Myeloid leukemia - what is it? Chronic myeloid leukemia: causes, treatment, prognosis. Chronic myeloid leukemia

Hematologist

Higher education:

Hematologist

Samara State Medical University (SamSMU, KMI)

Level of education - Specialist
1993-1999

Additional education:

"Hematology"

Russian Medical Academy of Postgraduate Education

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

The essence of pathology

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

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

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

Causes of the disease

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

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

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

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

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

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

Classification of chronic myeloid leukemia

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

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

According to the clinical picture, the pathology can be:

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

There are three degrees of severity of the disease:

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

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

Symptoms of chronic myeloid leukemia

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

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

In the future, you may experience:

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

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

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

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

Diagnosis of chronic myeloid leukemia

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

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

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

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

Pathology therapy

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

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

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

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

Pathology progression

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

Advanced stage of pathology

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

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

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

Alpha interferon

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

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

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

There are many diagnoses whose names mean little to ordinary citizens. One such disease is chronic myeloid leukemia. Reviews from patients with this disease are nevertheless capable of attracting attention, since this disease can not only cause significant damage to health, but also lead to a fatal outcome.

The essence of the disease

If you hear a diagnosis such as “chronic myeloid leukemia,” then it is important to understand that we are talking about a serious tumor disease of the hematopoietic system, which affects the hematopoietic stem cells of the bone marrow. It can be classified as a group of leukemias, which are characterized by large formations of granulocytes in the blood.

At the very beginning of its development, myeloid leukemia manifests itself through an increase in the number of leukocytes, reaching almost 20,000/μl. Moreover, in the progressive phase this figure changes to 400,000/μl. It is worth noting the fact that both the hemogram and the myelogram show a predominance of cells with different degrees of maturity. We are talking about promyelocytes, metamyelocytes, band and myelocytes. In the case of the development of myeloid leukemia, changes are detected in the 21st and 22nd chromosomes.

This disease in most cases leads to a noticeable increase in the content of basophils and eosinophils in the blood. This fact is evidence that we are dealing with a severe form of the disease. In patients who suffer from such an oncological disease, splenomegaly develops, and a large number of myeloblasts are recorded in the bone marrow and blood.

How does the disease begin?

Chronic myeloid leukemia pathogenesis is quite interesting. Initially, a somatic mutation of a pluripotent hematopoietic blood stem cell can be identified as a trigger factor in the development of this disease. The main role in the mutation process is played by the cross-translocation of chromosomal material between the 22nd and 9th chromosomes. In this case, the Ph chromosome is formed.

There are cases (no more than 5%) when the Ph chromosome cannot be detected during a standard cytogenetic study. Although molecular genetic research reveals an oncogene.

Chronic myeloid leukemia can also develop due to exposure to various chemical compounds and radiation. Most often this disease is diagnosed in adulthood, extremely rarely in adolescents and children. As for gender, this type of tumor is recorded with equal frequency in both men and women aged 40 to 70 years.

Despite all the experience of doctors, the etiology of the development of myeloid leukemia is still not completely clear. Experts suggest that acute and chronic myeloid leukemia develops due to a disorder of the chromosomal apparatus, which, in turn, is caused by the influence of mutagens or hereditary factors.

Speaking about the effects of chemical mutagens, it is worth paying attention to the fact that quite a few cases have been recorded in which people exposed to benzene or using cytostatic drugs (Mustargen, Imuran, Sarcozoline, Leukeran, etc.) , myeloid leukemia developed.

Chronic myeloid leukemia: stages

With a diagnosis such as “myeloid leukemia,” three stages of development of this disease are distinguished:

Initial. Characterized by an enlarged spleen and a stable increase in leukocytes in the blood. The patient's condition is considered dynamically, without using radical treatment measures. The disease, as a rule, is diagnosed already at the stage of total generalization of the tumor in the bone marrow. At the same time, in the spleen, and in some cases in the liver, extensive proliferation of tumor cells is observed, which is characteristic of the advanced stage.

Expanded. Clinical signs at this stage begin to dominate, and the patient is prescribed treatment using specific drugs. At this stage, the myeloid tissue in the bone marrow, liver and spleen grows, and the fat in the flat bones is virtually completely replaced. There is also a sharp predominance of the granulocytic lineage and three-line proliferation. It is worth noting that in the advanced stage, lymph nodes are extremely rarely affected by the leukemic process. In some cases, myelofibrosis may develop in the bone marrow. There is a possibility of developing pneumosclerosis. As for the infiltration of the liver by tumor cells, in most cases it is quite pronounced.

Terminal. At this stage of the disease, thrombocytopenia and anemia progress. Manifestations of various complications (infection, bleeding, etc.) become obvious. The development of a second tumor from immature stem cells is often observed.

What life expectancy should you expect?

If we talk about people who have had to deal with chronic myeloid leukemia, it is worth noting that modern treatment methods have significantly increased the chances of such patients for a relatively long life. Due to the fact that discoveries have been made in the field of pathogenetic mechanisms of the development of the disease, which have made it possible to develop drugs that can act on the mutated gene, with a diagnosis such as chronic myeloid leukemia, the life expectancy of patients can be 30-40 years from the moment the disease is diagnosed. But this is possible provided that the tumor was benign (slow enlargement of the lymph nodes).

In the case of the development of a progressive or classic form, the average is from 6 to 8 years from the moment the disease was diagnosed. But in each individual case, the number of years that the patient can enjoy is significantly influenced by the measures taken during the treatment process, as well as by the form of the disease.

On average, according to statistics, up to 10% of patients die within the first two years after detection of the disease and 20% in subsequent years. Many patients with myeloid leukemia die within 4 years after the diagnosis was made.

Clinical picture

The development of a disease such as chronic myeloid leukemia occurs gradually. At first, the patient feels a deterioration in his general health, fatigue, weakness, and in some cases moderate pain in the left hypochondrium. After the study, an enlarged spleen is often recorded, and a blood test reveals significant neutrophilic leukocytosis, characterized by a shift in the leukocyte count to the left due to the action of myelocytes with an increased content of basophils, eosinophils and platelets. When the time comes for the full picture of the disease, patients experience loss of ability to work due to sleep disturbances, sweating, a steady increase in general weakness, a significant increase in temperature, pain in the spleen and bones. There is also a loss of weight and appetite. At this stage of the disease, the spleen and liver are significantly enlarged.

At the same time, chronic myeloid leukemia, the symptoms of which differ depending on the stage of development of the disease, already in the initial stage leads to a predominance of eosinophils, granular leukocytes and basophils in the bone marrow. This growth occurs due to a decrease in other leukocytes, normoblasts and red blood cells. If the disease process begins to worsen, the number of immature myeloblasts and granulocytes increases significantly, and hemocytoblasts begin to appear.

Blast crisis in chronic myeloid leukemia leads to total metaplasia. In this case, there is a high fever, during which there are no signs of infection. Hemorrhagic syndrome develops (intestinal, uterine, mucous bleeding, etc.), leukemides in the skin, ossalgia, lymph nodes enlarge, complete resistance to cytostatic therapy and infectious complications are recorded.

If it was not possible to significantly influence the course of the disease (or such attempts were not made at all), then the condition of the patients will progressively worsen, and thrombocytopenia will appear (the phenomena of hemorrhagic diathesis make themselves felt) and severe anemia. Due to the fact that the size of the liver and spleen is growing rapidly, the volume of the abdomen noticeably increases, the condition of the diaphragm becomes high, the abdominal organs are compressed, and, as a consequence of these factors, the respiratory excursion of the lungs begins to decrease. Moreover, the position of the heart changes.

