Myelogenous leukemia symptoms. Chronic myeloid leukemia

– 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 with an asymptomatic course of the 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.

Chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a slowly progressive type of leukemia characterized by the uncontrolled formation of myeloid cells in the bone marrow and the release of immature cells into the peripheral blood.

The cells produced by leukemia are abnormal, immature forms. The lifespan of these immature cells is longer than that of mature leukocytes. As the disease progresses, immature cells accumulate in the bone marrow, crowding out normal hematopoietic cells.

Causes of CML

CML is almost always caused by a mutation in a gene on a chromosome called the Philadelphia chromosome. This mutation occurs gradually throughout life. It is not transmitted from parents to children. In most cases, the cause of the mutation is unknown. Research shows that the development of CML is influenced by exposure to large doses of radiation, for example, after nuclear accidents or atomic explosions. However, most CML patients have not been exposed to radiation.

Symptoms of CML

The above symptoms, in addition to chronic myeloid leukemia, can be caused by other, less serious diseases. If you experience any of these, seek medical advice.

Weakness

Lack of energy

Fatigue

Unexplained weight loss

Night sweats

Fever

Pain or fullness below the ribs

Bone pain

Joint pain

Decreased exercise tolerance

Enlarged liver or spleen

Unreasonable bleeding or bruising.

Diagnosis of CML

The doctor will ask about your symptoms and medical history and perform a physical examination. The doctor may also check for swelling in the liver, spleen, or lymph nodes in the armpits, groin, or neck. You may be referred to an oncologist, a doctor who specializes in treating cancer.

Tests may include:

Blood tests - to check for changes in the number or appearance of different types of blood cells

Bone marrow aspiration - removal of a sample of bone marrow fluid to test for cancer cells

Bone marrow biopsy - removal of a sample of bone marrow fluid and a small sample of bone to check for cancer cells

Examining samples under a microscope - examining samples of blood, bone marrow fluid, lymph node tissue, or cerebrospinal fluid

Tests of bones, blood, bone marrow, lymph node tissue, or cerebrospinal fluid - to classify the type of leukemia and determine whether there are leukemia cells in the lymph nodes or cerebrospinal fluid

Cytogenetic analysis is a test that allows you to find certain changes in the chromosomes (genetic material) of lymphocytes. Used to establish a specific diagnosis and develop a treatment plan for CML

Chest X-ray - detects signs of lung infection or breast cancer

Abdominal CT scan - a type of x-ray that uses a computer to take pictures of organs inside the body

MRI is a test that uses magnetic waves to take pictures of structures inside the body

Ultrasound is a test that uses sound waves to study internal organs.

Treatment of CML

The treatment method for CML depends on the stage of the disease and the patient’s health status.

Drug therapy for chronic myeloid leukemia

Drugs have been developed that can suppress molecules that trigger the development of leukemia and the gene associated with it. These drugs are often used in the early stages of CML. They are a better treatment option than chemotherapy and biological therapy. The following medications are used to treat chronic myeloid leukemia:

Imatinib (Gleevec, Genfatinib, Filachromin, Neopax, Imatinib, etc.)

Dasatinib (Sprycel)

Nilotinib (Tasigna).

Bosutinib (Bosutinibum).

Chemotherapy for chronic myeloid leukemia

Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy drugs can be given in various forms: tablets, injections, or catheter administration. The drugs enter the bloodstream and travel throughout the body, killing mainly cancer cells, but also some healthy cells.

Biological therapy

This treatment for CML is still being tested in clinical settings. Treatment involves the use of drugs or substances that are used to increase or restore the body's natural defenses against cancer. This type of therapy is also called biological response modifier therapy. Sometimes very specific (monoclonal) antibodies are used that are designed to suppress leukemia cells. Currently, monoclonal antibody therapy is limited to clinical trials and is not available in Russia.

Chemotherapy with stem cell transplantation

Chemotherapy with stem cell transplantation for the treatment of CML is still in clinical trials. Chemotherapy is accompanied by stem cell transplantation (immature blood cells). They will replace the blood-forming cells destroyed by cancer treatment. Stem cells are selected from the blood or bone marrow of a donor and then injected into the patient's body.

Lymphocyte infusion

Lymphocytes are a type of white blood cell. Lymphocytes from a donor are introduced into the patient's body and cancer cells do not attack them.

Surgery for chronic myeloid leukemia

A splenectomy, an operation to remove the spleen, may be performed. It is performed if the spleen is enlarged or other complications arise.

TRANSPLANTATION

Bone marrow transplantation

Because chemotherapy drugs destroy bone marrow cells, a transplant is a truly life-saving treatment for the patient. The goal of a bone marrow transplant is to introduce healthy bone marrow cells into the body while being treated with high doses of chemotherapy drugs (thereby increasing the likelihood of destroying cancer cells and making a full recovery).

Stem cell transplant

Stem cells are cells in the early stages of development that have not yet turned into leukocytes, erythrocytes or platelets. Today, stem cells are obtained from peripheral blood using a special device that allows sorting different types of cells. In such a device, the blood is centrifuged at high speed and separated into its component elements. The process lasts 3-4 hours.

Stem cells are selected and frozen until the transplant procedure. If the transplantation is successful, the stem cells will take root in the recipient’s body, undergo a maturation process, and subsequently form all types of blood cells: leukocytes, erythrocytes and platelets. Transplantation of cells from a donor is called allogeneic transplantation; transplantation of the patient's own cells (usually stem cells) is called autologous transplantation.

Allogeneic transplantation (from a compatible donor)

In allogeneic transplantation, the source of bone marrow cells or stem cells is a donor whose cells have been found suitable for transplantation after a tissue compatibility test. In some cases, the donor may be a relative of the patient, but in principle cells from a stranger can be used if they have successfully passed the compatibility test.

Before the transplant procedure, it is necessary to completely destroy all malignant cells in the patient's bone marrow. For this purpose, cytotoxic drugs are prescribed in high doses and radiotherapy (irradiation of the whole body). The graft is then introduced into the patient's body through an intravenous infusion.

The process of engraftment of transplanted cells takes several weeks. All this time, the patient’s immune system functions at an extremely low level, so during this period the patient must be carefully protected from infections. For this reason, after the transplant procedure, the patient is kept in isolation until his blood test shows an increase in the number of white blood cells. This growth is a symptom of the restoration of the immune system, the engraftment of the transplant and the resumption of the hematopoietic process.

