There are no radical measures to prevent the disease, and therefore we can only talk about secondary prevention, which consists of dynamic monitoring of patients and anti-relapse therapy.

– 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 develop. The diagnosis is established taking into account the medical history, clinical picture and laboratory data. Treatment – ​​chemotherapy, radiotherapy, bone marrow transplant.

General information

Chronic myeloid leukemia is an oncological disease that occurs as a result of a chromosomal mutation with damage to pluripotent 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 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 low-symptomatic course, it may become an accidental finding during a blood test taken in connection with another disease or during a routine 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 of 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 of chronic myeloid leukemia is 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, severe complications develop, 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, fatigue, 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.

A blast crisis is accompanied by a sharp deterioration in the 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 develop.

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. To clarify the diagnosis, data from a histological examination of the material obtained during sternal puncture of the bone marrow can be used, but 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 the severity of 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 pronounced splenomegaly, accompanied by dysfunction of the abdominal organs.

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. 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 figure can increase to several decades.

In modern times, tumor diseases of the blood are quite common among people of different ages and genders, with chronic myeloid leukemia (CML) observed in every fifth case. This pathology is a dangerous oncological disease and bone marrow stem cells, which lose the ability to fulfill their purpose and begin to actively multiply, disrupting the activity of the hematopoietic system. If not treated in a timely manner, the pathology can lead to death.

Description of the disease

Chronic myeloid leukemia is a pathology that affects stem cells as a result of a gene mutation in immature myeloid cells that form red blood cells, platelets, etc. For this reason, an abnormal gene appears in the human body, which turns healthy blood cells into leukemia (blasts) in the bone marrow. After some time, bone marrow growth stops, and blasts spread through the bloodstream throughout the body, affecting internal organs. This pathology is popularly called leukemia, at the initial stage of development of which the number of leukocytes and basophils increases.

Note! CML develops gradually over a long period of time. The main danger in this case is the fact that without special therapy the disease takes on an acute form, as a result of which the patient dies within a few months.

Epidemiology

Myeloid leukemia develops in every fifth case of all tumor blood diseases. Worldwide, the disease occurs in one person in a hundred thousand. This pathology is observed to the same extent in both men and women, most often it is diagnosed in people aged thirty to forty years. The disease is found very rarely in children. The countries of North America and Europe are in third place in the number of patients with this disease, Japan is in second place. Over the past few decades, epidemiological data on chronic myelocytic leukemia have not changed.

Causes of oncology

Modern medicine has not yet fully studied the causes of the development of myeloid leukemia. Possible causes include:

• an abnormal mutation of a stem cell, which begins to create similar blood cells (clones), which over time end up in internal organs and tissues;
• exposure to toxins and radiation on the body;
• results of radiation or chemotherapy for the treatment of other cancer;
• long-term use of medications whose action is aimed at eliminating tumors;
• infectious and viral diseases, Down or Klinefelter syndrome;
• hereditary predisposition when there is a mutation of chromosomes 9 and 22.

Due to chromosome mutations, new malignant DNA appears in bone marrow cells, which over time replaces healthy cells. New cells - clones begin to actively multiply uncontrollably, they do not die, they enter the blood from the bone marrow. In this case, there is a decrease in the number of mature leukocytes, and a predominance of immature leukocytes, which disrupt blood functions.

Stages of disease development

Chronic myeloid leukemia has three stages of development:

1. The chronic stage develops in the absence of timely treatment; the disease at this stage is diagnosed in 85% of patients. During this period, stability in the patient’s condition is observed, signs of pathology appear in minimal quantities and do not cause discomfort. The duration of this stage is three to four years, depending on how early treatment was started. CML is usually discovered incidentally during a blood test. If treatment is not started on time, the next stage of the disease occurs.
2. The accelerated stage, during which the active growth of abnormal blood cells begins. This phase lasts about one year, and the development of new pathologies in addition to the abnormal chromosome is possible.

Note! The number of immature leukocytes at this stage is constantly increasing, but it is possible to return the disease to the chronic phase with proper treatment. Otherwise, the last stage of the disease develops.

1. Blast crisis or end stage, which is the last phase of the disease, is characterized by the presence of new chromosome abnormalities. Here the bone marrow is completely replaced by pathological cells. This phase of the disease is similar to acute leukemia; if treatment is ineffective, the prognosis is unfavorable, and the disease ends in death. The blast crisis usually lasts about six months.

Some patients are already at the terminal stage of pathology when diagnosed, so the risk of death in this case is very high.

Symptoms and signs of pathology

At the initial stage of development, the disease does not show symptoms. Sometimes general weakness and fatigue may occur. As a rule, patients do not pay attention to these signs and do not go to a medical facility. Pathology in the chronic phase can be detected through a blood test.