When chronic myeloid leukemia develops to this level, dizziness, shortness of breath, palpitations and headache appear against the background of pronounced anemia.

Monocyte crisis in myeloid leukemia

Regarding the topic of monocytic crisis, it should be noted that this is a rather rare phenomenon, during which young, atypical and mature monocytes appear and grow in the bone marrow and blood. Due to the fact that the bone marrow barriers are broken, at the terminal stage of the disease fragments of megakaryocyte nuclei appear in the blood. One of the most important elements of the terminal stage during a monocytic crisis is the inhibition of normal hematopoiesis (regardless of the morphological picture). The disease process is aggravated due to the development of thrombocytopenia, anemia and granulocytopenia.

In some patients, rapid enlargement of the spleen may be observed.

Diagnostics

The fact of progression of a disease such as chronic myeloid leukemia, the prognosis of which can be quite bleak, is determined through a whole complex of clinical data and specific changes in the process of hematopoiesis. In this case, histological studies, histograms and myelograms must be taken into account. If the clinical and hematological picture does not look clear enough and there is not enough data to confidently make a diagnosis, then doctors focus on detecting the Ph chromosome in monocytes, megakaryocytes, erythrocytes and granulocytes of the bone marrow.

In some cases, it is necessary to differentiate chronic myeloid leukemia. Diagnosis, which can be defined as differential, is aimed at identifying the typical picture of the disease with hyperleukocytosis and splenomegaly. If the option is atypical, then a histological examination of the spleen punctate is performed, as well as a myelogram study.

Certain difficulties can be observed when patients are admitted to the hospital in a state of blast crisis, the symptoms of which are very similar to myeloid leukemia. In such a situation, data from a thoroughly collected anamnesis, cytochemical and cytogenetic studies significantly help. Often chronic myeloid leukemia must be differentiated from osteomyelofibrosis, in which intense myeloid metaplasia can be observed in the lymph nodes, spleen, liver, as well as significant splenomegaly.

There are situations, and they are not uncommon, when a blood test helps to identify chronic myeloid leukemia in patients who have undergone a routine examination (in the absence of complaints and asymptomatic disease).

Diffuse myelosclerosis can be excluded by x-ray examination of bones, which reveals multiple areas of sclerosis in flat bones. Another disease that, although rare, still has to be differentiated from myeloid leukemia, is hemorrhagic thrombocythemia. It can be characterized by leukocytosis with a shift to the left and enlargement of the spleen.

Laboratory tests for the diagnosis of myeloid leukemia

In order to accurately determine the patient’s condition if chronic myeloid leukemia is suspected, a blood test can be performed in several directions:

Blood chemistry. It is used to identify disorders in the liver and kidneys that are a consequence of the use of certain cytostatic agents or were provoked by the spread of leukemia cells.

- Clinical blood test (complete). Necessary for measuring the level of various cells: platelets, leukocytes and red blood cells. In most patients who have had to deal with a disease such as chronic myeloid leukemia, the analysis reveals a large number of immature white cells. Sometimes a low platelet or red blood cell count may occur. Such results are not a basis for determining leukemia without an additional test that is aimed at examining the bone marrow.

Examination of bone marrow and blood samples under a microscope by a pathologist. In this case, the shape and size of the cells are studied. Immature cells are identified as blasts or myeloblasts. The number of hematopoietic cells in the bone marrow is also counted. The term “cellularity” is applicable to this process. In those with chronic myelogenous leukemia, the bone marrow tends to be hypercellular (large concentrations of hematopoietic cells and a high content of malignant cells).

Treatment

For a disease such as chronic myeloid leukemia, treatment is determined depending on the stage of development of tumor cells. If we are talking about mild clinical and hematological manifestations in the chronic stage of the disease, then nutritious nutrition enriched with vitamins, regular follow-up and restorative therapy should be considered as relevant therapeutic measures. Interferon can have a beneficial effect on the course of the disease.

If leukocytosis develops, doctors prescribe Myelosan (2-4 mg/day). If you have to deal with higher leukocytosis, then the dose of Myelosan can rise to 6 or even 8 mg/day. You should expect the manifestation of a cytopenic effect no earlier than 10 days after the first dose of the drug. A decrease in the size of the spleen and a cytopenic effect occurs on average during the 3-6th week of treatment, if the total dose of the drug was from 200 to 300 mg. Further therapy involves taking 2-4 mg of Myelosan once a week, which at this stage has a supporting effect. If the first signs of exacerbation make themselves known, myelosanotherapy is performed.

It is possible to use a technique such as radiation therapy, but only when splenomegaly is identified as the main clinical symptom. For the treatment of patients whose disease is in a progressive stage, poly- and monochemotherapy is relevant. If significant leukocytosis is recorded, if the effect of Myelosan is not sufficiently effective, Myelobromol (125-250 mg per day) is prescribed. At the same time, strict monitoring of peripheral blood parameters is carried out.

If significant splenomegaly develops, Dopan is prescribed (single dose 6-10 g/day). Patients take the drug once for 4-10 days. The intervals between doses are determined depending on the degree and rate of decrease in the number of leukocytes, as well as the size of the spleen. As soon as the decrease in leukocytes reaches an acceptable level, the use of Dopan is stopped.

If a patient develops resistance to Dopan, Myelosan, radiation therapy and Myelobromol, Hexaphosphamide is prescribed for treatment. In order to effectively influence the course of the disease in the progressive stage, the CVAMP and AVAMP programs are used.

If resistance to cytostatic therapy develops in a disease such as chronic myeloid leukemia, treatment in the progression stage will be focused on the use of leukocytopheresis in combination with a specific polychemotherapy regimen. As an urgent indication for leukocytopheresis, clinical signs of stasis in the vessels of the brain (a feeling of heaviness in the head, decreased hearing, headaches), which are caused by hyperthrombocytosis and hyperleukocytosis, can be identified.

If a blast crisis is detected, various chemotherapy programs used for leukemia can be considered relevant. Indications for transfusions of red blood cells, platelet concentrate and antibacterial therapy are infectious complications, the development of anemia and thrombocytopenic hemorrhage.

Regarding the chronic stage of the disease, it is worth noting that at this stage of development of myeloid leukemia, bone marrow transplantation is quite effective. This technique is capable of ensuring the development of clinical and hematological remission in 70% of cases.

An urgent indication for splenectomy in chronic myeloid leukemia is the threat of rupture or rupture of the spleen. Relative indications include severe abdominal discomfort.

Radiation therapy is indicated for those patients in whom extramedullary tumor formations that pose a threat to life have been identified.

Chronic myeloid leukemia: reviews

According to patients, such a diagnosis is too serious to ignore. By studying the testimonies of various patients, the real possibility of defeating the disease becomes obvious. To do this, you need to undergo timely diagnosis and subsequent treatment. Only with the participation of highly qualified specialists is there a chance to defeat chronic myeloid leukemia with minimal losses to health.

Myeloid leukemia is not an independent disease, but refers to a condition characterized by increased and uncontrolled growth of myeloid lineage cells in the red bone marrow and their accumulation in the bloodstream.

Leukemia is also popularly called blood cancer, but the term is not correct. Nosologically, it is customary to distinguish two diseases associated with this condition - chronic (CML) and acute myeloid leukemia (AML).

In AML, massive division of myelopoiesis precursor cells (blasts) occurs, which cannot differentiate into mature ones. According to WHO statistics, AML accounts for about 80% of all other types of leukemia. According to surveillance data, the disease most often affects patients under 15 and after 60 years of age. In terms of gender, AML is less common in women.