It is important to remain under medical supervision for several months after the transplant procedure to ensure that a condition called graft-versus-host disease is recognized early if necessary. This is a condition in which cells from the transplanted bone marrow attack the patient's body tissue. It may occur within 6 months after the transplant procedure. Graft-versus-host disease can be accompanied by symptoms of varying severity - from mild (diarrhea, rash) to severe (liver failure). Appropriate medications are prescribed to treat this condition. The occurrence of graft-versus-host disease does not mean that the transplant was unsuccessful.

Autologous transplantation

In this procedure, the stem cell donor is the patient himself, who is in remission.

Blood is drawn from a vein in one arm of the patient, passed through a machine that separates the stem cells, and returned to the body through a vein in the other arm.

What is relapse in CML?

The word relapse is used if there was a remission. In relation to CML, remission can be, firstly, hematological, that is, when all external manifestations of the disease disappear (normalization of the size of the liver and spleen, disappearance of lesions in organs), as well as complete normalization of peripheral blood parameters; secondly, cytogenetic, when cells with the Philadelphia chromosome (Ph) are no longer detected; and the third option, molecular, when the most sensitive molecular genetic methods (polymerase chain reaction, PCR) cannot detect the product (transcript) of the pathological BCR-ABL gene. The existence of molecular remission is controversial, since the ability to detect a gene transcript depends on the sensitivity of the gene used, the quality of the reagent, and the experience of the laboratory staff. In addition, the sensitivity of current techniques is generally limited. Today, even in the best laboratories in the world, a pathological transcript is detected if its amount is greater than 1 per 100,000 transcript of a normal control gene. In connection with this, the word molecular remission in the scientific literature has been replaced by the term “PCR negativity.”

Since there are different levels of remission, there are also different levels of relapse - hematological (the appearance of damage to various organs, again deterioration of clinical blood test parameters), cytogenetic (the appearance of Ph-positive cells), molecular (renewed detection of the BCR-ABL transcript).

Abnormal Pb'-chromosome in a cell of a CML patient

How can “relapse of CML” be detected?

Today, regardless of the depth of remission achieved, even molecular, constant continuous therapy with tyrosine kinase inhibitors (TKIs) is recommended. Interruptions in therapy or discontinuation of drugs are indicated only due to complications associated specifically with TKIs. Naturally, drugs are also discontinued if there was no initial effect or the achieved effect was later lost.

During therapy, it is extremely important to monitor the level of leukemic cells using not just a clinical blood test, but also cytogenetic (especially during the first year of treatment) and PCR studies. It is molecular genetic techniques that detect the first signs of relapse of the disease (the appearance of leukemic cells) and indicate an unfavorable situation.

Why does relapse occur?

There are many reasons and not all of them have been studied. I will list only the most striking or studied:

Oddly enough, a frequent cause of relapse is inadequate use of the drug by patients. Unfortunately, we have to face a situation where the patient voluntarily reduces the dose of the drug, stops taking it altogether, or takes it from time to time.

Simultaneous long-term use of drugs or substances that reduce the concentration of TKIs. It is known that these drugs are destroyed in the liver under the influence of certain enzymes - cytochromes. There is a large group of drugs or substances that significantly increase the activity of these cytochromes. In such a situation, TKIs can disintegrate quickly, their concentration is sharply reduced and, consequently, their effectiveness is reduced. Therefore, we always warn patients about the advisability of informing us about all medications they are taking. We do not recommend taking dietary supplements due to the impossibility of assessing their effect on TKI concentrations. Known drugs that significantly activate cytochromes and reduce the activity of TKIs include, for example, St. John's wort.

The effectiveness of TKIs can also be reduced due to a lack of proteins that “pump” drugs into the cell or, conversely, an excess of proteins that “pump” them out of the cell. This may lead to a decrease in intracellular TKI concentrations.

The most studied cause of relapses should be considered the appearance of mutations (changes) in the BCR-ABL gene. There are more than 90 types of mutations that can change the structure of the BCR-ABL protein. Not all of them lead to disruption of the structure of the protein region where all TKIs are attached. Therefore, not all mutations have an equally bad effect on treatment outcomes. In addition, different drugs have their own group of “bad” mutations. At the same time, there is one mutation, the appearance of which leads to the ineffectiveness of all 3 drugs (imatinib, nilotinib, dasatinib) registered in Russia. Only a TKI called ponatinib (registered in the USA at the end of 2012) is able to overcome the changes that this mutation brings to the cell. It is extremely important to perform mutation analysis as soon as the first signs of ineffectiveness of a particular TKI appear. The results of this analysis greatly help the hematologist select the “right” TKI for a particular patient.

Is it possible to prevent relapse?

Of course, it is possible if the cause is improper use of the drug. Although it is not always possible to correct the situation subsequently, in some patients the resumption of adequate therapy leads to an improved response.

The risk of relapse may also be reduced if the patient is not taking medications that affect TKI concentrations.

Timely initiation of TKI therapy immediately after diagnosis is critical. In addition, in case of ineffectiveness of the first line of TKI, rapid replacement with another TKI is very important. All this contributes to a rapid decrease in the number and activity of leukemia cells. This reduces the risk of developing additional genetic changes (mutations, etc.), which most often lead to relapses of the disease even after long-term remission.

Considering all of the above, along with compliance with all the rules for taking the drug, timely examination to assess the depth of remission is extremely important. It is careful monitoring (cytogenetic and/or PCR analysis) that will allow the doctor to detect a relapse of the disease in the early stages and will make it possible to timely prescribe more effective therapy to achieve remission again.

Chronic myeloid leukemia in questions and answers

I got sick with hml. What to do?

CML is chronic myeloid leukemia, an oncohematological blood disease, one of the types of existing leukemias.

Chronic myeloid leukemia is a blood tumor that does not limit the life expectancy of the vast majority of patients, thanks to modern drugs and a responsible attitude to treatment.

What to do? Trust your treating hematologist and follow all recommendations, as well as conduct diagnostic tests in a timely manner.

How long will I live?

Until recently, the average life expectancy for patients with CML was 3.5 years. Modern medicines make it possible to extend it for a period of more than 20 years, while the quality of life of patients remains at a high level and practically does not differ from the life of a healthy person.