Over time, a person begins to lose weight, loses appetite, and sweats during sleep. Then pain appears under the left rib, which is caused by an enlarged spleen. For the same reason, the lungs and stomach are compressed, which leads to breathing problems and pain in the head area. The level of hemoglobin and platelets in the blood decreases significantly, so there is a risk of developing blood clots, myocardial infarction, stroke or splenic infarction, and visual impairment.

Then the disease enters the acceleration phase. In this case, the person begins to feel obvious signs of pathology. He experiences pain in the bones and joints, increased body temperature, enlarged abdomen due to pathology of the spleen, and intoxication of the body. Over time, itching of the skin and a feeling of heat appear.

Acute myeloblastic leukemia (AML), which appears at the terminal stage, is characterized by an increase in temperature to dangerous levels, the patient begins to lose weight, and a splenic infarction occurs. The person is in a very serious condition, and a blast crisis is gradually developing. Chronic myeloid leukemia (CML) causes the development of bone marrow fibrosis; the life expectancy of a person in this condition is quite short and depends on supportive therapy.

Note! Associated symptoms at different stages of pathology development are enlarged lymph nodes, the development of anemia, disturbances in the functioning of the central nervous system, thrombocytopenia, etc.

Diagnostics

CML, like other myeloid leukemia, is diagnosed by an oncologist. First, the patient takes a blood test, where an increase in the number of white cells that have not yet matured can be detected; attention is paid to the increased number of red blood cells and platelets. This analysis also makes it possible to determine abnormalities in the functioning of the spleen and liver. Based on the results of the analysis, a preliminary diagnosis can be made and the phase of the disease can be determined.

The doctor then orders a bone marrow biopsy, which is taken from the head of the femur or sternum. Together with the biopsy, bone marrow aspiration is performed, as a result of which the pathological chromosome can be detected. For the same purpose, PCR is used, as a result of which an abnormal gene is detected in the red bone marrow.

Cytochemical diagnostics are often carried out, which makes it possible to identify a pathological process in the body, but also to differentiate the disease from other types of blood oncology. Cytogenetic diagnostics are also used, in which the patient’s chromosomes and genes are studied.

Instrumental research methods include ultrasound, MRI and CT, which make it possible to identify metastases, as well as the condition of organs, tissues and the brain.

Treatment of blood oncology

At the initial stage of development of the disease, drug treatment is used. Doctors often prescribe A-interferon and Myelosan. Relief occurs in the sixth week of taking the drugs. Then maintenance therapy is carried out; in case of exacerbation of the disease, courses of treatment with Myelosan are carried out. If this drug is ineffective, use Myelobromol for three weeks. As a last resort, the doctor prescribes Dopan or Hexaphosphamide.

Also, to treat pathology, chemotherapy is used using chemicals that reduce the growth of tumor cells and promote their destruction. This method is used at different stages of the disease. It has side effects, which are expressed in disruption of the gastrointestinal tract, the appearance of allergic reactions, muscle pain, and cramps. After a course of chemotherapy, the doctor prescribes Interferon to restore the immune system.

If chemotherapy is ineffective, resort to. It can also be used to prepare a patient for a bone marrow transplant.

Note! In some cases, the spleen is removed due to severe pain in the abdominal area, significant enlargement of the organ, or the threat of rupture.

In order to prevent the development of microscopic thrombosis and swelling of the retina, doctors prescribe leukocytophoresis. In this case, the blood is purified from pathological cells.

Bone marrow transplantation

This procedure significantly increases the patient’s likelihood of recovery. The patient's relatives often act as donors. After conducting various compatibility tests, the patient begins to prepare for surgery for about one week. During this period of time, he undergoes radiation and chemotherapy.

During the operation, donor stem cells enter the patient's bloodstream, accumulate in the bone marrow and begin to function there within one month. During this period of time, the patient’s immunity is reduced, so he is prescribed medications to reduce the risk of rejection of donor cells. The doctor also prescribes antibacterial and antifungal medications. Gradually, the patient’s well-being improves, bones and soft tissues, blood are cleared of pathological cells and begin to function normally. Full recovery occurs after a few months, during which time the patient is under the supervision of the attending physician.

Note! Complete recovery is only possible with a stem cell transplant. In this case, they must be completely the same for the patient and the donor.

Prognosis and prevention

If the chronic stage of the disease is diagnosed and a bone marrow transplant is performed in a timely manner, a complete recovery of the patient is possible. Most people die when they have an acceleration phase or blast crisis. In 10% of them, death occurs within two years of diagnosis. With the terminal stage of the disease, a person can live for another six months, but if the treatment gives positive results and remission begins, then life expectancy increases to one year.

Methods for the prevention of CML in modern medicine have not been developed, since the exact causes of the development of the pathology have not yet been clarified. Doctors recommend leading a healthy lifestyle, not abusing medications when treating various diseases, and also avoiding exposure to radiation.