Unlike AML, in CML malignant cells retain the ability to differentiate into mature forms. About 15% of all cases of leukemia are CML. The annual incidence is approximately 1.6 per 100,000 population. Most often, the disease affects patients in the age group 20-50 years. In gender ratio, men get sick more often than women, approximately 1.5:1.

Classification

In addition to the classical ICD, there are several classifications that allow you to obtain an accurate description of the pathological process. For acute myeloid leukemia, the most relevant is the French-American-British (FAB) classification, based on the type and maturity of the cells from which leukemia develops.

According to the hematological classification, chronic myeloid leukemia has about 5 main subtypes.

According to the International Classification of Diseases, 10th revision (ICD-10), each subtype of the disease should be assigned a specific code:

C92.0 – Acute myeloid leukemia.

C92.1 – Chronic myeloblastic leukemia.

C92.2 – Atypical chronic myeloid leukemia.

C92.4 – Acute promyelocytic leukemia.

C92.5 – Acute myelomonocytic leukemia.

C92.7 – Other myeloblastic leukemia.

C92.9 – Myeloblastic leukemia, unspecified.

C93.1 – Chronic myelomonocytic leukemia.

Causes and risk factors for developing AML

Acute myeloid leukemia is caused by damage to the DNA of developing cells of the myeloid lineage of the bone marrow, which subsequently provokes abnormal production of blood components. In AML, the bone marrow produces immature cells called myeloblasts. These abnormal cells cannot function properly and, when dividing and growing excessively, begin to crowd out healthy bone marrow elements.

In most cases, it is unclear what causes the DNA mutation, but several factors have been found to contribute to the development of AML, including antecedent hematologic disorders, hereditary causes, environmental exposures, and drug influences. However, most patients with new-onset AML do not have an identifiable cause for their disease.

Antecedent hematological disorders. The most common cause of development is myelodysplastic syndrome (MDS). It is a bone marrow disease of unknown etiology that most often occurs in older patients and presents with progressive cytopenia over months or years. There are also gradations of risk in patients with this syndrome. For example, patients with refractory anemia with ringed sideroblasts have a significantly lower risk of developing AML than patients with MDS with an increased number of blast cells.

Congenital disorders. Congenital conditions that predispose patients to the development of AML include Bloom syndrome, Down syndrome, congenital neutropenia, Fanconi anemia, and neurofibromatosis. Typically, these patients develop acute myeloid leukemia from childhood, but can also appear in adulthood.

In clinical studies, it was noted that the risk of spreading AML increases significantly with regular exposure to benzene. This chemical is used as a solvent in various industries (chemical and oil refineries, as well as in the production of rubber and footwear). Benzene is found in glue, cleaning products, paints and cigarette smoke. Exposure to formaldehyde is also associated with AML, but the exact impact is not yet known.

Chemotherapy. Patients who have previously undergone chemotherapy are more likely to develop AML. Some drugs are closely associated with the development of secondary leukemia (Mechlorethamine, Procarbazine, Chlorambucil, Melphalan, Etoposide, Teniposide and Cyclophosphamide).

The risk increases if the patient receives radiation therapy at the same time as taking these chemotherapy drugs. Secondary leukemias occur approximately 10 years after treatment for Hodgkin's disease, non-Hodgkin's lymphoma, or childhood acute lymphocytic leukemia. Secondary leukemias can also occur after treatment for breast, ovarian, or other cancers.

Exposure to radiation. Exposure to high levels of radiation is a known risk factor for AML as well as acute lymphoblastic leukemia. This was first noted among Japanese survivors of the nuclear bombing of Hiroshima and Nagasaki. Within 6-8 years after the tragic events, many Japanese people showed signs of acute myeloid leukemia.

Adverse radiation effects can be observed during radiation therapy for cancer treatment, as well as during certain types of diagnostic tests (radiography, fluoroscopy, computed tomography).

The causes are unknown, but it has been noted that men suffer from AML more often than women. Also, the disease is more common in people of the Caucasian race. Unproven risk factors include living in an area with high electromagnetic radiation, exposure to pesticides, bleaches and hair dyes.

Causes and risk factors for developing CML

In a healthy person, the cells of the body contain 23 pairs of chromosomes in their nucleus. In people suffering from CML, a disorder in the structure of chromosomes occurs in the bone marrow cells, which consists of moving a section from the 22nd chromosome to the 9th. The ultra-short 22nd chromosome, also called the Philadelphia chromosome (after the city where it was first discovered), is present in the blood of 90% of people suffering from CML.

Against the background of these chromosomal changes, new genes are formed that begin to overproduce the enzyme tyrosine kinase. Subsequently, a large amount of tyrosine kinase leads to abnormal division of bone marrow cells, which contributes to the development of chronic myeloid leukemia. Abnormal white blood cells do not develop or die as normal, but they divide in large numbers, crowd out healthy blood cells, and damage bone marrow.

The exact causes of AML have not yet been elucidated. It is now generally accepted that acute myeloid leukemia develops against the background of the accumulation of mutations in the precursor cells of myelopoiesis. With some exceptions, factors that increase the risk of developing CML are similar to AML.

Weakened immunity. Clinical studies have shown that people suffering from immunosuppression, such as AIDS, are 3 times more likely to develop CML compared to the general population. The adverse effects of cytostatic drugs have also been noted in people forced to take them after organ transplantation. In this case, the risk increases by 2 times.

The reasons are not fully understood, but after statistical analysis, it appears that patients with inflammatory bowel diseases such as ulcerative colitis or Crohn's disease have a higher chance of developing CML compared to the general population.

Pesticides. A number of studies have provided evidence that men exposed to pesticides on a daily basis (farmers, agricultural workers) have an increased risk of developing chronic myeloid leukemia. When compared to the general population, the risk increases by approximately 40%.

Gender, age and other risk factors. As with AML, CML is more likely to affect Caucasian men. There were 4 studies that noted the adverse effects of obesity. Being overweight increases your chance of getting sick by about 25%.

Symptoms

Most clinical manifestations and signs of myeloid leukemia, both acute and chronic, are associated with the displacement of healthy bone marrow sprouts by abnormal cells. For this reason, 4 main syndromes are distinguished during the course of diseases:

• Anemic. A decrease in the number of red blood cells causes fatigue, increased heart rate, pallor and shortness of breath.
• Immunodeficient. The lack of normal white blood cell production makes patients more susceptible to infection because the abnormal cells lack the mechanisms to promote a full immune response.
• Intoxicating. Early signs of myeloid leukemia are often nonspecific and may be similar to symptoms of the flu or other colds. Common symptoms include: fever, fatigue, weight loss, loss of appetite, shortness of breath, anemia, petechiae (spots on the skin caused by bleeding), bone and joint pain.
• Hemorrhagic. Decreased platelet synthesis leads to mild bruising or bleeding with minor injury.

In addition, with CML, in more than 50% of cases, an enlarged spleen is observed. It can reach such large sizes that it begins to compress the abdominal organs. An enlarged spleen sometimes accompanies AML, but usually the process is slow and painless.

Due to leukocyte infiltration, some patients experience swelling of the gums. In rare cases, the primary symptom of AML is the formation of a dense leukemic mass or tumor (chloroma) outside the bone marrow. Very rarely, AML causes enlarged lymph nodes and paraneoplastic inflammation of the skin.

Stages

Dividing the course of chronic lymphocytic leukemia into phases allows doctors to more competently plan treatment and predict the outcome of the disease.