Is CML contagious and is it inherited?

CML is not a contagious disease and is not inherited.

Could CML be related to my job or the environment?

The influence on the incidence of CML of such factors as work in hazardous industries, low doses of radiation, weak electromagnetic radiation, poor ecology of megacities, etc., has not been confirmed. Therefore, do not look for the cause, accept the disease and learn to live with it.

Why do you need to take medicine every day?

The medicine must be taken continuously, for life, without breaks, because a certain concentration of the drug must be maintained in the blood. Self-discontinuation of the drug may cause progression of the disease or the drug will no longer act on the body.

When is the best time to take imatinib?

You can take Imatinib at a time that is convenient for you.

The last dose of Imatinib should be no later than 2 hours before bedtime.

Why should you not take breaks from taking your medication when breaks are necessary?

Self-discontinuation of the drug may cause the loss of all achieved results and lead to progression of the disease (relapse). Breaks in taking the drug are possible only if there are medical indications, and this issue can only be resolved by a hematologist.

Is it possible to treat with herbs?

Taking herbs and dietary supplements is not recommended due to the inability to assess their effect on the concentration of the drug in the blood. Known agents that significantly reduce the activity of the drug include, for example, St. John's wort and ginseng.

I heard that oncology and CML can be cured with chaga mushroom or kerosene?

Unfortunately, it is impossible to cure oncology and CML with folk remedies.

Why is it necessary to get tested so often?

Tests are necessary to monitor the course of the disease and timely adjustment of treatment. To avoid repeated deterioration in your health, each examination must be carried out in a timely manner, when prescribed by the doctor, and the success of your treatment depends on this.

Why is a general blood test not enough?

A complete blood count is a blood sample taken from a finger or vein. Includes counting of white blood cells, red blood cells, platelets and other blood components, but this analysis is not enough to see the full picture of the course of your disease.

What is cytogenetics? Is it necessary to take it?

Cytogenetic analysis is the collection of bone marrow during sternal puncture from the sternum. This study determines chromosomal changes and response to treatment, % of cells with the Philadelphia chromosome. The frequency of studies is determined by the attending physician.

What is “molecular” diagnostics?

To conduct this study, blood is donated from a vein.

Molecular analysis is the most sensitive method available for diagnosing CML.

Is there any special diet for CML?

No special diet is required for CML.

What foods should you not eat if you have CML?

Can I take vitamins?

It is necessary to be extremely careful with the use of vitamins in case of CML. Be sure to consult with your doctor.

Is it possible to drink alcohol?

Drinking alcohol is not recommended, because... it can speed up the absorption of drugs from the digestive tract, creating higher concentrations of the drug in the body than would normally be the case. This leads to an overdose or the development of toxic reactions that have a detrimental effect on the liver, like alcohol itself.

Can I work?

In general, CML does not affect your ability to work, but you need to be mindful of adherence to your treatment regimen.

Can I play sports?

Consult your healthcare provider.

Is it possible to go to the bathhouse?

Is it possible to relax at sea?

You can and should relax, subject to simple rules:

Closed clothing and hat;

Using an umbrella (awning);

Don't overheat.

However,

Is it possible to sunbathe?

Exposure to the sun before 11 am and after 5 pm using sunscreen is not contraindicated.

I have a strong side effect. What to do?

Treatment of CML is often accompanied by side effects, which depend on the dose of the drug, the phase of CML, duration of treatment, gender, and age. Different people's reactions to medications vary, so your side effects may differ from other patients. If side effects occur, do not stop taking the drug, consult your doctor immediately, as some side effects require treatment.

Nausea

Try to select or exclude certain foods while taking the medication. For example, you can eat a green apple. Eliminate dairy, sour and smoked products.

Heartburn

Limit overeating, spicy seasonings, caffeine and alcohol.

Do not go to bed for 1-2 hours after taking imatinib.

Fluid retention with the development of edema

Limit salt intake in the diet, reduce the amount of fluid consumed (especially at night).

Cosmetic procedures.

Consultation with your attending physician is required.

Diarrhea (diarrhea)

Try to exclude foods such as prunes, beets, dairy, etc.

Consultation with your attending physician is required.

Dried apricots, beans, legumes, cereals, meat, seaweed, fresh champignons, potatoes (especially baked or boiled in their jackets), carrots, beets, pumpkin, radishes, peppers, tomatoes, cucumbers, cabbage, herbs (especially spinach and parsley);

Apples, bananas, watermelons, melons, kiwis, mangoes, avocados, cherries, grapes, blackcurrants, gooseberries, blackberries, dried fruits (figs, dried apricots, prunes, dates), nuts (especially walnuts and hazelnuts).

Cashews, buckwheat, buckwheat, millet, bran, legumes (especially white beans and soybeans), carrots, potatoes, spinach and other leafy vegetables apricots, peaches, bananas, blackberries, raspberries, strawberries, sesame seeds, nuts.

Skin rashes

Consultation with your attending physician is necessary.

Increased temperature, fever

Such a reaction is possible due to the effect of the drug.

Consultation with your attending physician is necessary.

I got sick (cold, flu, etc.). What to do?

Do not self-medicate, consult your doctor.

I am prescribed medications for a concomitant disease, can they be taken together with imatinib?

Consult with specialists.

If complaints arise during treatment, you should contact your doctor to decide whether it is necessary to adjust the therapy.

Do I need a disability to receive medications?

Disability is not required to receive medications to treat CML.

Cancer patients are provided with all medications free of charge based on current legislation.

In each case, registration of disability is an individual issue and you yourself need to determine for yourself whether a disability is needed or not. Whether a person is granted disability or not will depend on medical indications.

Is there a disability group for CML?

Yes, they do. To receive a disability group, there must be medical and social indications.

Criteria for ITU: The disease has an unfavorable prognosis. The appearance of signs of acceleration, the development of blast crisis, indicating severe dysfunction and a poor prognosis.

Disability criteria.

Disability group III is determined by patients who have been diagnosed with a chronic phase, upon achieving clinical and hematological remission, an adequate reduction in leukocytosis, in the presence of a limitation of the ability to work, stage I, which requires rational employment in conditions and types of work that are not contraindicated or a reduction in the amount of work performed. .

Disability group II is determined by patients with disease progression, in the absence of complete clinical and hematological remission and an adequate reduction in leukocytosis; development of complications, limitation of the ability to self-care, movement and work activity II degree.

Disability group I is determined by the patient in the presence of a blast crisis, an acceleration phase, severe purulent-septic complications, and a limitation of the ability to self-care and movement of the III degree. Patients need constant outside help.

We want a baby

Planning pregnancy is not an easy issue for healthy people, but for patients with CML this issue requires a responsible decision. But in any case, this decision should be made only with the participation of the attending physician, because will require treatment adjustments.

Today, patients with CML give birth to healthy children in almost all regions of the country.

What are 2nd line drugs?

There are currently a number of medications available for patients who do not respond to Imatinib. They are much stronger in their effect, but selection for each patient is carried out individually.

How does imatinib interact with other drugs?

When prescribing treatment for concomitant diseases by other specialists, a conclusion from your hematologist is required.

Please note:

CYP3A4/5 inducers - drugs that reduce the concentration of TKIs in plasma:

Glucocorticoids, griseofulvin, dexamethasone, diphenin, carbamazepine, oxcarbazepine, progesterone, rifabutin, rifampicin, sulfadimizine, troglitazone, phenylbutazone, phenobarbital, ethosuximide.

CYP3A4/5 inhibitors - drugs that increase plasma concentrations of TKIs:

Azithromycin, amiodarone, anastrozole, verapamil, gestodene, grapefruit juice, danazol, dexamethasone, diltiazem, dirithromycin, disulfiram, zafirlukast, isoniazid, itraconazole, metronidazole, mibefradil, miconazole (moderate), norfloxacin, oxyconazole, omeprazole (weak ), paroxetine (weak ), sertindole, sertraline, fluvoxamine, fluoxetine, quinidine, quinine, cyclosporine, ketoconazole, cimetidine, clarithromycin, erythromycin, clotrimazole, ethinyl estradiol

Drugs that prolong the QT interval

- Antiarrhythmic: adenosine, amiodarone, flecainide, quinidine, sotalol.

- Anticonvulsants: felbamate, phenytoin.

- Antidepressants: amitriptyline, citalopram, desipramine, doxepin, imipramine, paroxetine, sertraline.

- Antihistamines: astemizole, diphenhydramine, loratadine, terfenadine.

- Antihypertensive: indapamide, mibefradil, hydrochlorothiazide, nifedipine.

- Antimicrobial: macrolides, fluoroquinolones.

- Antitumor: arsenic trioxide, tamoxifen.

- Neuroleptics: chlorpromazine, clozapine, droperidol, haloperidol, risperidone.

- Drugs acting on the gastrointestinal tract: cisapride, dolasetron, octreotide.

- Drugs of different groups: amantadine, methadone, salmeterol, sumatriptan, tacrolimus.

Myeloid leukemia is a disease that is directly related to oncology and involves damage to blood cells. Myeloid leukemia affects bone marrow stem cells. The ICD-10 code for the disease is C92. The pathology spreads rapidly, so after some time the affected elements stop performing their functions. It can last for a long time without showing symptoms. According to statistics, it is detected more often in people over 30 years of age.

Like all cancers, atypical leukemia has not been studied. Now researchers and doctors are speculating about the possible causes of the pathology:

A common theory is the effect of chemicals on humans;
bacterial diseases;
long-term exposure to arenes;
side effects from tumor treatment;
the result of another cancer.

Scientists are actively uncovering possible pathways of the disease in order to subsequently study and eradicate the disorder.

Risk factors

A number of circumstances can significantly influence the occurrence of oncology, namely:

exposure to radiation;
age.

Two thirds of the factors cannot be changed, but trying to avoid the first is quite feasible.

Kinds

Medical professionals distinguish two types of myeloid leukemia.

Spicy

In an acute form of oncology, cell infection occurs that cannot be controlled. In a short time, the healthy cell is replaced by the damaged one. Timely treatment will help prolong a person's life. Its absence limits a person’s existence to up to 2 months.

The first symptom of acute myeloid leukemia may not cause alarm, but you should consult a doctor for a verdict. Oncological symptoms of myeloid leukemia appear simultaneously or increase gradually.

Acute myeloblastic syndrome and symptoms:

pain in bones and joints;
nasal hemorrhages;
increased sweat production during sleep;
disruptions in bleeding, which causes pale skin;
frequent infections;
inflammation of the gums;
the appearance of hematomas over the body area;
breathing problems even with low levels of physical activity.

The manifestation of two or more symptoms indicates serious problems in the body; it is recommended to visit a clinic. Prescribing timely treatment will help save life.

Acute myeloid leukemia reveals a classification that includes a lot of factors and causes, separated into groups:

primitive changes in genes;
changes due to impaired development of tissues and organs;
consequence of other diseases;
Down syndrome;
myeloid sarcoma;
Treatment, diagnosis, symptoms and signs may vary.

Chronic lymphocytic leukemia

In this case, scientists have established a connection that determines the cause of the disease and the disorder in the human genetic component. Lymphocytic leukemia only affects stem cells that can divide indefinitely. Mutations occur in new cells, since due to incomplete formation it is easier to penetrate into them. A healthy blood cell gradually transforms into a white blood cell. They then accumulate in the bone marrow and from there circulate throughout the body, slowly infecting human organs. Chronic myeloid leukemia (CML) can develop into acute lymphoblastic leukemia.

Stages of chronic myeloid leukemia:

First stage. The disease increases gradually. It is characterized by an enlarged spleen, secondary signs of myeloid leukemia: the level of granular leukocytes, as well as non-nuclear elements in the peripheral blood increases. The symptoms of the first stage of chronic myeloid leukemia can be compared with the symptoms of acute myeloid leukemia: shortness of breath, heaviness in the stomach, sweating. Serious sensations indicating increased oncology:

pain under the ribs, flowing into back pain;
exhaustion of the body.

Against this background, a splenic infarction may develop, and then problems with the liver will appear.

The second stage of chronic oncology is characterized by the accelerated development of a living malignant tumor. The initial stage of the disease is not shown or is expressed to an extremely small extent. This condition is characterized by:

increased body temperature;
anemia;
fast fatiguability;
the number of white blood cells also continues to increase;
In addition to leukocytes, other blood cells also increase.

Prognostic results and prompt completion of the necessary procedures lead to the discovery of components in the blood that should not be present during the normal development of the body. The degree of immature leukocytes increases. This affects the periodic itching of the skin.