Standards have not yet been developed for determining the staging of acute myeloid leukemia, but it is customary to distinguish 3 key phases based on the general course of the disease.

The most common types of myeloid leukemia

About 25% of all cases of AML are due to maturing acute myeloblastic leukemia (M2). The subtype is characterized by the movement of part of the 8th chromosome to the 21st. On both sides of the splice, a new set of DNA is formed from fragments that previously encoded the RUNX1 and ETO proteins. Then these two sequences are connected and begin to encode one large protein called M2 AML, which allows the cell to divide unhindered.

The most common type of CML is chronic granulocytic leukemia. That is, any pathological factor that provokes changes in the chromosome set affects blast cells, from which granulocytes are then formed. This form of CML occurs in approximately 95% of cases.

Diagnostics

Several tests may be ordered to confirm the diagnosis of leukemia. Diagnostics also allows you to determine the type of disease and, based on the data obtained, select the best treatment method. The basis of the diagnostic process when confirming the diagnosis of acute or chronic myeloid leukemia is laboratory research methods.

Complete blood count (CBC). In most patients, a preliminary diagnosis of myeloid leukemia is made after OAC. The essence of the test is to count blood cells (erythrocytes, leukocytes, platelets). A CBC is often performed as part of a regular medical examination. People suffering from CML will have a marked increase in white blood cell counts (usually due to granulocytes) associated with thrombocytosis and basophilia. In addition, elements of immature leukopoiesis are observed in the blood formula. When other bone marrow sprouts are suppressed, the number of red blood cells decreases in patients. Due to the increase in the total number of leukocytes, leukemia is sometimes called leukemia.

Aspiration and biopsy. No specific tumor markers have been found to identify myeloid leukemia, so in most cases they are diagnosed by a combination of biopsy and aspiration. This is the only sure way to confirm the diagnosis. An aspiration is a procedure that uses a thin needle to remove the liquid part of the bone marrow, while a biopsy takes a sample of the solid part. These 2 procedures are very similar and are often performed simultaneously to obtain more accurate information about the condition of the bone marrow.

A typical site for aspiration and biopsy is the iliac crest of the pelvis. After collecting biological material, a specialist in the field of pathological anatomy conducts a detailed examination of the obtained samples. One of the main criteria indicating AML in a patient is the presence of more than 20% blasts in the blood and aspirate.

The test involves testing leukemia cells for certain genes, proteins and other factors that indicate they are malignant. Based on this study, individualized targeted therapy may be developed in the future.

Genetic research. Allows you to determine the genotype of AML and select the optimal treatment option for the patient. In addition, the test results can be used in the future to monitor the treatment process.

Cytogenetic study. A type of genetic testing that is used to analyze a cell's chromosomes. Sometimes this test can be done on peripheral blood cells, but tissue samples obtained from the bone marrow are needed to make an accurate diagnosis.

After treatment for CML is initiated, cytogenetic and/or molecular testing is repeated on a different bone marrow sample to re-enumerate the number of cells containing the Philadelphia chromosome and evaluate the effectiveness of chemotherapy.

For most patients, the presence of the Philadelphia chromosome and the BCR-ABL hybrid gene is the main marker indicating the presence of CML. In a small number of patients, the Philadelphia chromosome is not detected by conventional tests, even despite the presence of the BCR-ABL hybrid gene and an increase in the number of blood cells. However, the treatment tactics in this case will be the same as in patients with a detectable Philadelphia chromosome.

Imaging research methods. They are prescribed to evaluate the effect of leukemia on other parts of the body. For example, CT scans and ultrasounds are sometimes used to view and measure the size of the spleen in patients with leukemia.

How fast is it developing?

No specific techniques have been developed to predict the duration of the chronic phase and the onset of blast crisis in CML. However, it is generally accepted that unfavorable factors include a sharp increase in the level of leukocytes, hepatosplenomegaly, and an increase in the percentage of blasts in the red bone marrow. The same applies to AML.

Features of the course and treatment in special categories of patients

The course of the disease does not differ much depending on age and gender. The only factors that need to be taken into account are the weight and age of the patients, as these characteristics affect the dosage of the drugs.

Pregnancy. During pregnancy, the diagnosis of myeloblastic leukemia is very rare, approximately 1 in 300,000 cases. Moreover, if timely treatment is not started, there is a high probability of spontaneous abortion. In addition, an increased level of blast cells in the blood can cause intrauterine growth retardation, provoke premature birth, or lead to intrauterine fetal death.

Despite the presence of a hematoplacental barrier that protects the fetus from the effects of chemotherapy, termination of pregnancy may be recommended in the early stages. If the diagnosis was made in the 2-3rd trimester, then, as a rule, the rest of the pregnancy is completed under the guise of chemotherapy. In addition, breastfeeding must be stopped during chemotherapy courses.

Treatment

When treating myeloid leukemia, the creation of optimal therapeutic tactics requires the cooperation of several specialists. It is especially important that the patient is under the supervision of an oncologist and/or hematologist.

Treatment options depend on several factors, including the phase of the disease, expected side effects, patient preference, and overall health.

Targeted therapy. This is a type of treatment that specifically affects the genes of malignant cells, their proteins and the tissue environment that promotes the growth and survival of leukemia. Targeted therapy blocks the growth and spread of malignant cells while limiting damage to healthy tissue.

The prescription of targeted drugs for AML directly depends on the specificity of the mutations that have arisen in malignant cells. For example, Midostaurin (Rydapt) is indicated for patients with a mutation of the FLT3 gene (25-30% of cases). Enasidenib (IDHIFA) is recommended for people with relapsed or refractory IDH2-mutated AML.

In CML, the target for the active substances is the enzyme tyrosine kinase BCR-ABL. There are 5 main drugs called tyrosine kinase inhibitors (TKIs): Imatinib (Gleevec), Dasatinib (Sprycel), Nilotinib (Tasigna), Bosutinib (Bosulif), and Pontinib (Iclusig). All 5 drugs can stop the BCR-ABL enzyme from working, which causes CML cells to die quickly.

It is important to note that men and women should avoid conceiving while taking TKIs. Otherwise, there is a high risk of spontaneous abortion, intrauterine fetal death, or the birth of a child with severe malformations. In addition, patients may develop idiopathic myelofibrosis as a side effect of CML therapy.

Chemotherapy. Drugs from this group are prescribed to destroy malignant cells by suppressing their ability to grow and divide. The form of drug administration can be in the form of intravenous, subcutaneous injection or in the form of tablets. A chemotherapy regimen usually consists of a specific number of cycles given over a given period of time. The patient can take 1 drug or several at the same time.

This is the main treatment for AML. Due to the frequent development of complications, the treatment process is quite difficult, so chemotherapy courses must be carried out in specialized hospitals. In the treatment of patients, it is customary to distinguish 4 phases:

1. Induction of remission.
2. Consolidation.
3. Intensification.
4. Maintenance therapy (2-5 years).

The most commonly used combination is Cytarabine (Cytosar-U) and an anthracycline drug such as Daunorubicin (Cerubidine) or Idarubicin (idamycin). Some older people cannot take these drugs, and Decitabine (Dacogen), Azacitidine (Vidaza), and/or low-dose Cytarabine may be used instead.

As a rule, 2-5 courses of chemotherapy are necessary to achieve remission, after which the patient enters the consolidation phase and is prescribed several more procedures. Maintenance therapy begins approximately a week after the end of the consolidation period. If modern protocols are followed, stable remission can be achieved in 60%, and recovery in 30% of patients.