The third (final) stage is characterized by pathofunctional changes, in which oxygen starvation of every part of human tissue occurs, as well as a violation of internal metabolism. Brain cells suffer more from oxygen starvation. The most serious manifestations of the terminal stage:

joint pain;
fatigue;
temperature rise up to 40 degrees;
the patient's weight decreases sharply;
splenic infarction;
positive pH.

Additional symptoms include problems with nerve endings and changes in the internal composition of the blood. Life expectancy at this stage of the disease depends on the drugs and therapy used.

Diagnostics

Modern methods are succeeding in computing cancer diseases. Common, standard processes that make it possible to identify a malignant element of a blood cell in a person:

Conducted by the UAC. Thanks to this procedure, the extent of the total number of cells is established. What does this give? In patients suffering from myeloid leukemia, the number of immature cells increases, and a decrease in the number of red blood cells and platelets is recorded.
A biochemical blood test can detect disruptions in the functioning of the liver and spleen. Such problems are caused by the penetration of leukemia cells into organs.
Collection of tissues and cells, as well as penetration of foreign bodies into the bone marrow. These two procedures are carried out at the same time. Brain prototypes are taken from the femur.
A method of studying genetics and human development through the study of chromosomes. The structure of human genes with cancer contains leukemia cells, and it is they that make it possible to detect acute myeloid leukemia.
Mixing of different orbitals of an atom in a molecule. This method is used to study chromosomes; in cases of cancer, the abnormal chromosomes are found.
A myelogram shows bone marrow statistics in tabular form.
The hemogram allows you to examine the patient and accurately establish the diagnosis. It is characterized by rapid distribution of components and an extensive method of establishing localization.

Standard diagnostic methods are also used: MRI, ultrasound, etc. They cannot promise the patient an accurate diagnosis or stage.

Treatment

Since there are differences between the symptoms of chronic and acute diseases, therefore, the treatment provided is different.

Treatment of chronic myeloid leukemia

The phases separate the degree of damage to the human body, so treatment is provided depending on the stage of the disease. In the chronic or inactive stage, it is recommended to follow general treatment standards, lead a healthy lifestyle, and eat a diet rich in vitamins. Rest at this stage is compared to work, the amount of vitamins is also prescribed.

If the level of leukocytes continues to increase, complications are noticed, patients are prescribed cytostatic medications. After completing a course of treatment with the drug, therapy is maintained, which is aimed at restoring the proper functioning of the spleen. Radiotherapy is used when the spleen has not returned to its original shape. After which the course of treatment is interrupted for 31 days, then repeated with restorative therapy.

The phase of oxygen starvation most often involves one, less often two, chemical preparations. More often they are specialized preparations that contain certain groups of vitamins that help maintain health and life in humans. The principle of use is the same as in the inactive phase: first, effective therapy is carried out, and then maintenance use. Courses of intravenous administration of chemical drugs are carried out three times a year. If the technique does not work, a procedure is carried out to separate the blood into plasma and other components. For symptoms of CML, donor blood transfusions are used, which directly contain cells, plasma, as well as admixtures of red blood cells and platelets. Radiotherapy is administered for significant amounts of malignant tumor.

70% of those suffering from myeloid leukemia received a guarantee of recovery through a bone marrow transplant. This procedure is carried out at the initial stage of ailments. And it may be a consequence of removal of the spleen. This organ can be “removed” in two ways: the unplanned one involves rupture of the spleen, and the main one depends on a number of factors. The bone marrow for transplantation must be identical to the patient's brain.

Treatment of acute myeloid leukemia

What clinical guidelines are being followed? At the induction stage of treatment, a set of measures is carried out aimed at eliminating the causes and symptoms of the disease and removing unnecessary leukemia cells. Consolidation measures eliminate the possibility of relapse and maintain a person’s normal condition. Classification affects the principle of treatment of AML, age, gender, individual tolerance and capabilities.

The technique of intravenous administration of a cytostatic drug has become widespread. The process continues for a week. The first three days are combined with another medication from the antibiotic group.

When there is a risk of developing physical or infectious diseases, a less intensive procedure is used, the essence of which is to create a set of measures for the patient. This includes surgical intervention, psychotherapeutic assistance to the patient, etc.

Induction measures give positive results in more than 50% of patients. The absence of the second degree of consolidation leads to relapse, and is therefore considered a necessary measure. If the cancer returns after the standard 3-5 maintenance chemotherapy procedures, a bone marrow transplant is performed. Hematopoiesis helps restore the body. Peripheral blood is required for the test. In Israel, recovery rates from lymphocytic leukemia are high due to the fact that unfavorable conditions for a person are eliminated immediately and the tumor process subsides. The method of detecting blasts in peripheral blood is also used there.

Blast crisis is a malignant process that is considered final. At this stage, the syndromes cannot be cured, only supporting vital processes, since the etiology and pathogenesis of the phase are not fully understood. Negative experience indicates that leukocytes exceed the required volume.

Prognosis of acute myeloid leukemia

Oncologists give different estimates of survival for AML, as it is determined by a number of factors, for example, age, gender and others. A consistent evaluation of AML classifications has shown that median survival varies from 15 to 65%. The prognosis for the return of the disease is from 30 to 80%.

The presence of physical and infectious disorders causes a worse prognosis for older people. The presence of parallel ailments makes chemotherapy, so necessary for the treatment of myeloid leukemia, unavailable. With hematological diseases, the picture looks much more disappointing than with the occurrence of a malignant tumor as a result of a concomitant disease. Acute myeloid leukemia is rarely observed in children, more often in adults.

Prognosis of chronic myeloid leukemia

The determining reason for a positive result is the moment of treatment. The following factors depend on the duration and likelihood of curing cancer: the size of the expansion of the liver, spleen, the number of nuclear-free blood elements, white blood cells, immature bone marrow cells.

The possibility of death increases along with the number of signs that determine the development of oncology. Concomitant infections or subcutaneous hemorrhages of body parts are a common cause of death. The average life expectancy is two years. Prompt identification and treatment of the disease can multiply this period tenfold.

Chronic myeloid leukemia is an oncological blood disease, which is characterized by a decrease in the level of leukocytes and the appearance of a large number of immature cells - granulocytes.

According to statistics, the incidence of myeloid leukemia is the same in women and men, most often occurring at the age of 30-40 years.

Causes of chronic myeloid leukemia

Among the main factors that provoke blood cancer are:

Hereditary predisposition - cases of blood cancer are recorded in relatives
Genetic predisposition - the presence of congenital chromosomal mutations, for example, Down syndrome, increases the likelihood of developing the disease
Exposure to radiation
The use of chemotherapy and radiation therapy in the treatment of other cancers can provoke myeloid leukemia

Stages of chronic myeloid leukemia

The development of chronic myeloid leukemia occurs in three successive stages:

Chronic stage

The longest stage, which usually lasts 3-4 years. Most often it occurs asymptomatically or with a vague clinical picture, which does not raise suspicions about the tumor nature of the disease either among doctors or patients. Chronic myeloid leukemia is usually discovered through a random blood test.

Acceleration stage

At this stage, the disease is activated, the level of pathological blood cells increases at a rapid pace. The duration of acceleration is about a year.

At this stage, with proper therapy, there is a chance to return leukemia to the chronic stage.

Terminal stage

The most acute stage lasts no more than 6 months and ends in death. At this stage, blood cells are almost completely replaced by pathological granulocytes.

Symptoms of chronic myeloid leukemia

Manifestations of the disease directly depend on the stage.

Symptoms of the chronic stage:

In most cases it is asymptomatic. Some patients complain of weakness and increased fatigue, but, as a rule, they do not attach any importance to this. At this stage, the disease is detected during the next blood test.

In some cases, weight loss, loss of appetite, and increased sweating may occur, especially during night sleep.

With an enlarged spleen, pain may occur in the left half of the abdomen, especially after eating.

In rare cases, bleeding tends to develop due to decreased platelet levels. Or, on the contrary, when they increase, blood clots form, which is fraught with myocardial infarction, stroke, visual and breathing problems, and headaches.

Symptoms of the accelerated stage:

As a rule, it is at this stage that the first manifestations of the disease are felt. Patients complain of poor health, severe weakness, increased sweating and pain in joints and bones. Worries include increased body temperature, increased bleeding and an enlarged abdomen due to the growth of tumor tissue in the spleen.

Diagnosis of chronic myeloid leukemia

Diagnosis of chronic myeloid leukemia is carried out by an oncologist-hematologist.

Blood tests

The main diagnostic method. Using it you can not only make a diagnosis, but also determine the stage of the pathological process.

At the chronic stage, a general blood test shows an increase in platelets and the appearance of granulocytes against the background of a decrease in the total number of leukocytes.

At the accelerated stage, granulocytes already account for 10-19% of leukocytes; the platelet content can be either increased or, conversely, decreased.

During the terminal stage, the granulocyte count steadily increases, and the platelet level decreases.

A biochemical blood test is performed to analyze the functioning of the liver and spleen, which usually suffer from myeloid leukemia.

Bone marrow biopsy

For this study, bone marrow is collected with a thin needle, after which the material is sent to the laboratory for detailed analysis.

Most often, bone marrow is taken from the head of the femur, however, the calcaneus, sternum, and wings of the pelvic bones can be used.

In the bone marrow, a picture similar to a blood test is observed - the number of immature leukocytes increases.

Hybridization and PCR

A study such as hybridization is necessary in order to identify an abnormal chromosome, and PCR is necessary to identify an abnormal gene.

Cytochemical study

The essence of the study is that when special dyes are added to blood samples, certain reactions are observed. Using them, the doctor can not only determine the presence of a pathological process, but also make a differential diagnosis between chronic myeloid leukemia and other types of blood cancer.

In a cytochemical study, a decrease in alkaline phosphatase is observed in chronic myeloid leukemia.

Cytogenetic studies

This study is based on the study of the patient's genes and chromosomes. To do this, blood is drawn from a vein and sent for a special analysis. The result, as a rule, is ready only after a month.

In chronic myeloid leukemia, the so-called Philadelphia chromosome is detected - the culprit in the development of the disease.

Instrumental research methods

Ultrasound, computed tomography and magnetic resonance imaging are necessary to diagnose metastases, the condition of the brain and internal organs.

Treatment of chronic myeloid leukemia

Bone marrow transplantation offers a real chance of recovery for patients with chronic myeloid leukemia.

This treatment option consists of several successive stages.

Search for a bone marrow donor. The most suitable donors for transplantation are close relatives. If a suitable candidate is not found among them, it is necessary to look for such a person in special donor banks.

Once found, various compatibility tests are carried out to ensure that the donor material will not be accepted aggressively by the patient's body.

Preparing the patient for surgery lasts 1-1.5 weeks. At this time, the patient undergoes chemotherapy and radiation therapy.

Bone marrow transplantation.

During the procedure, a catheter is inserted into the patient's vein, through which stem cells enter the bloodstream. They settle in the bone marrow and after a while begin to work there. To prevent the main complication - rejection - medications are prescribed that are designed to suppress the immune system and prevent inflammation.

Decreased immunity. From the moment of introduction of stem cells to the start of their work in the patient’s body, as a rule, about a month passes. At this time, under the influence of special drugs, the patient’s immunity is reduced, this is necessary to prevent rejection. However, on the other hand, this creates a high risk of infection. The patient must spend this period in a hospital, in a special ward - he is protected from contact with possible infection. Antifungal and antibacterial agents are prescribed, and body temperature is constantly monitored.

Cell engraftment. The patient’s well-being gradually begins to improve and return to normal.

Restoring bone marrow function takes several months. During this entire period, the patient is under the supervision of a doctor.

Chemotherapy

For chronic myeloid leukemia, several groups of drugs are used:

Hydroxyurea drugs that inhibit DNA synthesis in tumor cells. Side effects may include digestive disorders and allergies.

Among modern drugs, protein tyrosine kinase inhibitors are often prescribed. These drugs inhibit the growth of pathological cells, stimulate their death, and can be used at any stage of the disease. Side effects may include cramps, muscle pain, diarrhea, and nausea.

Interferon is prescribed after normalization of the number of leukocytes in the blood to suppress the formation and growth and restore the patient’s own immunity.

Possible side effects include depression, mood swings, weight loss, autoimmune pathologies and neuroses.

Radiation therapy

Radiation therapy for chronic myeloid leukemia is carried out in the absence of effect from chemotherapy or in preparation for a bone marrow transplant.