As a rule, for CML, hydroxyurea drugs (Droxia, Hydrea) are prescribed, which effectively reduce the number of white blood cells. Chemotherapy can return blood counts to normal within a few days or weeks while reducing the size of the spleen. However, hydroxyurea preparations do not reduce the content of cells with the Philadelphia chromosome and do not have such a pronounced effect in the blast crisis phase. Although hydroxyurea has relatively few side effects, most patients with newly diagnosed CML are recommended to take Imatinib or another TKI. This means that patients do not need hydroxyurea or only use it for a short period.

Stem cell/bone marrow transplantation. This is a medical procedure in which the patient's damaged bone marrow is replaced with hematopoietic stem cells from a healthy donor. The method is considered the most effective way to treat both types of leukemia. There are 2 types of stem cell transplant:

• allogeneic – transplantation from a compatible donor (usually a relative);
• autologous – transplantation of one’s own bone marrow.

The success of transplantation is influenced by the phase of the disease, the results of previous treatment, the patient's age and general condition. Although transplantation is the only method that can guarantee complete recovery in CML, due to the high risk of side effects, it is used less frequently than TKIs.

Immunotherapy. The method enhances the body's natural defense mechanisms to activate them to fight myeloid leukemia. Immunotherapy involves the use of drugs based on immunocomponents produced in laboratory or natural conditions. Interferon (Alferon, Infergen, Intron A, Roferon-A) is an effective group of drugs that can reduce the number of white blood cells, and in some cases even reduce the number of cells containing the Philadelphia chromosome.

Before Imatinib became available, interferon therapy was the mainstay of treatment for chronic phase CML. Currently, Interferon is not recommended as a first-line drug because a number of studies have shown that TKIs work better and cause fewer side effects. Moreover, unlike TKIs, Interferon is safe to take during pregnancy.

New treatment methods. Most major hematology and oncology centers are actively involved in clinical trials aimed at increasing the incidence of successful recovery from myeloid leukemia. When consulting with a doctor, it is necessary to clarify the possibility of participating in research projects to receive experimental treatment.

Promising techniques currently being tested include:

• combinations of Imatinib with other drugs;
• development of new schemes for the use of ITC;
• creation of vaccines against BCR-ABL;
• development of new methods of stem cell transplantation aimed at reducing side effects.

Traditional treatment. Myeloid leukemia is a very serious disease, characterized by high mortality and great difficulty in treatment. For this reason, the use of folk remedies will be ineffective or even harmful for the patient. Patients, if desired, can take decoctions made from pumpkin, blueberries or birch buds, but only in addition to the main treatment.

Rehabilitation

The protocols do not provide for a specific rehabilitation program, but to improve the patient’s well-being, courses of physiotherapy, medicinal baths, oxygen therapy, psychological support and a balanced diet may be recommended. It is important that during the rehabilitation period the patient is under the supervision of a specialist who understands the patient’s condition and knows how to eliminate side effects from therapy.

Relapse

In most cases, patients with acute myeloid leukemia develop a relapse after chemotherapy. In such cases, autologous stem cell transplantation is recommended. A number of hematology centers that adhere to this treatment tactic in the second remission or at the beginning of the first relapse achieve patient recovery in 25-50% of cases.

Such high results were achieved because many patients retained their stem cells during the first remission, after which a successful transplant took place. Harvesting stem cells after relapse is not as effective, as less than half of patients receiving chemotherapy will achieve a second remission. The most optimal solution for patients who do not have previously preserved stem cells is allogeneic transplantation.

If the patient does not have the opportunity to undergo a stem cell transplant, then in such cases the main treatment strategy will be to prescribe high-dose chemotherapy.

Resistant flow

Most patients achieve remission (no signs or symptoms) after initial treatment for AML. But in some patients, small areas of mutated cells remain in the body even after a full course of chemotherapy. Over time, the number of damaged cells will increase until they are detected in tests or until symptoms return. This condition is called resistant leukemia.

After completion of treatment, the doctor must provide the patient with personal information about the possible risk of developing resistant myeloid leukemia.

Complications

Myeloid leukemia has a huge number of complications that develop both during the course of the underlying disease and as a result of taking chemotherapy. However, the greatest concern for doctors, due to the increased risk of death and decreased quality of life, is the following three:

• Due to a pathological increase in the number of immature blast cells, normal blood sprouts are displaced, which leads to disruption of the body's immune mechanisms.

• Bleeding. Due to pathological changes in the blood coagulation system, people with AML are more susceptible to sudden internal bleeding.
• Infertility. Many drugs used in the treatment of AML cause sterility as a side effect. As a rule, it is temporary, but in some cases it can be permanent.

Prognosis (life expectancy)

In AML, the prognosis is determined by the type of cells involved in the pathological process, the age of the patient and the adequacy of the treatment provided. Standard modern therapeutic techniques increase survival in adult patients (up to 60 years), but in older patients this figure is much lower.

The life expectancy of patients suffering from CML does not exceed 3.5 years from the date of diagnosis. The blast crisis phase poses a particular danger to life. It accounts for 85% of all deaths due to CML. Timely and appropriate treatment allows the patient to increase survival by an average of 5-6 years from the moment the disease is diagnosed.

Diet

Patients suffering from blood diseases are prescribed table No. 11. The emphasis in nutrition should be on meat, chicken eggs, milk, cheese and kefir. Also, to replenish the loss of vitamins, regular consumption of vegetables and fruits is necessary. The total daily calorie content should reach at least 4500 kcal.

Prevention

There is no specific prevention of myeloid leukemia. We can only advise people at risk to avoid contact with benzene, pesticides and radioactive elements. One of the goals of follow-up after treatment is to regularly check for relapse. Therefore, it is recommended to undergo an annual preventive examination, which necessarily includes a general blood test.

Treatment of myeloid leukemia in Israel

According to statistics on the treatment of acute myeloid leukemia in Israel, in 90% of cases patients achieve stable remission, and more than half of them end in complete recovery.

In Israeli clinics, therapy for hematological diseases is based on advanced medical technologies, extensive practical experience of specialists and modern protocols that increase patient survival.

Testing for myeloid leukemia is carried out in hematology departments of clinics or in specialized medical centers. Diagnostics include the following:

• Initial examination of the patient and collection of information about the history of the disease, the dynamics of its development and symptoms.
• Laboratory research methods, including hemogram and biochemical blood test. Cytogenetic testing is also performed to identify genetic changes and microscopically evaluate the state of chromosomes in blood cells, bone marrow and lymph nodes.
• A lumbar puncture involves taking bone marrow samples and helps identify the presence of abnormal cells. As a rule, the sampling is made from the lumbar region under local anesthesia using a special puncture needle.
• Bone marrow biopsy is the main method for diagnosing leukemia. It confirms the diagnosis and determines the type of disease. The doctor collects tissue under local anesthesia, or intravenous sedation can be used if the patient wishes.
• Ultrasonography indicates enlarged lymph nodes in the abdominal area, and also allows you to evaluate the structure and size of the liver, spleen and kidneys.

In addition to this diagnostic standard, the doctor may prescribe additional research methods, as well as refer you for consultation to other specialists.

Among the modern treatment methods in Israel, the following are used:

• Chemotherapy aimed at suppressing the growth and division of malignant cells. The technique is based on the principles of increasing efficiency and reducing the risk of side effects.
• A method of monoclonal therapy based on the use of special antibodies that selectively attack atypical cells.
• Stem cell transplantation is the most radical treatment method, which in most cases can completely eliminate the disease.
• Targeted therapy based on the principle of targeting directly at a malignant cell without damaging healthy tissues of the body.