Gamma irradiation of the spleen helps slow down tumor growth.

Splenectomy

In rare cases, removal of the spleen or, in medical terms, splenectomy may be prescribed. Indications for this include a sharp decrease in platelets or severe abdominal pain, a significant increase in the organ or the threat of its rupture.

Leukocytophoresis

A significant increase in leukocytes can lead to serious complications, such as microthrombosis and retinal edema. In order to prevent them, the doctor may prescribe leukocytophoresis.

This procedure is similar to regular blood purification, only in this case tumor cells are removed from it. This improves the patient's condition and prevents complications. Leukocytophoresis can also be used in combination with chemotherapy to improve the effect of treatment.

In July of this year, the US Food and Drug Administration (FDA) for the first time in the history of domestic pharmaceuticals assigned orphan status to a Russian experimental drug. It was a drug for the treatment of chronic myeloid leukemia. MedAboutMe figured out what kind of disease this is and whether there are chances to get rid of it completely, for example, with the help of a new remedy created by our scientists.

CML: history of discovery

The history of the discovery of chronic myeloid leukemia (CML) and its treatment is closely connected with the history of science and medicine. Medical acquaintance with CML began in 1811, when Peter Cullen described a patient with acute inflammation of the spleen and “milky blood.” In 1845, when microscopes were already available and methods for staining cells had not yet been invented, Scottish pathologist John Bennett described in his articles tissues of an enlarged spleen and liver obtained from two patients who died “of blood poisoning.” In particular, Bennett presented images of leukocythemia - unusual blood cells. And literally 1.5 months later, a similar picture was published by another pathologist - the German Rudolf Virchow. And he was the first to suggest that the issue was not sepsis, but a previously unknown disease. Another 2 years later, Virchow discovered a similar case and for the first time announced the name of the alleged disease - “splenic leukemia.” So CML is the first disease called "leukemia".

It should be noted that the medical community reacted negatively to Virchow’s reports. One of his colleagues even said: “We already have enough diseases, we don’t need new ones!” But history took its course. In 1846, a detailed description of the disease was published, made not by a pathologist, but by a doctor who treated a still living person. And since 1880, with the advent of methods for staining cells for microscopic examination, scientists have been able not only to examine CML cells in detail, but also to identify different forms of “leukemia.”

In the 1950s, American researchers P. Nowell and D. Hungerford discovered that all patients with CML had one of their chromosomes shortened. Moreover, the data they obtained indicated the clonal nature of the disease, that is, it developed from a single cell that received additional growth advantages due to mutation. This ultimately led to an increase in the clone of diseased cells. After the name of the city in which this discovery was made, the shortened chromosome became known as the “Philadelphia” chromosome (Ph+). But later it turned out that it was not just a matter of a shortened chromosome...

What is chronic myeloid leukemia?

Today it is known that chronic myeloid leukemia develops as a result of translocation - the exchange of sections between the 9th and 22nd chromosomes. That is, the 9th chromosome loses a piece, and the 22nd attaches it to itself. The main problem is that during transfer this section of DNA is inserted into the area where the ABL oncogene is located. In humans, this gene encodes a protein necessary for hematopoiesis, and its separate domain plays the role of a tyrosine kinase enzyme and triggers the processes of cell proliferation (their active reproduction). Another domain is designed to stop tyrosine kinase activity. When a section is moved from the 9th chromosome, a new gene BCR-ABL is formed - this is a marker of chronic myeloid leukemia. The protein that is supposed to block tyrosine kinase function no longer works. Proliferation is launched “to the fullest” and, in addition, apoptosis (the programmed death of old and damaged cells) is canceled.

Stem cells with a translocation from chromosome 9 to 22 are called Ph-positive. Patients with CML have both Ph-positive and Ph-negative cells. And the former, due to their uncontrolled activity, are crowding out the latter.

How does CML manifest?

To describe chronic myeloid leukemia, they do not use a list of symptoms - it is too extensive, but a list of syndromes, that is, symptom complexes. Accordingly, they distinguish:

Tumor intoxication syndrome.

The patient is anemic, feels weak, sweating, pain in joints and bones, and constant itching. The person loses weight, his appetite worsens, and he has a low-grade fever.

Tumor proliferation syndrome (that is, uncontrolled proliferation of cells and their transformation into tumor cells).

An enlarged spleen leads to pain in the left side. The liver is often also enlarged.

Anemic syndrome.

Weakness, constant shortness of breath, tachycardia, low blood pressure, exercise intolerance, pallor of the mucous membranes and skin. Against this background, existing cardiovascular diseases may become more active.

Hemorrhagic syndrome.

It develops against the background of platelet deficiency (thrombocytopenia) and manifests itself in the form of bleeding even with minor injuries, rashes in the form of petechiae (small pinpoint bruises) and bruises.

Thrombotic manifestations.

The risk of developing thromboembolism of organs and tissues and thrombosis increases significantly.

Three phases of the disease

There are three main phases during CML:

Chronic phase - it is diagnosed in 80% of patients; this is the initial phase of the disease. Acceleration phase - at this stage, 8-10% of patients are identified, the pathological process is in full swing. Blast crisis - only 1-2% see doctors for the first time at this stage. The disease in this phase is most aggressive.

The life span of patients in whom the disease was detected in the acceleration phase and at the blast crisis stage is short - 6-12 months.

Who has CML?

This is a rare disease. It occurs with a frequency of 1.4-1.6 cases per 100 thousand adults. It is mainly adults who suffer from chronic myeloid leukemia: this disease accounts for 20% of all leukemia among them and only 2% in children. More often, the disease first appears in patients aged 40-50 years.

Men get sick slightly more often than women, the ratio is 1.4:1.

In our country, there are 8 thousand people diagnosed with chronic myeloid leukemia. The incidence is 0.08 cases per 100 thousand Russians.

Treatment of CML: from arsenic to modern chemotherapy CML and arsenic

Since 1865, they began to try to treat the new disease. Arsenic was especially loved by doctors in the mid-to-late 19th century. It was used in the form of a “Fowler’s solution,” which was a 1% aqueous-alcohol solution of potassium arsenite. In order not to confuse the drug with water, it was flavored with lavender. This remedy was invented back in the 13th century by Thomas Fowler, and it was used to treat almost everything that could not be treated in other ways: asthma, syphilis, eczema, epilepsy, rheumatism... It is not surprising that it was decided to try the arsenic panacea against newly discovered leukemia.