An individual approach to each patient and the use of the latest technologies are the main principles of treatment used in Israeli clinics. Such tactics can significantly increase the patient’s chances of recovery, as well as improve the prognosis for future quality of life.

Best hospitals in Israel

Medical Center "Herzliya". Experienced hematologists guarantee their patients effective treatment for leukemia. Herzliya Private Hospital is Israel's leading medical institution, providing its patients with first-class medical care and the best standards of treatment that can be found. Treatment of hematological diseases at Herzliya Medical Center is based on the latest scientific developments, which allow achieving impressive results at all stages of the disease and meeting the most stringent patient safety standards. The private hospital of the Herzliya Medical Center has all the conditions for diagnosis and treatment of any level of complexity.

Specialists offer their patients modern chemotherapy protocols, bone marrow transplantation, as well as other therapeutic techniques that allow them to achieve maximum results in the treatment of leukemia. The main goal of doctors is to improve the survival rate and quality of life of patients. At the Assuta Clinic, patients receive individualized treatment based on genetic information about the type of hematological pathology. The hospital has a group of experts who are constantly testing new ways to combat leukemia. This means that Assuta Hospital patients can participate in clinical trials of new treatment protocols, which is not available in other hospitals.

Malignant cells can affect any system, organ, or tissue of the body, including the blood. With the development of tumor processes in the myeloid blood lineage, accompanied by intensive proliferation of altered white blood cells, a disease called myeloid leukemia (myeloid leukemia) is diagnosed.

What is myeloid leukemia

The disease is one of the subtypes of leukemia (blood cancer). The development of myeloid leukemia is accompanied by malignant degeneration of immature lymphocytes (blasts) in the red bone marrow. As a result of the spread of mutated lymphocytes throughout the body, the cardiovascular, lymphatic, urinary, and other systems are affected.

Classification (types)

Specialized medical specialists distinguish myeloid leukemia (ICD-10 code - C92), occurring in an atypical form, myeloid sarcoma, chronic, acute (promyelocytic, myelomonocytic, with 11q23 anomaly, with multilineage dysplasia), other myeloid leukemia, unspecified pathological forms .

The acute and chronic stages of progressive myeloid leukemia (unlike many other ailments) do not transform into each other.

Acute myeloid leukemia

Acute myeloid leukemia is characterized by rapid development and active (excessive) growth of blast immature blood cells.

The following stages of acute myeloid leukemia are distinguished:

• Initial. In many cases, it is asymptomatic and is detected during blood biochemistry. Symptoms manifest as exacerbation of chronic diseases.
• Expanded. It is characterized by severe symptoms, periods of remissions and exacerbations. With effectively organized treatment, complete remission is observed. Advanced forms of myeloid leukemia progress to more severe stages.
• Terminal. Accompanied by destabilization of the hematopoietic process.

Chronic myeloid leukemia

Chronic myeloid leukemia (the abbreviation CML is used in the description) is accompanied by intensive growth of leukocyte cells, replacement of healthy bone marrow tissue with connective tissue. Myeloid leukemia is detected mainly in old age. During examinations, one of the stages is diagnosed:

• Benign. Accompanied by an increase in the concentration of leukocytes without deterioration in well-being.
• Accelerative. Signs of the disease are detected, the number of leukocytes continues to increase.
• Blast crisis. It manifests itself as a sharp deterioration in health, low sensitivity to treatment.

If, during the analysis of the clinical picture, it is impossible to accurately determine the nature of the progressive pathology, a diagnosis of “unspecified myeloid leukemia” or “other myeloid leukemia” is made.

Reasons for the development of the disease

Myeloid leukemia is one of the diseases characterized by incompletely studied development mechanisms. Medical professionals use the term “risk factor” when studying potential causes of chronic or acute myeloid leukemia.

An increased likelihood of developing myeloid leukemia is caused by:

• Hereditary (genetic) characteristics.
• Complicated course of Bloom's and Down's syndromes.
• Negative consequences of ionizing radiation.
• Taking courses of radiation therapy.
• Long-term use of certain types of medications.
• Past autoimmune, cancer, infectious diseases.
• Severe forms of tuberculosis, HIV, thrombocytopenia.
• Contacts with aromatic organic solvents.
• Environmental pollution.

Among the factors that provoke myeloid leukemia in children are genetic diseases (mutations), as well as features of the course of pregnancy. Oncological blood disease in a baby can develop due to the harmful effects of radiation and other types of radiation on women during pregnancy, poisoning, smoking, other bad habits, and serious illnesses of the mother.

Symptoms

The predominant symptoms that appear in myeloid leukemia are determined by the stage (severity) of the disease.

Manifestations at the initial stage

Benign myeloid leukemia at the initial stage is not accompanied by severe symptoms and is often discovered by chance during concomitant diagnosis.

Symptoms of the accelerated stage

The acceleration stage manifests itself:

• Loss of appetite.
• Losing weight.
• Elevated temperature.
• Loss of strength.
• Shortness of breath.
• Frequent bleeding.
• Pallor of the skin.
• Hematomas.
• Exacerbations of inflammatory diseases of the nasopharynx.
• Suppuration of skin damage (scratches, wounds).
• Painful sensations in the legs and spine.
• Forced limitation of motor activity, changes in gait.
• Enlarged palatine tonsils.
• Swelling of the gums.
• Increased concentration of uric acid in the blood.

End stage symptoms

The terminal stage of myeloid leukemia is characterized by rapid development of symptoms, deterioration of well-being, and the development of irreversible pathological processes.

Symptoms of myeloid leukemia are supplemented by:

• Numerous hemorrhages.
• Intensification of sweating.
• Rapid weight loss.
• Aching bone and joint pain of varying intensity.
• An increase in temperature to 38-39 degrees.
• Chills.
• Enlarged spleen and liver.
• Frequent exacerbations of infectious diseases.
• Anemia, decrease, appearance of myelocytes, myeloblasts in the blood.
• Formation of necrotic zones on mucous membranes.
• Enlarged lymph nodes.
• Malfunctions in the functioning of the visual system.
• Headaches.

The terminal stage of myeloid leukemia is accompanied by a blast crisis, an increased risk of death.

Features of the course of chronic myeloid leukemia

The chronic stage has the longest duration (on average about 3-4 years) among all stages of the disease. The clinical picture of myeloid leukemia is mostly blurred and does not cause concern for the patient. Over time, the symptoms of the disease worsen, coinciding with the manifestations of the acute form.

The key feature of chronic myeloid leukemia is the lower rate of development of symptoms and complications compared to the rapidly progressing acute form.

How is diagnostics carried out?

Primary diagnosis of myeloid leukemia includes examination, history analysis, assessment of the size of the liver, spleen, and lymph nodes using palpation. In order to study the clinical picture as thoroughly as possible and prescribe effective therapy, specialized medical institutions carry out:

• Detailed blood tests (myeloid leukemia in adults and children is accompanied by an increase in the concentration of leukocytes, the appearance of blasts in the blood, the indicators of erythrocytes and platelets decrease).
• Bone marrow biopsy. During the manipulation, a hollow needle is inserted through the skin into the bone marrow, biomaterial is collected, followed by microscopic examination.
• Spinal tap.
• X-ray examination of the chest.
• Genetic studies of blood, bone marrow, lymph nodes.
• PCR test.
• Immunological examinations.
• Scintigraphy of skeletal bones.
• Tomography (computer, magnetic resonance).

If necessary, the list of diagnostic measures is expanded.