And in general, a certain effect was achieved. The spleen became smaller, the patients felt better. True, not for long - the life of a person with CML after diagnosis, even with treatment, did not exceed 2-3 years.

Radiation therapy for CML In 1895, science discovered a powerful tool for diagnosis and therapy - x-rays. For this discovery, K. Roentgen received the Nobel Prize in Physics, but doctors quickly realized how X-ray radiation could be used to treat patients. The American N. Senn first used radiation therapy for the treatment of CML in 1903. The spleen treated with X-rays actually became smaller, the number of leukocytes decreased - it seemed that a solution had been found. But, alas, over time it turned out that the effect of radiation therapy lasts about six months, and with each subsequent time it becomes weaker and shorter.

And yet, in the absence of other means, X-ray therapy remained the only method for treating patients with CML almost until the middle of the 20th century. The disease was brought into remission, which lasted about six months, and on average such a patient lived 3-3.5 years. Only 15% of patients managed to survive 5 years.

Chemotherapy for CML The era of chemotherapy for CML was opened by the Englishman D. Galton. He was the first to use myelosan, synthesized in 1953 by his compatriots, to fight the disease. This drug has many names: Americans call it busulfan, the French call it mizulban, the British call it mileran, and myelosan is the common name in Russia.

The new medicine seemed like a miracle. It was well tolerated and showed high efficacy, even in people who did not respond to radiation therapy. The drug made it possible to keep the level of leukocytes under control and prevented the spleen from growing. Patients with CML stopped becoming disabled already in the first year of the disease - instead of hospitals, they were able to live at home and lead a full life. And its duration also increased and amounted to 3.5-4.5 years. 30-40% of patients survived to 5 years. The reason for this was the absence of severe side effects characteristic of x-ray therapy: anemia, cachexia (exhaustion), infections.

Myelosan extended life, patients began to live longer and, therefore, more patients began to survive to the blast crisis phase and the terminal stage of the disease. The death of such patients was not easy. Fluctuations in temperature, alternating with attacks of chills, cachexia, rapid enlargement of the spleen and liver, weakness and, most importantly, severe pain. A dispute even arose: should myelosan not be considered the cause of the development of blast crisis? After all, such a number of cases were not observed with radiotherapy. But in 1959, a study was conducted in which it was proven that after 3 years from its start, 62% of patients treated with myelosan remained alive, and only a third of the group treated with x-rays. Overall, life expectancy with myelosan was one year longer than with radiation therapy. This study was the final point in making the decision to almost completely abandon radiotherapy as the main method of treating CML.

Scientists continued to search for a cure. The effectiveness of the use of hydroxyurea, which blocked the enzyme ribonucleotidase involved in DNA synthesis, has been proven. And this substance extended the life of patients with CML by another 10 months.

And in 1957, medicine received interferons at its disposal - and a new stage began in the treatment of CML. With their help, in just a couple of months it was possible to put the patient into remission, and in some patients the number of Ph-positive cells decreased.

By combining interferons with other drugs, it was possible to achieve that from 27% to 53% of patients had every chance of living 10 years from the moment of diagnosis, and in groups where the disease was detected at very early stages, they could expect 10 years of life from 70 % to 89% of patients.

The main thing that did not suit doctors and scientists about interferons was that it was still not a method of treating CML. It was not possible to completely get rid of Ph-positive cells even with their help.

Stem cell transplant

At the end of the last century, the method of transplantation of geopoietic stem cells began to gain popularity. We were already talking about 10- and even 20-year survival rates - and these were quite realistic figures for a third of patients treated with this method. But, firstly, this method did not cure the patient completely. And secondly, only 20-25% of people with chronic myeloid leukemia have a chance of finding a compatible related donor. If we are talking about an unrelated donor, the likelihood of finding him is much lower. That is, initially not all patients can be treated with this method.

Tyrosine kinase inhibitors

Finally, scientists managed to find a weak point in the disease. A real victory over CML was imatinib (Gleevec) - this substance is built into the “pocket” of the ABL-tyrosine kinase protein and blocks its work. The effectiveness of the new drug was so high that the FDA quickly registered it and gave the go-ahead for use. The results of treatment with imatinib were significantly better than with any other treatment.

But there is no perfection in the world. It turned out that over time, many patients develop resistance to this medicine, and increasing the dose is too toxic for the body.

In the course of intensive pharmaceutical research, second generation tyrosine kinase inhibitors were created - nilotinib (Tasigna) and dasatinib (Sprycel). Today they are prescribed if there is a risk that imatinib therapy may stop working. Often such drugs are combined with interferons and other drugs that enhance the effect. And today it is the best working medicine that medicine has for patients with CML. Thanks to them, 80% of patients live for at least 10 years, and in a third of cases they die not from CML, but from other diseases.

In Russia, patients within the framework of the “7 nosologies” program receive imatinib free of charge (the cost of treatment per year ranges from 200 thousand to 1 million rubles). But those of them whose body has developed resistance to imatinib have a hard time. Second generation tyrosine kinase inhibitors in our country are not covered under the government guarantee program. That is, treatment must be carried out at the expense of the budget of the region where the person lives. This means endlessly delaying the allocation of money and, as a result, receiving the medicine too late.

At the beginning of the article, we mentioned the achievement of Russian researchers from the Fusion Pharma company, which is part of the biomedical technology cluster of the Skolkovo Foundation. Scientists have developed a selective third-generation tyrosine kinase inhibitor. It is assumed that the molecule they created, called PF-114, will be even more effective in suppressing the activity of the protein, which is encoded by the BCR-ABL gene. Currently, researchers have begun phase 1 clinical trials. And the fact that the FDA assigned orphan status to the drug indicates the significance and importance of these trials not only for Russia, but also for the global medical community. Perhaps it is our scientists who will take another step towards a complete cure for chronic myeloid leukemia.

Conclusions Over the 200 years since the disease was first described, medicine has extended the life of a patient with CML from several months to a full life of decades. But the question of a complete cure still remains open. Studies show that some patients are completely cured during long-term use of tyrosine kinase inhibitors. But some do not; after stopping the medication, they develop a relapse of the disease. How to distinguish the first from the second is still unclear. Research continues.