Treatment

Therapy for myeloid leukemia, prescribed after confirmation of the diagnosis, is carried out in the hospital of a medical institution. Treatment methods may vary. The results of previous stages of treatment (if any) are taken into account.

Treatment for chronic myeloid leukemia includes:

• Induction, drug therapy.
• Stem cell transplantation.
• Anti-relapse measures.

Induction therapy

The procedures carried out contribute to the destruction (cessation of growth) of cancer cells. Cytotoxic and cytostatic agents are injected into the cerebrospinal fluid, the foci where the bulk of cancer cells are concentrated. To enhance the effect, polychemotherapy (administration of a group of chemotherapy drugs) is used.

Positive results of induction therapy for myeloid leukemia are observed after completing several treatment courses.

Additional drug therapy methods

Specific treatment with arsenic trioxide, ATRA (trans-retinoic acid) is used in the detection of acute promyelocytic leukemia. Monoclonal antibodies are used to stop the growth and division of leukemic cells.

Stem cell transplant

Transplantation of stem cells responsible for hematopoiesis is an effective method of treating myeloid leukemia, helping to restore the normal functioning of the bone marrow and immune system. The transplant is carried out:

• In an autologous way. Cell collection is carried out from the patient during the remission period. Frozen, processed cells are injected after chemotherapy.
• Allogeneic method. Cells are transplanted from relative donors.

IMPORTANT! The issue of radiation therapy for myeloid leukemia is considered only if the spread of cancer cells to the spinal cord and brain is confirmed.

Anti-relapse measures

The goal of anti-relapse measures is to consolidate the results of chemotherapy, eliminate residual symptoms of myeloid leukemia, and reduce the likelihood of repeated exacerbations (relapses).

As part of the anti-relapse course, drugs are used to improve blood circulation. Maintenance chemotherapy courses are carried out with a reduced dosage of active substances. The duration of anti-relapse treatment for myeloid leukemia is determined individually: from several months to 1-2 years.

To assess the effectiveness of the applied treatment regimens and monitor dynamics, periodic examinations are carried out aimed at identifying cancer cells and determining the degree of tissue damage by myeloid leukemia.

Complications from therapy

Complications from chemotherapy

Patients diagnosed with acute myeloid leukemia are given drugs that damage healthy tissues and organs as part of treatment courses, so the risk of complications is inevitably high.

The list of commonly detected side effects of drug therapy for myeloid leukemia includes:

• Destruction of healthy cells along with cancer cells.
• Weakening of the immune system.
• General malaise.
• Deterioration of hair and skin condition, baldness.
• Loss of appetite.
• Impaired functioning of the digestive system.
• Anemia.
• Increased risk of bleeding.
• Cardiovascular exacerbations.
• Inflammatory diseases of the oral cavity.
• Distortions of taste.
• Destabilization of the functioning of the reproductive system (menstrual irregularities in women, cessation of sperm production in men).

The vast majority of complications of treatment for myeloid leukemia resolve on their own after completion of chemotherapy (or in the intervals between courses). Some subtypes of potent medications can cause infertility and other irreversible consequences.

Complications after bone marrow transplantation

After the transplant procedure, the risk increases:

• Development of bleeding.
• Spread of infection throughout the body.
• Transplant rejection (can occur at any time, even several years after transplantation).

To avoid complications of myeloid leukemia, it is necessary to constantly monitor the condition of patients.

Nutritional Features

Despite the deterioration in appetite observed in chronic and acute myeloid leukemia, it is necessary to adhere to the diet prescribed by a specialist.

To restore strength, meet the needs of the body oppressed by myeloblastic (myeloid) leukemia, and prevent the adverse effects of intensive therapy for leukemia, a balanced diet is necessary.

For myeloid leukemia and other forms of leukemia, it is recommended to supplement:

• Products rich in vitamin C and microelements.
• Greens, vegetables, berries.
• Rice, buckwheat, wheat porridge.
• Sea fish.
• Dairy products (low-fat pasteurized milk, cottage cheese).
• Rabbit meat, offal (kidneys, tongue, liver).
• Propolis, honey.
• Herbal, green tea (has an antioxidant effect).
• Olive oil.

To prevent overload of the digestive tract and other systems in case of myeloid leukemia, the following are excluded from the menu:

• Alcohol.
• Products containing trans fats.
• Fast food.
• Smoked, fried, salty dishes.
• Coffee.
• Baked goods, confectionery products.
• Products that help thin the blood (lemon, viburnum, cranberry, cocoa, garlic, oregano, ginger, paprika, curry).

In case of myeloid leukemia, it is necessary to control the volume of protein food consumption (no more than 2 g per day per 1 kg of body weight), maintain water balance (from 2-2.5 liters of liquid per day).

Life expectancy forecast

Myeloid leukemia is a disease accompanied by an increased risk of death. Life expectancy for acute or chronic myeloid leukemia is determined by:

• The stage at which myeloid leukemia was detected and treatment started.
• Age characteristics, health status.
• Leukocyte level.
• Sensitivity to chemical therapy.
• The intensity of brain damage.
• The duration of the remission period.

With timely treatment and the absence of symptoms of AML complications, the life prognosis for acute myeloid leukemia is favorable: the probability of five-year survival is about 70%. In case of complications, the rate is reduced to 15%. In childhood, the survival rate reaches 90%. If therapy for myeloid leukemia is not carried out, even the 1-year survival rate is low.

The chronic stage of myeloid leukemia, in which systematic treatment measures are carried out, is characterized by a favorable prognosis. For most patients, life expectancy after timely identification of myeloid leukemia exceeds 20 years.

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Diagnosis(CML) in most cases is easy to establish or, in any case, suspect based on characteristic changes in the blood picture. These changes are expressed in a gradually increasing leukocytosis, small at the beginning of the disease (10-15 10 9 / l) and reaching huge numbers as the disease progresses without treatment - 200-500-800 10 9 / l and even more.

Simultaneously with the increase in the number leukocytes characteristic changes in the leukocyte formula are noted: an increase in the content of granulocytes to 85-95%, the presence of immature granulocytes - myelocytes, metamyelocytes, with significant leukocytosis - often promyelocytes, and sometimes single blast cells. A very characteristic increase in the content of basophils to 5-10%, often with a simultaneous increase in the level of eosinophils to 5-8% (“eosinophil-basophil association”, not found in other diseases) and a decrease in the number of lymphocytes to 10-5%.

Sometimes the number of basophils reaches significant figures - 15-20% or more.

In literature 15-20 years ago in such cases, the disease was designated as a basophilic variant of chronic myeloid leukemia, which occurs in 5-8% of patients. An eosinophilic variant has been described, in which there are always 20-40% eosinophils in the blood. Currently, these variants are not isolated, and an increase in the number of basophils or eosinophils is considered a sign of advanced disease.

In most patients, the number of platelets up to 400-600 10 9 / l, and sometimes more - up to 800-1000 10 9 / l, rarely even higher. The content of hemoglobin and red blood cells can remain normal for a long time, decreasing only with very high leukocytosis. In some patients, at the onset of the disease, even a slight erythrocytosis is observed - 5.0-5.5 10 12 l.

Study bone marrow punctate detects an increase in the number of myelokaryocytes and the percentage of immature granulocytes with an increase in the myeloid/erythroid ratio to 20-25/1 instead of the normal 3-4/1. The number of basophils and eosinophils is usually increased, especially in patients with a high content of these cells in the blood. As a rule, a large number of mitotic figures are observed.

In some patients, more often with significant hyperleukocytosis, in the bone marrow punctate blue histiocytes and cells resembling Gaucher cells are found. These are macrophages that take up glucocerebrosides from decaying leukocytes. The number of megakaryocytes is usually increased, as a rule, they have signs of dysplasia.

At morphological study no changes are detected in the structure of granulocytic cells in CML compared to normal ones, however, electron microscopy reveals asynchrony in the maturation of the nucleus and cytoplasm: at each stage of granulocyte maturation, the nucleus lags behind the cytoplasm in its development.

From cytochemical features A sharp decrease or complete disappearance of alkaline phosphatase in neutrophils in the blood and bone marrow is very characteristic.

At trepanobiopsy pronounced hyperplasia of the myeloid germ, a sharp decrease in fat content are detected, in 20-30% of patients already at the onset of the disease there is one or another degree of myelofibrosis.
Morphological study spleen detects infiltration of the red pulp by leukemic cells.

Of the biochemical changes, the characteristic one is increase in vitamin B12 content in blood serum, which sometimes exceeds normal by 10-15 times and often remains elevated during clinical and hematological remission. Another significant change is an increase in uric acid levels. It turns out to be high in almost all untreated patients with significant leukocytosis and can increase even more during cytostatic therapy.

In some patients there is constant increased uric acid levels leads to the formation of urate urinary stones and gouty arthritis, the deposition of uric acid crystals in the tissues of the ears with the formation of visible nodules. The vast majority of patients have high serum lactate dehydrogenase levels.

Start diseases in most cases it is almost or completely asymptomatic. Usually, when changes in the blood have already appeared, the spleen is not enlarged. As the disease progresses, it progressively increases, sometimes reaching enormous sizes. Leukocytosis and spleen size do not always correlate with each other. In some patients, the spleen occupies the entire left half of the abdomen, descending into the small pelvis, with leukocytosis 65-70 10 9 /l, in other patients with leukocytosis reaching 400-500 10 9 /l, the spleen protrudes from under the edge of the costal arch by only 4-5 cm. Large spleen sizes are especially characteristic of CML with high basophilia.

With pronounced splenomegaly The liver is usually enlarged, but always to a much lesser extent than the spleen. Enlarged lymph nodes are not typical for CML; it sometimes occurs in the terminal stage of the disease and is caused by infiltration of the lymph node with blast cells.

Complaints weakness, a feeling of heaviness, sometimes pain in the left hypochondrium, sweating, low-grade fever appear only with a detailed clinical and hematological picture of the disease.

U 20-25% of patients with CML It is detected by chance, when there are still no clinical signs of the disease, and there are only mildly expressed hematological changes (leukocytosis and a small percentage of immature granulocytes in the blood), which are detected during a blood test done for another disease or during a preventive examination. The absence of complaints and clinical symptoms sometimes leads to the fact that characteristic but moderate changes in the blood, unfortunately, do not attract the doctor’s attention, and the true onset of the disease can only be established retrospectively when a patient presents with an already pronounced clinical and hematological picture of the disease.

Confirmation diagnosis of CML is the detection in blood and bone marrow cells of a characteristic cytogenetic marker - the Ph chromosome. This marker is present in all patients with CML and is not found in other diseases.

Chronic myeloid leukemia- the first oncological disease in which specific changes in chromosomes were described in humans and the molecular mechanisms underlying the development of the disease were deciphered.

In 1960 two cytogenetics from Philadelphia in the USA, P. Nowell and D. Hungerford found a shortening of the long arm of one of the chromosomes of the 21st pair in all the CML patients they examined. Based on the name of the city where the discovery was made, this chromosome was called the Philadelphia, or Ph-chromosome. In 1970, using a more advanced chromosome staining technique, T. Caspersson et al. They found that in CML there is a deletion of the long arm of one of the chromosomes, not the 21st, but the 22nd pair. Finally, in 1973, a major discovery was made, which became the starting point in the study of the pathogenesis of CML: J. Rowley showed that the formation of the Ph chromosome is due to reciprocal translocation (mutual exchange of part of the genetic material) between chromosomes 9 and 22.

With such translocations Most of the long arm of chromosome 22 is transferred to the long arm of chromosome 9, and a small terminal part of the long arm of chromosome 9 is transferred to chromosome 22. As a result, a characteristic cytogenetic anomaly occurs - elongation of the long arm of one of the chromosomes of the 9th pair and shortening of the long arm of one of the chromosomes of the 22nd pair. It is this chromosome from the 22nd pair with a shortened long arm that is designated as the Ph chromosome.

It has now been established that Ph chromosome- t(9;22)(q34;q11) is found in 95-100% of metaphases in 90-95% of CML patients. In approximately 5% of cases, variant forms of the Ph chromosome are detected. Most often these are complex translocations involving chromosomes 9, 22 and some third chromosome, and sometimes additional 2 or 3 chromosomes. With complex translocations there are always the same molecular changes as with the standard t(9;22)(q34;q11). Standard and variant translocations can be simultaneously detected in the same patient in different metaphases.

Sometimes there is a so-called masked translocation with the same molecular changes as in typical cases, but not determined by conventional cytogenetic methods. This is due to the transfer of smaller chromosome sections than during standard translocation. There are also cases described when t(9; 22) is not detected during a conventional cytogenetic study, but using FISH or RT-PCR (real-time PCR) it is possible to establish that in a typical region of chromosome 22 there is a gene rearrangement that is standard for CML - the formation chimeric gene BCR-ABL. Studies of such cases have shown that sometimes there is a transfer of a region of chromosome 9 to chromosome 22, but there is no translocation of a region of chromosome 22 to chromosome 9.

In the initial period cytogenetic study of chronic myeloid leukemia There were two variants of it: Ph-positive and Ph-negative. Ph-negative CML was first described by S. Krauss et al. in 1964. The authors found Ph-negative CML in almost half of the patients they observed. Subsequently, as research methods improved, the proportion of Ph-negative CML steadily decreased. It is now recognized that true Ph-negative (BCR-ABL-negative) CML does not exist, and previously described observations in most cases were related to BCR-ABL-positive CML, but with a type of chromosomal rearrangement that could not be detected by known at that time using cytogenetic methods.

Thus, received to present time data suggest that in all cases of CML there are changes in chromosomes 9 and 22 with the same rearrangement of genes in a certain region of chromosome 22. In cases where characteristic cytogenetic changes cannot be detected, we are talking about other diseases similar to CML in clinical manifestations (splenomegaly) and blood picture (hyperleukocytosis, neutrophilia). Most often, this is chronic myelomonocytic leukemia (CMML), which in the 2001 WHO classification refers to diseases that have both myeloproliferative and myelodysplastic features. In CMML, the number of monocytes in the blood and bone marrow is always increased.

With chronic myeloid leukemia, many patients have translocations involving chromosome 5: t(5;7), t(5;10), t(5;12), in which fusion genes are formed involving the PDGFbR gene located on chromosome 5 (gene for the b-receptor of growth factor produced by platelets, - platelet-derived growth factor receptor b). The protein produced by this gene has a domain with the function of tyrosine kinase, which is activated during translocation, which often causes significant leukocytosis.

In the presence of leukocytosis, neutrophilia and young forms of granulocytes in the blood, dysplasia of all myelopoiesis sprouts, but the absence of monocytosis, the disease, according to the WHO classification, is designated as atypical CML, also considered under the heading of myelodysplastic/myeloproliferative diseases. In 25-40% of cases, this disease, like other forms of myelodysplastic syndromes, ends in acute leukemia. No characteristic cytogenetic changes are detected.